110 results on '"Barbare JC"'
Search Results
2. Is bleeding time measurement useful for choosing the liver biopsy route? The results of a pragmatic, prospective multicentric study in 219 patients
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Bonnard, P Vitte, RL Barbare, JC Denis, J Stepani, P and Di Martino, V Coutarel, P Eugene, C Van Batten, C and Cadranel, JF
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- 1999
3. Prise en charge de l'hémorragie digestive liée l'hypertension portale au cours de la cirrhose: Evaluation de la conférence de consensus de Paris
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Charpignon, C, primary, Oberti, F, additional, Bernard, P, additional, Bartoli, E, additional, Pauwels, A, additional, Renard, P, additional, Cadranel, JF, additional, Bernard-Chabert, B, additional, Barbare, JC, additional, Ingrand, I, additional, and Beauchant, M, additional
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- 2006
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4. Prise en charge de l'hémorragie digestive liée à l'hypertension portale au cours de la cirrhose: résultats d'une enquête multicentrique
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Beauchant, M, primary, Gournay, J, additional, Bernard, P, additional, Oberti, F, additional, Bernard-Chabert, B, additional, Pauwels, A, additional, Renard, P, additional, Bartoli, E, additional, Cadranel, JF, additional, Barbare, JC, additional, and Ingrand, I, additional
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- 2005
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5. Prognostic value of caffeine plasma clearance in cirrhotic patients
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Barbare, JC., primary, Bories, C., additional, Cadranel, JF., additional, Lévy, P., additional, Capron, JP., additional, Stépani, P., additional, Latrive, JP, additional, and Capron, D., additional
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- 1998
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6. Prevalence and risk factors of urinary tract infection in cirrhotics: A prospective case-control multicentric study
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Cadranel, JF, primary, Denis, J, additional, Barbare, JC, additional, Medini, A, additional, Eugène, C, additional, Poquet, E, additional, Latrive, JP, additional, Pauwels, A, additional, and Devergie, B, additional
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- 1995
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7. Treatment of severe alcoholic hepatitis by infusion of insulin and glucagon. A multicentre sequential trial
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Trienchet, JC, primary, Balkau, B, additional, Heintzmann, F, additional, Poupon, RE, additional, Callard, P, additional, Gotheil, C, additional, Grangé, JD, additional, Vetter, D, additional, Pauwels, A, additional, Labadie, H, additional, Chazouillères, O, additional, Mavier, P, additional, Desmorat, H, additional, Zarsky, JP, additional, Barbare, JC, additional, Chambre, JF, additional, Pariente, EA, additional, Roulot, D, additional, and Beaugrand, M, additional
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- 1990
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8. Early surgery for failure after chemoradiation in operable thoracic oesophageal cancer. Analysis of the non-randomised patients in FFCD 9102 phase III trial: Chemoradiation followed by surgery versus chemoradiation alone
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Julie, Vincent, Christophe, Mariette, Denis, Pezet, Emmanuel, Huet, Franck, Bonnetain, Olivier, Bouché, Thierry, Conroy, Bernard, Roullet, Jean-François, Seitz, Jean-Philippe, Herr, Frédéric, Di Fiore, Jean-Louis, Jouve, Laurent, Bedenne, M, Ducreux, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Claude Huriez [Lille], CHU Lille, CHU Clermont-Ferrand, Nutrition, inflammation et dysfonctionnement de l'axe intestin-cerveau (ADEN), Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Normandie Université (NU), Institute for Research and Innovation in Biomedicine (IRIB), Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de chirurgie digestive [CHU Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Fédération Francophone de la Cancérologie Digestive, FFCD, Hôpital Robert Debré, Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims (CHU Reims), Maladies chroniques, santé perçue, et processus d'adaptation (APEMAC), Université Paris Descartes - Paris 5 (UPD5)-Université de Lorraine (UL), Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Hôpital de la Milétrie, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital privé Sainte-Marie - Ramsay Générale de Santé, Hôpital Charles Nicolle [Rouen], Butel J, Desselle P, Brice JC, Tissot B, Votte-Lambert A, Joly J, Burtin P, Arnaud JP, Cellier P, Estermann F, Chauvet B, Maringe E, Ozanne F, Varlet F, Becouarn Y, Avril A, Rougier P, Nordlinger B, Vincendet M, Charneau J, Pillon D, Stremsdoerfer N, Pelletier M, Clavero-Fabri MC, Leduc B, Segol P, Argouach LP, Roussel A, Maurel J, Salame R, Lacourt J, Janoray P, Ruget O, Baudet-Klepping D, Dupont G, Bommelaer G, Ruszniewski P, Hammel P, Chaussade S, Dousset B, Denis B, Wagner JD, Tamby E, Petit T, Weiss AM, Barbare JC, Jouve JL, Phelip JM, Senesse P, Michiels C, Maingon P, Coudert B, Fraisse J, Queuniet A, Gasnault L, Gstach JH, Guichard B, Howaizi M, Geoffroy P, Picot C, Fournet J, Mousseau M, Stampfli C, Michel P, Doll J, Durand S, Buffet C, Triboulet JP, Denimal F, Hebbar M, Quandalle P, Mirabel X, Lledo G, Giovannini M, Souillac P, Untereiner M, Leroy-Terquem E, Lacroix H, Francois E, Lagasse JP, Breteau N, Legoux JL, Etienne JC, Delattre JF, Lubrano D, Levy-Chazal N, Palot JP, Nasca S, Demange L, Nguyen TD, Seng S, Michel P, Teniere P, Thevenet P, Le Brise H, Fleury J, Kammerer J, Cosme H, Novello P, Avignon JP, Berton C, Legueul, Parisot P, Aunis G, Vetter D, Platini C, Cals L, Rouhier D, Robin B, Champetier T, Cartalat A, Marchal C, Guillemin F, Flamenbaum M, Cassan D, Ducreux M., Hôpital Claude Huriez, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU - HÔTEL-DIEU Clermont-Ferrand, Service de chirurgie digestive [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ), Hôpital Robert Debré-Centre Hospitalier Universitaire de Reims ( CHU Reims ), Maladies chroniques, santé perçue, et processus d'adaptation. Approches épidémiologiques et psychologiques. ( APEMAC - EA 4360 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Université de Lorraine ( UL ), Institut de Cancérologie de Lorraine - Alexis Vautrin ( ICL ), CHU de Poitiers, and Hôpital de la Timone [CHU - APHM] ( TIMONE )
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Male ,Cancer Research ,Time Factors ,Esophageal Neoplasms ,Kaplan-Meier Estimate ,MESH: Esophagectomy ,law.invention ,MESH: Proportional Hazards Models ,MESH : Adenocarcinoma ,0302 clinical medicine ,Randomized controlled trial ,law ,Risk Factors ,MESH : Esophagectomy ,MESH: Risk Factors ,MESH : Neoplasm Staging ,MESH : Female ,MESH : Carcinoma, Squamous Cell ,MESH: Treatment Outcome ,MESH: Chemoradiotherapy ,Randomised controlled trial ,education.field_of_study ,Hazard ratio ,[ SDV.SPEE ] Life Sciences [q-bio]/Santé publique et épidémiologie ,MESH: Carcinoma, Squamous Cell ,Chemoradiotherapy ,MESH : Chemoradiotherapy ,MESH: Neoplasm Staging ,MESH : Risk Factors ,Neoadjuvant Therapy ,3. Good health ,Oesophageal neoplasms ,Treatment Outcome ,Oncology ,Chemoradiation ,030220 oncology & carcinogenesis ,MESH: Esophageal Neoplasms ,Carcinoma, Squamous Cell ,030211 gastroenterology & hepatology ,Female ,Esophageal Squamous Cell Carcinoma ,France ,MESH : Time Factors ,medicine.medical_specialty ,MESH: Radiotherapy, Adjuvant ,MESH : Male ,Population ,MESH: Neoadjuvant Therapy ,Locally advanced ,MESH : Treatment Outcome ,Adenocarcinoma ,MESH : Radiotherapy, Adjuvant ,MESH : Kaplan-Meier Estimate ,03 medical and health sciences ,Early surgery ,medicine ,Humans ,Basal cell ,Salvage surgery ,education ,MESH : France ,Contraindication ,MESH: Kaplan-Meier Estimate ,Neoplasm Staging ,Proportional Hazards Models ,MESH: Humans ,business.industry ,MESH : Humans ,MESH: Adenocarcinoma ,MESH: Time Factors ,Cancer ,medicine.disease ,MESH : Proportional Hazards Models ,MESH: Male ,Surgery ,Esophagectomy ,MESH: France ,Radiotherapy, Adjuvant ,[SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie ,MESH : Esophageal Neoplasms ,business ,MESH : Neoadjuvant Therapy ,MESH: Female - Abstract
International audience; BACKGROUND:Two randomised trials concerning thoracic oesophageal cancer concluded that for squamous cell carcinoma, chemoradiation alone leads to the same overall survival (OS) as chemoradiation followed by surgery. One of these trials, FFCD 9102, randomised only fit, compliant and operable responders to induction chemoradiation between continuation of chemoradiation and surgery. In the present analysis, the outcome in the patients not eligible for randomisation was calculated to determine if attempt of surgery should be recommended.METHODS:Eligible patients had operable T3-N0/N1-M0 thoracic oesophageal cancer. After initial chemoradiation, patients with no clinical response, or with contraindication to follow any attributed treatment, were not randomised. OS was studied first in the whole population of not randomised patients, and then specifically in clinical non-responders. The impact of surgery on OS was studied in these two populations.FINDINGS:Of the 451 registered patients in the trial, 192 were not randomised. Among them, 111 were clinical non-responders. Median OS was significantly shorter for non-randomised patients (11.5 months) than for randomised patients (18.9 months; p=0.0024). However, for the 112 non-randomised patients who underwent surgery, median OS was not different from that in randomised patients: 17.3 versus 18.9 months (p=0.58). Concerning clinical non-responders, median OS was longer for those who underwent surgery compared to non-operated patients: 17.0 versus 5.5 months (hazard ratio (HR)=0.39 [0.25-0.61]; p
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- 2015
9. Hepatocellular carcinoma: French Intergroup Clinical Practice Guidelines for diagnosis, treatment and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO, AFEF, SIAD, SFR/FRI).
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Blanc JF, Debaillon-Vesque A, Roth G, Barbare JC, Baumann AS, Boige V, Boudjema K, Bouattour M, Crehange G, Dauvois B, Decaens T, Dewaele F, Farges O, Guiu B, Hollebecque A, Merle P, Selves J, Aparicio T, Ruiz I, and Bouché O
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- Combined Modality Therapy, Follow-Up Studies, Humans, Societies, Medical, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular therapy, Liver Neoplasms diagnosis, Liver Neoplasms therapy
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Introduction: This document is a summary of the French Intergroup guidelines regarding the management of hepatocellular carcinoma (HCC) published in March 2019., Method: It is a collaborative work under the auspices of most of the French medical societies involved in the management of HCC. It is based on the previous guidelines published in 2017. Recommendations are graded in 3 categories according to the level of evidence of data found in the literature., Results: The diagnosis and staging of HCC is essentially based on clinical, biological and imaging features. A pathological analysis obtained by a biopsy of tumoral and non-tumoral liver is recommended. HCCs can be divided into 2 groups, taking into account not only the tumor stage, but also liver function. HCCs accessible to curative treatments are tumors that are in Milan criteria or with an AFP score ≤ 2, mainly treated by surgical resection, local ablation or liver transplantation. Intermediate and advanced HCCs with no liver insufficiency, accessible only to palliative treatments, benefit from TACE, SIRT or systemic therapy according to the presence or absence of macrovascular invasion or extrahepatic spread., Conclusion: Such recommendations are in permanent optimization and each individual case must be discussed in a multidisciplinary expert board., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)
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- 2021
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10. Geographical Disparities of Outcomes of Hepatocellular Carcinoma in France: The Heavier Burden of Alcohol Compared to Hepatitis C.
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Costentin CE, Sogni P, Falissard B, Barbare JC, Bendersky N, Farges O, and Goutte N
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- Aged, Aged, 80 and over, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular mortality, Databases, Factual, Female, France epidemiology, Hepatitis C diagnosis, Hepatitis C mortality, Hepatitis, Alcoholic diagnosis, Hepatitis, Alcoholic mortality, Humans, Incidence, Liver Neoplasms diagnosis, Liver Neoplasms mortality, Male, Middle Aged, Retrospective Studies, Risk Assessment, Risk Factors, Treatment Outcome, Carcinoma, Hepatocellular therapy, Health Status Disparities, Healthcare Disparities, Hepatitis C therapy, Hepatitis, Alcoholic therapy, Liver Neoplasms therapy
- Abstract
Background: Data on alcohol-related HCC are limited., Aims: Our aim was to describe the incidence, management, and prognosis of alcohol compared to Hepatitis C (HCV)-related HCC at a national level., Methods: Incident cases of HCC were identified in French healthcare databases between 2009 and 2012 and analyzed retrospectively. Demographic data, type, location, and annual HCC-caseload of the hospitals where patients were first managed were retrieved. Survival of incident cases was computed from the time of diagnosis and adjusted for potential confounding variables., Results: The study population included 14,060 incident cases of alcohol and 2581 HCV-related HCC. Alcohol-related HCC was more frequent than HCV-related HCC (29.37 and 5.39/100,000 adults/year, respectively) with an heterogeneous distribution on the French territory. The optimal treatment was less frequently curative (20.5% vs 35.9%; p < 0.001), and survival was significantly shorter (9.5 [9.0-10.0] versus 16.8 [15.5-18.7] months p < 0.001) in alcohol compared to HCV-related HCC, with marked variations between regions for a given risk factor. In multivariable analysis in the whole study population, curative treatment was a strong predictor of survival (adjusted HR 0.28 [0.27-0.30] months p < 0.001). Being managed at least once in a teaching hospital during follow-up was independently associated with receiving a curative treatment and survival., Conclusion: In France, incidence of alcohol-related HCC is high and prognosis is poor compared to HCV-related HCC, with marked variations between regions. These results should guide future health policy initiatives pertaining to HCC care. Importantly, increasing patient' referral in expert centers could increase chances to receive curative treatment and improve outcomes.
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- 2020
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11. Idarubicin-loaded Beads for Chemoembolization of Hepatocellular Carcinoma: The IDASPHERE II Single-Arm Phase II Trial.
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Guiu B, Chevallier P, Assenat E, Barbier E, Merle P, Bouvier A, Dumortier J, Nguyen-Khac E, Gugenheim J, Rode A, Oberti F, Valette PJ, Yzet T, Chevallier O, Barbare JC, Latournerie M, and Boulin M
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- Aged, Aged, 80 and over, Antibiotics, Antineoplastic administration & dosage, Antibiotics, Antineoplastic adverse effects, Female, Humans, Idarubicin administration & dosage, Idarubicin adverse effects, Male, Middle Aged, Antibiotics, Antineoplastic therapeutic use, Carcinoma, Hepatocellular therapy, Chemoembolization, Therapeutic methods, Idarubicin therapeutic use, Liver Neoplasms therapy
- Abstract
Background A prior in vitro study showed that idarubicin was the most cytotoxic agent for hepatocellular carcinoma (HCC) cell lines. Idarubicin-loaded beads for transarterial chemoembolization (TACE) were previously evaluated for the appropriate dose in a phase I dose-escalation study. Purpose To evaluate objective response rate (ORR), safety, and survival after TACE by using idarubicin-loaded beads for unresectable HCC. Materials and Methods This prospective single-arm phase II study was conducted between January 2015 and January 2017. Participants with unresectable HCC were included in the trial and underwent TACE with idarubicin-eluting beads. The primary end point was 6-month ORR assessed with independent central review by using modified Response Evaluation Criteria in Solid Tumors. Secondary end points were best ORR during the first 6 months, overall survival, progression-free survival, time to progression, and safety. A two-stage Fleming statistical design was used. Results Forty-six study participants (mean age, 71.2 years ± 10.2; six women and 40 men) were included; 44 participants underwent at least one TACE session. The 6-month ORR was 52% (23 of 44). The best ORR achieved was 68% (30 of 44). Fourteen of 44 (32%) participants underwent a curative treatment after TACE. Median progression-free survival, time to progression, and overall survival were 6.6 months, 9.5 months, and 18.6 months, respectively. TACE was discontinued for toxicity in four of 44 (9%) participants. The most frequent grade 3-4 adverse events were elevated aspartate aminotransferase (14 of 44, 32%), elevated γ-glutamyl transpeptidase (eight of 44, 18%), hyperbilirubinemia (seven of 44, 16%), elevated alanine aminotransferase (seven of 44, 16%), and pain (seven of 44, 16%). Conclusion Idarubicin-eluting beads showed a good safety profile and promising objective response rate and time to progression when used as part of a transarterial chemoembolization regimen for unresectable hepatocellular carcinoma. © RSNA, 2019 See also the editorial by Padia in this issue.
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- 2019
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12. Early decrease in serum amphiregulin or vascular endothelial growth factor levels predicts sorafenib efficacy in hepatocellular carcinoma.
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Godin C, Bodeau S, Saidak Z, Louandre C, François C, Barbare JC, Coriat R, Galmiche A, and Sauzay C
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- Carcinoma, Hepatocellular blood, Carcinoma, Hepatocellular mortality, Cell Line, Tumor, Enzyme-Linked Immunosorbent Assay, Female, Humans, Kaplan-Meier Estimate, Liver Neoplasms blood, Liver Neoplasms mortality, Male, Middle Aged, Prognosis, Progression-Free Survival, Time Factors, Treatment Outcome, Amphiregulin blood, Antineoplastic Agents therapeutic use, Biomarkers, Tumor blood, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Sorafenib therapeutic use, Vascular Endothelial Growth Factor A blood
- Abstract
Sorafenib is the standard of care for the treatment of advanced hepatocellular carcinoma (HCC). However, identifying secreted biomarkers that predict sorafenib efficacy in all HCC patients remains challenging. It was recently reported that sorafenib interferes with protein homeostasis and inhibits global translation in tumour cells. A likely consequence of this inhibition would be the interruption of autocrine loops. The aim of the present study was to investigate the effect of sorafenib on two growth factors implicated in autocrine loops and HCC tumour invasion: amphiregulin (AREG) and vascular endothelial growth factor (VEGF). ELISA, quantitative polymerase chain reaction analysis, western blotting and a cytokine array were performed on HCC cell lines and the prognostic role of these two biomarkers in HCC patients was evaluated. Serum AREG and VEGF levels were assayed by ELISA in 55 patients with advanced HCC treated with sorafenib. It was observed that sorafenib decreased AREG, VEGF and cytokine expression at the transcriptional and post‑transcriptional levels. All HCC patients in our cohort had detectable concentrations of AREG and VEGF both at baseline and after sorafenib treatment. The decreased serum levels of AREG and VEGF after 15 days of sorafenib treatment were significantly associated with better overall and progression‑free survival. The results of the multivariate analysis demonstrated that a decrease in AREG was an independent prognostic indicator of overall survival (hazard ratio, 0.208; 95% confidence interval, 0.173‑0.673; P=0.0003). These results suggest that sorafenib inhibits auto-crine loops and that early decrease in serum AREG or VEGF levels predicts sorafenib efficacy in HCC patients.
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- 2019
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13. [Care pathway of patients with hepatocellular carcinoma in France: State of play in 2017].
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Costentin C, Ganne-Carrié N, Rousseau B, Gérolami R, and Barbare JC
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- Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular pathology, Carcinoma, Hepatocellular therapy, Early Detection of Cancer, France, Humans, Liver Neoplasms mortality, Liver Neoplasms therapy, Prognosis, Time Factors, Carcinoma, Hepatocellular diagnosis, Critical Pathways, Liver Neoplasms diagnosis, Neoplasm Staging
- Abstract
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.)
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- 2017
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14. Geographical variations in incidence, management and survival of hepatocellular carcinoma in a Western country.
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Goutté N, Sogni P, Bendersky N, Barbare JC, Falissard B, and Farges O
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- Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular therapy, Databases, Factual, Female, France epidemiology, Humans, Incidence, Kaplan-Meier Estimate, Liver Neoplasms mortality, Liver Neoplasms therapy, Male, Middle Aged, Carcinoma, Hepatocellular epidemiology, Liver Neoplasms epidemiology
- Abstract
Background & Aims: Information on the incidence, management, and prognosis of hepatocellular carcinoma (HCC) is derived from population samples, regional data, or registries. Comprehensive national evaluations within a given country are lacking. This study aimed to investigate regional variations in HCC care within France., Methods: This observational study analysed data from French administrative databases for more than 30,000 patients with HCC diagnosed between 2009 and 2012, and followed-up until 2013. The incidence of HCC, access to surgery, and survival, at both the national level and two geographical levels (the 21 French regions and 95 French departments into which France is divided administratively), were determined. The influence on outcome of the structure of the hospital where HCC was first managed was assessed., Results: At the national level, the median survival was 9.4months and only 22.8% of patients had curative treatment. There were marked variations between regions and departments in incidence, access to curative treatment (range 1.3-28.8% and 8.1-32.3% respectively), and in median survival (range 5.7-12.1 and 4.3-16.5months respectively). The administrative type and annual HCC-caseload of the hospital where patients were first admitted also had an independent influence on treatment and survival., Conclusion: Despite full insurance coverage for all citizens, national measures to reduce inequities in the management of cancer patients, standardised recommendations for HCC surveillance and management, the percentage of patients undergoing curative treatment and their survival may vary four-fold depending on their postcode. The hospital in which patients are first managed has a clear influence on accessibility to both good care and survival., Lay Summary: Population-based studies have highlighted large and sometimes unexpected differences between countries in the survival of patients with malignancy. As these differences are considered to indicate the overall effectiveness of health systems, in addition to the incidence of the cancer or quality of registration, variations within a given country should be minimal. However, similar to between countries differences, this study shows differences within the same country in the incidence, curative treatment rate, and survival of patients with HCC. Evidence that access to care and survival varies within a country can strengthen the impetus for government and clinicians to address these disparities., (Copyright © 2016 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
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- 2017
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15. Alpha-foetoprotein (AFP): A multi-purpose marker in hepatocellular carcinoma.
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Sauzay C, Petit A, Bourgeois AM, Barbare JC, Chauffert B, Galmiche A, and Houessinon A
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- Biomarkers, Tumor analysis, Carcinoma, Hepatocellular diagnosis, Humans, Liver Neoplasms diagnosis, alpha-Fetoproteins analysis, Biomarkers, Tumor metabolism, Carcinoma, Hepatocellular metabolism, Liver Neoplasms metabolism, alpha-Fetoproteins metabolism
- Abstract
Alpha-foetoprotein (AFP), one of the first protein tumour markers discovered, is widely used today in clinical practice. Its application for the screening and diagnosis of hepatocellular carcinoma (HCC), the most frequent form of primary liver tumour, is a matter of extensive debate. In addition to the studies focused on the role of the AFP in the diagnosis of HCC, in recent years AFP has been used to guide the therapeutic choice in HCC and monitor the treatment. Here, we summarize the latest studies that show the interest of AFP quantification in determining the suitability of liver transplantation or to follow-up on patients receiving the targeted treatment sorafenib. We also highlight the recent studies showing the active role of AFP in tumour progression, and the new modes of regulation of this tumour marker. Among these is the regulation of AFP through tumour proteostasis and the Unfolded Protein Response (UPR). We discuss the implications of this new knowledge in the therapeutic context, in terms of interpreting serum levels of AFP, and the new perspectives offered by AFP for the study of tumour proteostasis., (Copyright © 2016 Elsevier B.V. All rights reserved.)
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- 2016
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16. Metallothionein-1 as a biomarker of altered redox metabolism in hepatocellular carcinoma cells exposed to sorafenib.
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Houessinon A, François C, Sauzay C, Louandre C, Mongelard G, Godin C, Bodeau S, Takahashi S, Saidak Z, Gutierrez L, Régimbeau JM, Barget N, Barbare JC, Ganne N, Chauffert B, Coriat R, and Galmiche A
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- Biomarkers, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular genetics, Carcinoma, Hepatocellular mortality, Cell Line, Tumor, Cysteine metabolism, Gene Expression Regulation, Neoplastic drug effects, Humans, Liver Neoplasms drug therapy, Liver Neoplasms genetics, Liver Neoplasms mortality, Metallothionein genetics, NF-E2-Related Factor 2 metabolism, Niacinamide pharmacology, Oxidative Stress, Prognosis, Promoter Regions, Genetic, Sorafenib, Transcription, Genetic, Antineoplastic Agents pharmacology, Carcinoma, Hepatocellular metabolism, Liver Neoplasms metabolism, Metallothionein metabolism, Niacinamide analogs & derivatives, Oxidation-Reduction drug effects, Phenylurea Compounds pharmacology, Protein Kinase Inhibitors pharmacology
- Abstract
Background: Sorafenib, a kinase inhibitor active against various solid tumours, induces oxidative stress and ferroptosis, a new form of oxidative necrosis, in some cancer cells. Clinically-applicable biomarkers that reflect the impact of sorafenib on the redox metabolism of cancer cells are lacking., Methods: We used gene expression microarrays, real-time PCR, immunoblot, protein-specific ELISA, and gene reporter constructs encoding the enzyme luciferase to study the response of a panel of cancer cells to sorafenib. Tumour explants prepared from surgical hepatocellular carcinoma (HCC) samples and serum samples obtained from HCC patients receiving sorafenib were also used., Results: We observed that genes of the metallothionein-1 (MT1) family are induced in the HCC cell line Huh7 exposed to sorafenib. Sorafenib increased the expression of MT1G mRNA in a panel of human cancer cells, an effect that was not observed with eight other clinically-approved kinase inhibitors. We identified the minimal region of the MT1G promoter that confers inducibility by sorafenib to a 133 base pair region containing an Anti-oxidant Response Element (ARE) and showed the essential role of the transcription factor NRF2 (Nuclear factor erythroid 2-Related Factor 2). We examined the clinical relevance of our findings by analysing the regulation of MT1G in five tumour explants prepared from surgical HCC samples. Finally, we showed that the protein levels of MT1 increase in the serum of some HCC patients receiving sorafenib, and found an association with reduced overall survival., Conclusion: These findings indicate that MT1 constitute a biomarker adapted for exploring the impact of sorafenib on the redox metabolism of cancer cells.
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- 2016
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17. Alpha-fetoprotein is a biomarker of unfolded protein response and altered proteostasis in hepatocellular carcinoma cells exposed to sorafenib.
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Houessinon A, Gicquel A, Bochereau F, Louandre C, Nyga R, Godin C, Degonville J, Fournier E, Saidak Z, Drullion C, Barbare JC, Chauffert B, François C, Pluquet O, and Galmiche A
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- Biomarkers, Carcinoma, Hepatocellular metabolism, Cell Line, Tumor, Cell Survival drug effects, DNA-Binding Proteins physiology, Humans, Liver Neoplasms metabolism, Niacinamide pharmacology, Regulatory Factor X Transcription Factors, Sorafenib, Transcription Factors physiology, alpha-Fetoproteins biosynthesis, Antineoplastic Agents pharmacology, Carcinoma, Hepatocellular drug therapy, Homeostasis, Liver Neoplasms drug therapy, Niacinamide analogs & derivatives, Phenylurea Compounds pharmacology, Proteins metabolism, Unfolded Protein Response, alpha-Fetoproteins analysis
- Abstract
Sorafenib is the treatment of reference for advanced hepatocellular carcinoma (HCC). A decrease in the serum levels of Alpha-fetoprotein (AFP) is reported to be the biological parameter that is best associated with disease control by sorafenib. In order to provide a biological rationale for the variations of AFP, we analyzed the various steps of AFP production in human HCC cell lines exposed to sorafenib. Sorafenib dramatically reduced the levels of AFP produced by HCC cells independently of its effect on cell viability. The mRNA levels of AFP decreased upon sorafenib treatment, while the AFP protein remained localized in the Golgi apparatus. Sorafenib activated the Regulated Inositol-Requiring Enzyme-1α (IRE-1α) and the PKR-like ER Kinase (PERK)-dependent arms of the Unfolded Protein Response (UPR). The inhibition of IRE-1α partially restored the mRNA levels of AFP upon treatment with sorafenib. The inhibition of both pathways partially prevented the drop in the production of AFP induced by sorafenib. The findings provide new insights on the regulation of AFP, and identify it as a biomarker suitable for the exploration of HCC cell proteostasis in the context of therapeutic targeting., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2016
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18. The endless SEARCH for a better medical treatment of advanced hepatocellular carcinoma.
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Galmiche A, Diouf M, and Barbare JC
- Subjects
- Female, Humans, Male, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Niacinamide analogs & derivatives, Phenylurea Compounds therapeutic use
- Published
- 2015
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19. Biomarkers of apoptosis and necrosis in patients with hepatocellular carcinoma treated with sorafenib.
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Godin C, Louandre C, Bodeau S, Diouf M, Saidak Z, Conte MA, Chauffert B, Barbare JC, Barget N, Trinchet JC, Ganne N, and Galmiche A
- Subjects
- Aged, Apoptosis, Biomarkers, Carcinoma, Hepatocellular blood, Carcinoma, Hepatocellular pathology, Female, Humans, Keratin-18 blood, Liver Neoplasms blood, Liver Neoplasms pathology, Male, Necrosis, Niacinamide blood, Niacinamide therapeutic use, Phenylurea Compounds blood, Sorafenib, Antineoplastic Agents therapeutic use, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Niacinamide analogs & derivatives, Phenylurea Compounds therapeutic use, Receptors, Vascular Endothelial Growth Factor antagonists & inhibitors
- Abstract
Background/aim: Sorafenib is the medical reference for treatment of hepatocellular carcinoma (HCC). Multiple forms of cytotoxicity are induced by sorafenib in HCC cells in vitro but it is unclear what extent of apoptosis and necrosis is induced in HCC patients receiving sorafenib., Patients and Methods: The M30 and M65 biomarkers, which reflect the release of cytokeratin-18 and its apoptotic cleavage fragments, were measured in patients with HCC (n=36) and matched patients with cirrhosis (n=47). A serum sample was collected from 20 patients with HCC four weeks after the onset of treatment with sorafenib., Results: Basal serum levels of M30 and M65 were increased in patients with HCC compared to those with uncomplicated cirrhosis. No statistically significant increase in the level of M30 or M65 was found in the sera of patients with HCC after sorafenib., Conclusion: The findings indicate that sorafenib is not a potent inducer of HCC cell death in most patients., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)
- Published
- 2015
20. The retinoblastoma (Rb) protein regulates ferroptosis induced by sorafenib in human hepatocellular carcinoma cells.
- Author
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Louandre C, Marcq I, Bouhlal H, Lachaier E, Godin C, Saidak Z, François C, Chatelain D, Debuysscher V, Barbare JC, Chauffert B, and Galmiche A
- Subjects
- Animals, Blotting, Western, Carcinoma, Hepatocellular metabolism, Cell Proliferation drug effects, Female, Humans, Liver Neoplasms drug therapy, Liver Neoplasms metabolism, Liver Neoplasms pathology, Mice, Mice, Inbred BALB C, Mice, Nude, Mitochondria drug effects, Mitochondria metabolism, Mitochondria pathology, Niacinamide pharmacology, Reactive Oxygen Species metabolism, Sorafenib, Tumor Cells, Cultured, Xenograft Model Antitumor Assays, Antineoplastic Agents pharmacology, Apoptosis drug effects, Carcinoma, Hepatocellular drug therapy, Carcinoma, Hepatocellular pathology, Necrosis, Niacinamide analogs & derivatives, Oxidative Stress drug effects, Phenylurea Compounds pharmacology, Retinoblastoma Protein metabolism
- Abstract
Sorafenib is the treatment of reference for advanced hepatocellular carcinoma (HCC), the most frequent form of primary liver tumour. The loss of function of the retinoblastoma (Rb) protein is an important event during liver carcinogenesis, but it is unclear whether the Rb status modulates the response of HCC cells to sorafenib. Here, we examined this question in HCC cells with reduced levels of Rb achieved through stable RNA interference. We show that HCC cells with reduced levels of Rb exhibit a two- to threefold increase in cell death induction upon exposure to sorafenib compared with controls. Sorafenib treatment of Balb/c nude mice that received tumour xenografts derived from HCC cells with reduced Rb levels resulted in complete tumour regression in 50% of the animals treated, compared with tumour stabilization in mice that received control cells. We show that, upon exposure to sorafenib, the Rb-negative status of HCC cells promotes the occurrence of ferroptosis, a form of oxidative necrosis. The findings highlight the role of Rb in the response of HCC cells to sorafenib and the regulation of ferroptosis., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2015
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21. Optimal cut points for quality of life questionnaire-core 30 (QLQ-C30) scales: utility for clinical trials and updates of prognostic systems in advanced hepatocellular carcinoma.
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Diouf M, Bonnetain F, Barbare JC, Bouché O, Dahan L, Paoletti X, and Filleron T
- Subjects
- Carcinoma, Hepatocellular pathology, Clinical Trials as Topic, France, Humans, Liver Neoplasms pathology, Surveys and Questionnaires, Carcinoma, Hepatocellular epidemiology, Liver Neoplasms epidemiology, Prognosis, Quality of Life
- Abstract
Background: Health-related quality of life (QoL) has been validated as a prognostic factor for cancer patients; however, to be used in routine practice, QoL scores must be dichotomized. Cutoff points are usually based on arbitrary percentile values. We aimed to identify optimal cutoff points for six QoL scales and to quantify their added utility in the performance of four prognostic classifications in patients with hepatocellular carcinoma (HCC)., Methods: We reanalyzed data of 271 patients with advanced HCC recruited between July 2002 and October 2003 from 79 institutions in France in the CHOC trial, designed to assess the efficacy of long-acting octreotide. QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (QLQ-C30). The scores ranged from 0 to 100. Identification of optimal cutoff points was based on the method of Faraggi and Simon [Stat Med 1996;15:2203-2213]. Improvement in the performance of prognostic classifications was studied with Harrell's C-index, the net reclassification improvement (NRI), and integrated discrimination improvement (IDI)., Results: We found that optimal cutoff points were 50 for global health, 58.33 for physical functioning, 66.67 for role functioning, 66.67 for fatigue, 0 for dyspnea, and 33.33 for diarrhea. The addition of QoL and clinical factors improved the performance of all four prognostic classifications, with improvement in the range of 0.02-0.09 for the C-index, 0.24-0.78 for 3-month NRI, and 0.02-0.10 for IDI., Conclusion: These cutoff values for QoL scales can be useful to identify HCC patients with very poor prognosis and thus improve design of clinical trials and treatment adjustment for these patients., (©AlphaMed Press.)
- Published
- 2015
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22. [Should cases of hepatocellular carcinoma be discussed by non-specialized multidisciplinary team meetings?].
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Barbare JC, Franco D, André T, Bronowicki JP, Merle P, Péron JM, Raoul JL, Seitz JF, and Ychou M
- Subjects
- France, Health Care Surveys, Humans, Patient Care Planning statistics & numerical data, Carcinoma, Hepatocellular therapy, Interdisciplinary Communication, Liver Neoplasms therapy, Patient Care Team statistics & numerical data, Specialization
- Abstract
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.
- Published
- 2014
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23. New biological perspectives for the improvement of the efficacy of sorafenib in hepatocellular carcinoma.
- Author
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Galmiche A, Chauffert B, and Barbare JC
- Subjects
- Antineoplastic Agents administration & dosage, Biomarkers, Tumor metabolism, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Clinical Trials as Topic, Humans, Liver Neoplasms metabolism, Liver Neoplasms pathology, Niacinamide administration & dosage, Precision Medicine methods, Protein Kinase Inhibitors administration & dosage, Sorafenib, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Niacinamide analogs & derivatives, Phenylurea Compounds administration & dosage
- Abstract
Sorafenib, an orally-available kinase inhibitor, is the only medical treatment with a proven efficacy against Hepatocellular Carcinoma (HCC). Although the overall clinical efficacy of sorafenib is modest, recent experimental results have uncovered new potential strategies that may increase its clinical benefits. The potential implication of Receptor Tyrosine Kinases (RTKs), such as the Epidermal Growth Factor Receptor (EGFR), in the development of resistance to sorafenib highlights the importance of the RAF kinase pathway. Various strategies aiming to optimize the control exerted over this pathway by combining sorafenib with other targeted molecules (such as anti-EGFR, anti-MEK) are under investigation. Increasing the cytotoxicity of sorafenib in HCC, either through apoptosis or through new forms of non-apoptotic cell death, such as ferroptosis, may also promote more sustained tumour regression. Finally, the heterogeneity of individual responses to sorafenib is increasingly recognised, even though clinically-applicable biomarkers remain to be identified. Here, we discuss how molecular genetics and complementary approaches such as short term culture of tumour samples could help to personalize the use of sorafenib., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2014
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24. Iron-dependent cell death of hepatocellular carcinoma cells exposed to sorafenib.
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Louandre C, Ezzoukhry Z, Godin C, Barbare JC, Mazière JC, Chauffert B, and Galmiche A
- Subjects
- Antineoplastic Agents therapeutic use, Cell Death drug effects, Cell Line, Tumor, Cell Survival, Cyclohexylamines pharmacology, Deferoxamine chemistry, Extracellular Signal-Regulated MAP Kinases metabolism, Humans, Iron chemistry, Iron Regulatory Protein 2 genetics, Liver Neoplasms pathology, MAP Kinase Kinase Kinases metabolism, MAP Kinase Signaling System, Niacinamide pharmacology, Niacinamide therapeutic use, Oxidative Stress, Phenylenediamines pharmacology, Phenylurea Compounds therapeutic use, Protein Kinase Inhibitors pharmacology, Protein Kinase Inhibitors therapeutic use, RNA Interference, Siderophores chemistry, Sorafenib, raf Kinases metabolism, Antineoplastic Agents pharmacology, Carcinoma, Hepatocellular drug therapy, Deferoxamine pharmacology, Iron metabolism, Liver Neoplasms drug therapy, Niacinamide analogs & derivatives, Phenylurea Compounds pharmacology
- Abstract
The multikinase inhibitor sorafenib is currently the treatment of reference for advanced hepatocellular carcinoma (HCC). In our report, we examined the cytotoxic effects of sorafenib on HCC cells. We report that the depletion of the intracellular iron stores achieved by using the iron chelator deferoxamine (DFX) strikingly protects HCC cells from the cytotoxic effects of sorafenib. The protective effect of the depletion of intracellular iron stores could not be explained by an interference with conventional forms of programmed cell death, such as apoptosis or autophagic cell death. We also found that DFX did not prevent sorafenib from reaching its intracellular target kinases. Instead, the depletion of intracellular iron stores prevented sorafenib from inducing oxidative stress in HCC cells. We examined the possibility that sorafenib might exert a cytotoxic effect that resembles ferroptosis, a form of cell death in which iron-dependent oxidative mechanisms play a pivotal role. In agreement with this possibility, we found that pharmacological inhibitors (ferrostatin-1) and genetic procedures (RNA interference against IREB-2) previously reported to modulate ferroptosis, readily block the cytotoxic effects of sorafenib in HCC cells. Collectively, our findings identify ferroptosis as an effective mechanism for the induction of cell death in HCC. Ferroptosis could potentially become a goal for the medical treatment of HCC, thus opening new avenues for the optimization of the use of sorafenib in these tumors., (© 2013 UICC.)
- Published
- 2013
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25. Heterogeneous sensitivity of hepatocellular carcinoma to sorafenib revealed by the short-term culture of tumor fragments.
- Author
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Godin C, Dupont S, Ezzoukhry Z, Louandre C, Chatelain D, Henaut L, Sabbagh C, Regimbeau JM, Maziere JC, Barbare JC, Chauffert B, and Galmiche A
- Subjects
- Aged, Aged, 80 and over, Animals, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Female, Humans, Immunoblotting, Liver Neoplasms metabolism, Liver Neoplasms pathology, Male, Mice, Mice, Inbred BALB C, Mice, Nude, Middle Aged, Mitogen-Activated Protein Kinase 1 metabolism, Mitogen-Activated Protein Kinase 3 metabolism, Niacinamide pharmacology, Phosphorylation drug effects, Sorafenib, Tumor Cells, Cultured, Antineoplastic Agents pharmacology, Carcinoma, Hepatocellular drug therapy, Drug Resistance, Neoplasm, Liver Neoplasms drug therapy, Niacinamide analogs & derivatives, Phenylurea Compounds pharmacology
- Abstract
Background/aim: Sorafenib is currently the only medical treatment with proven efficacy against hepatocellular carcinoma (HCC). HCC cell lines display heterogeneous sensitivity to sorafenib, but little is known about the sensitivity of clinical tumors. We aimed to examine this aspect., Materials and Methods: Using experimental tumors generated in nude mice, we set up a technique for short-term culture of HCC fragments. We applied this technique to six human HCC samples obtained from surgical resection., Results: HCC fragments in culture retain their morphology and viability for at least 48 h, permitting an in vitro analysis of the effect of sorafenib on the Extracellular signal-regulated kinase (ERK) cascade. HCC exhibit heterogeneous individual responses, ranging from potent inhibition to paradoxical activation of this oncogenic cascade., Conclusion: Our observations highlight the heterogeneous sensitivity of HCC to sorafenib, and point to the potential interest of short-term culture of tumor fragments for personalizing the medical treatment of HCC.
- Published
- 2013
26. The added value of quality of life (QoL) for prognosis of overall survival in patients with palliative hepatocellular carcinoma.
- Author
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Diouf M, Filleron T, Barbare JC, Fin L, Picard C, Bouché O, Dahan L, Paoletti X, and Bonnetain F
- Subjects
- Adult, Aged, Female, Humans, Male, Middle Aged, Prognosis, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular psychology, Liver Neoplasms mortality, Liver Neoplasms psychology, Quality of Life
- Abstract
Background & Aims: Several prognostic classifications (PCs) have been developed for use in palliative care in patients with hepatocellular carcinoma (HCC). We have recently suggested that CLIP combined with WHO PS has the greatest discriminative power. We evaluated the prognostic value of quality of life (QoL) data and whether the latter could improve classification of palliative HCC patients., Methods: This was a reanalysis from the CHOC trial with an evaluation of the discriminative power for overall survival (OS) of the established CLIP/GRETCH/BCLC/BoBar prognostic systems alone and then in association with each of the following groups of parameters: selected clinical factors, QoL as continuous variables, dichotomized QoL, selected clinical factors and continuous QoL, selected clinical factors and dichotomized QoL. Baseline QoL was assessed using the EORTC QLQ-C30. Discriminative power was evaluated with the Harrell's C-index and net reclassification improvement., Results: Quality of life was available in 79% of the patients (n=271). Univariate analysis revealed that better role functioning (HR=0.991 [0.987-0.995]) and better physical functioning (0.991 [0.984-0.997]) scores were associated with longer survival. In contrast, poorer score for fatigue (1.011 [1.006-1.015]) and diarrhoea (1.008 [1.002-1.013]) were associated with shorter survival. After adjustment for clinical and sociodemographic variables, only better role functioning score (0.993 [0.988-0.998]) was associated with longer survival. Adding oedema, hepatomegaly, fatigue and diarrhoea QoL scales to CLIP resulted in the best performance., Conclusions: Our results confirm that QoL scales are independent prognostic factors of OS in palliative HCC patients. Incorporation of QoL data improved all the studied PCs., (Copyright © 2012 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Published
- 2013
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27. [Why no consensus prognostic classification for hepatocellular carcinoma?].
- Author
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Barbare JC, Bellenguez A, and Diouf M
- Subjects
- Carcinoma, Hepatocellular pathology, Humans, Liver Neoplasms pathology, Neoplasm Staging methods, Professional Practice statistics & numerical data, Prognosis, Severity of Illness Index, Carcinoma, Hepatocellular classification, Carcinoma, Hepatocellular diagnosis, Consensus, Liver Neoplasms classification, Liver Neoplasms diagnosis
- Published
- 2013
28. EGFR activation is a potential determinant of primary resistance of hepatocellular carcinoma cells to sorafenib.
- Author
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Ezzoukhry Z, Louandre C, Trécherel E, Godin C, Chauffert B, Dupont S, Diouf M, Barbare JC, Mazière JC, and Galmiche A
- Subjects
- Cell Line, Tumor, Drug Resistance, Neoplasm, Humans, Niacinamide analogs & derivatives, Phenylurea Compounds, RNA Interference, Sorafenib, Antineoplastic Agents therapeutic use, Benzenesulfonates therapeutic use, Carcinoma, Hepatocellular drug therapy, ErbB Receptors metabolism, Liver Neoplasms drug therapy, Pyridines therapeutic use
- Abstract
Sorafenib is currently the medical treatment of reference for hepatocellular carcinoma (HCC), but it is not known whether sorafenib is equally active in all HCC. Here, our aim was to explore intrinsic differences in the response of HCC cells to sorafenib, to identify potential mechanisms leading to primary resistance to this treatment. We analyzed a panel of six human HCC cell lines and compared the activity of the main oncogenic kinase cascades, their clonogenic potential, proliferation and apoptosis upon exposure to sorafenib. We report that HCC cells present important differences in their response to sorafenib, and that some cell lines are more resistant to the actions of sorafenib than others. We identify the activated epidermal growth factor receptor (EGFR) as a parameter that promotes the resistance of HCC cells to sorafenib. In resistant cells, the efficacy of sorafenib was increased when EGFR was inhibited, as was demonstrated using two chemical inhibitors (erlotinib or gefitinib), a monoclonal antibody directed against EGFR (cetuximab), and RNA interference directed against EGFR. A combination of EGFR inhibitors and sorafenib affords a better control over HCC proliferation, most likely through an improved blockade of the RAF kinases. Our findings therefore confirm the importance of RAF kinases as therapeutic targets in HCC, and identify EGFR as a determinant of the sensitivity of HCC cells to sorafenib. Our findings bear possible implications for the improvement of the efficacy of sorafenib in HCC, and might be useful for the identification of predictive biomarkers in this context., (Copyright © 2012 UICC.)
- Published
- 2012
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29. Development and validation of a new prognostic score of death for patients with hepatocellular carcinoma in palliative setting.
- Author
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Tournoux-Facon C, Paoletti X, Barbare JC, Bouché O, Rougier P, Dahan L, Lombard-Bohas C, Faroux R, Raoul JL, Bedenne L, and Bonnetain F
- Subjects
- Aged, Alkaline Phosphatase blood, Carcinoma, Hepatocellular pathology, Female, France epidemiology, Humans, Kaplan-Meier Estimate, Liver Neoplasms pathology, Male, Middle Aged, Neoplasm Staging, Predictive Value of Tests, Prognosis, Proportional Hazards Models, alpha-Fetoproteins metabolism, Carcinoma, Hepatocellular mortality, Carcinoma, Hepatocellular therapy, Liver Neoplasms mortality, Liver Neoplasms therapy, Palliative Care
- Abstract
Background & Aims: Patients with hepatocellular carcinoma (HCC) in a palliative setting have a poor prognosis despite recent therapeutic progress. Several prognostic scores, such as the BCLC and the CLIP, have been shown to be useful in helping select treatment options ranging from transplantation to palliative care. However, the discriminatory ability of these scores is inadequate in palliative settings, which concern about 70% of HCC patients. In this paper, we propose and validate a new prognostic score for patients in the palliative setting., Methods: The prognostic score was developed on a set of 416 patients from a negative randomized clinical trial conducted by the Fédération Francophone de Cancers Digestifs. It was then subsequently validated on a second set of 271 patients from another negative trial. Backward selection was used to identify independent baseline characteristics. Measures of discrimination and predictive values were computed to assess the quality of the developed score. Comparisons with the BCLC and the CLIP - with and without the WHO performance status (PS) score - were performed., Results: Tumour morphology, portal vein obstruction, metastasis, ascites, jaundice, alpha-foetoprotein, and serum alkaline phosphatase were included in the final score. From the training dataset, three groups of increasing risk were defined, and these were associated with hazard ratios (HR) of 2.13 and HR = 5.72. Similar results were obtained on the validation dataset. This score provides a better discriminatory ability than BCLC and CLIP in this setting. Unfortunately, absolute performances for these scores remain poor., Conclusions: The new prognostic score and CLIP + PS are recommended in palliative settings. However, new prognostic variables are necessary., (Copyright © 2010 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.)
- Published
- 2011
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30. BAD, a proapoptotic member of the BCL2 family, is a potential therapeutic target in hepatocellular carcinoma.
- Author
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Galmiche A, Ezzoukhry Z, François C, Louandre C, Sabbagh C, Nguyen-Khac E, Descamps V, Trouillet N, Godin C, Regimbeau JM, Joly JP, Barbare JC, Duverlie G, Mazière JC, and Chatelain D
- Subjects
- Antineoplastic Agents pharmacology, Benzenesulfonates pharmacology, Biomarkers, Tumor metabolism, Biphenyl Compounds pharmacology, Blotting, Western, Carcinoma, Hepatocellular drug therapy, Cell Line, Tumor, Cell Proliferation drug effects, Drug Synergism, Humans, Liver drug effects, Liver metabolism, Liver pathology, Liver Neoplasms drug therapy, Niacinamide analogs & derivatives, Nitrophenols pharmacology, Phenylurea Compounds, Piperazines pharmacology, Pyridines pharmacology, RNA, Messenger genetics, Reverse Transcriptase Polymerase Chain Reaction, Sorafenib, Sulfonamides pharmacology, Apoptosis drug effects, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, Liver Neoplasms metabolism, Liver Neoplasms pathology, Proto-Oncogene Proteins c-bcl-2 metabolism
- Abstract
Proteins of the BCL2 family are key regulators of apoptosis. Their expression levels are frequently altered in cancers, enabling tumor cells to survive. To gain insight into the pathogenesis of hepatocellular carcinoma (HCC), we performed a comprehensive survey of the expression of the members of the BCL2 family in samples obtained from surgically resected HCCs. Here, we report the occurrence of a new molecular anomaly, consisting of a strong reduction in the expression of the proapoptotic protein BAD in HCC compared with surrounding nontumoral tissue. We investigate the function of BAD in a panel of HCC cell lines. Using gene overexpression and RNA interference, we show that BAD is involved in the cytotoxic effects of sorafenib, a multikinase blocker, which is currently the sole therapeutic drug effective for the treatment of HCC. Finally, we report that ABT-737, a compound that interacts with proteins of the BCL2 family and exhibits a BAD-like reactivity, sensitizes HCC cells toward sorafenib-induced apoptosis. Collectively, our findings indicate that BAD is a key regulator of apoptosis in HCC and an important determinant of HCC cell response to sorafenib.
- Published
- 2010
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31. Hepatocellular carcinoma--what's new?
- Author
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Vullierme MP, Paradis V, Chirica M, Castaing D, Belghiti J, Soubrane O, Barbare JC, and Farges O
- Subjects
- Antineoplastic Agents therapeutic use, Benzenesulfonates therapeutic use, Carcinoma, Hepatocellular etiology, Hepatectomy, Humans, Liver Neoplasms etiology, Liver Transplantation, Metabolic Syndrome complications, Niacinamide analogs & derivatives, Phenylurea Compounds, Prognosis, Pyridines therapeutic use, Risk Factors, Sorafenib, Treatment Outcome, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular therapy, Liver Neoplasms diagnosis, Liver Neoplasms therapy
- Abstract
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., ((c) 2010. Published by Elsevier Masson SAS.)
- Published
- 2010
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32. Somatostatin receptor scintigraphy screening in advanced hepatocarcinoma: A multi-center French study.
- Author
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Nguyen-Khac E, Ollivier I, Aparicio T, Moullart V, Hugentobler A, Lebtahi R, Lobry C, Susini C, Duhamel C, Hommel S, Cadranel JF, Joly JP, Barbare JC, Tramier B, and Dupas JL
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular metabolism, Carcinoma, Hepatocellular pathology, France, Humans, Immunohistochemistry, Indium Radioisotopes pharmacokinetics, Liver Neoplasms metabolism, Liver Neoplasms pathology, Male, Middle Aged, Multivariate Analysis, Neoplasm Staging, Radionuclide Imaging methods, Radiopharmaceuticals pharmacokinetics, Receptors, Somatostatin metabolism, Somatostatin analogs & derivatives, Somatostatin pharmacokinetics, Treatment Outcome, Carcinoma, Hepatocellular diagnostic imaging, Liver Neoplasms diagnostic imaging, Receptors, Somatostatin analysis
- Abstract
Background: Somatostatin receptor scintigraphy (SRS) has been reported for receptor (SSTR) screening in advanced hepatocarcinoma (aHC) prior to somatostatin analogue treatment., Aims: To evaluate SSTR screening with SRS in aHC patients., Results: Seventy aHC patients (63 men) aged 65 +/- 11 y were included, with alcohol, viral or other causes cirrhosis in 35 (50%), 23 (33%), 12 (17%) cases respectively. CLIP score was 2.7 +/- 1.7, with more than three nodules in 37 (53%) cases. Largest nodule measured 7.6 +/- 4.5 cm. Median alpha-fetoprotein was 574 UI/mL. SRS was positive in 25/70 (35.7%) livers and 7/17 (41.2%) metastatic sites. Positive SRS patients differed from others for tumor size (9.2 +/- 4 vs. 6.7 +/- 4.6 cm, p = 0.03), prothrombin time (PT) (75.2 +/- 15.2 vs. 61.9 +/- 19%, p = 0.005), albumin (34.1 +/- 5.9 vs. 30.5 +/- 7.2 g/L, p = 0.04) and Child-Pugh (6.7 +/- 1.8 vs. 7.7 +/- 2.3, p = 0.04). After multivariate analysis, only PT was associated with positive SRS (p = 0.028). Immunohistochemistry was positive for SSTR2s in 6/7 tumors (SRS uptake in 5/6 cases)., Methods: SRS was performed prior treatment, with images at 4, 24 and 48 h. For seven tumors, SSTR2 subtype was detected immunohistochemically., Conclusions: In advanced hepatocarcinoma, we report SRS uptake in 35.7% of livers and 41.2% of metastatic sites. SRS value in screening patients for somatostatin analogue treatment remains to be assessed.
- Published
- 2009
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33. Marked iron overload related to ribavirin and iron sulfate treatment in a patient with active viral C cirrhosis.
- Author
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Jouannaud V, Cadranel JF, Dumouchel P, Cazier A, Capron D, Rochette J, and Barbare JC
- Subjects
- Drug Therapy, Combination, Female, Ferritins blood, Hepatitis C, Chronic blood, Humans, Middle Aged, Antiviral Agents adverse effects, Ferrous Compounds adverse effects, Hepatitis C, Chronic drug therapy, Iron Overload chemically induced, Ribavirin adverse effects
- Abstract
Increased ferritin levels are common in the course of chronic hepatitis C, regardless of antiviral therapy. Usually, this increase in ferritin levels has minimal clinical and biological impact, and drops after therapy discontinuation. We report here on a dramatic increase in ferritin levels in a cirrhotic patient with hepatitis C treated by ribavirin monotherapy and oral iron sulphate, and discuss the possible mechanisms of this deleterious effect.
- Published
- 2009
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34. Treatment of advanced hepatocellular carcinoma with long-acting octreotide: a phase III multicentre, randomised, double blind placebo-controlled study.
- Author
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Barbare JC, Bouché O, Bonnetain F, Dahan L, Lombard-Bohas C, Faroux R, Raoul JL, Cattan S, Lemoine A, Blanc JF, Bronowicki JP, Zarski JP, Cazorla S, Gargot D, Thevenot T, Diaz E, Bastie A, Aparicio T, and Bedenne L
- Subjects
- Adult, Aged, Aged, 80 and over, Antineoplastic Agents, Hormonal adverse effects, Double-Blind Method, Drug Administration Schedule, Female, Humans, Male, Middle Aged, Octreotide adverse effects, Quality of Life, Survival Analysis, Treatment Outcome, Antineoplastic Agents, Hormonal therapeutic use, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Octreotide therapeutic use
- Abstract
Background: A previous study reported a significant survival benefit for octreotide compared with no treatment in patients with advanced hepatocellular carcinoma (HCC). This was investigated further in this multicentre study., Patients and Methods: Two hundred and seventy two patients with HCC who were ineligible for curative treatments or had relapsed following potentially curative therapies were randomised to receive long-acting octreotide, 30 mg as an intramuscular injection once every 4 weeks for up to 2 years, or placebo., Results: At the time of the final analysis, median overall survival (OS) was 6.53 months (95% confidence interval [CI], 4.8-8.3) for octreotide versus 7.03 months (95% CI, 5.43-8.53) for placebo (p=0.34). Progression-free survival (p=0.26) also did not differ significantly between the two treatment groups. No objective responses were achieved in the octreotide group but 33% of patients achieved disease stabilisation for a mean time of 5.5 months (95% CI, 1.1-9.9). The median time until definitive global health score deterioration (according to QLQ-C30) was 2.3 months (95% CI, 1.4-3.7) in the octreotide and 4 months (95% CI, 2.2-5.7) in the placebo group (p=0.09). There were four objective responses in the placebo group. Octreotide was well tolerated; seven patients reported severe adverse events possibly related to octreotide and there were no cases of haematoma or cholecystitis., Conclusions: In patients with advanced HCC, octreotide has a favourable safety profile but does not improve OS and could have a negative impact on quality of life.
- Published
- 2009
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35. [Management of hepatocellular carcinoma. Where are we now? What's next?].
- Author
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Taieb J, Barbare JC, Boussaha T, Cunha AS, Baere Td, Rosmorduc O, Zucman-Rossi J, and Franco D
- Subjects
- Antineoplastic Agents therapeutic use, Carcinoma, Hepatocellular surgery, ErbB Receptors antagonists & inhibitors, Humans, Liver Cirrhosis complications, Liver Neoplasms surgery, Neoadjuvant Therapy methods, Vascular Endothelial Growth Factor A antagonists & inhibitors, Carcinoma, Hepatocellular therapy, Catheter Ablation methods, Chemoembolization, Therapeutic methods, Liver Neoplasms therapy, Liver Transplantation
- Abstract
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.
- Published
- 2009
- Full Text
- View/download PDF
36. [How to improve patients and investigators' information on clinical trials: the example of French registry for clinical trials in oncology].
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Pauporté I, Manach E, Bachouche N, Hommais A, Détry S, Legrand-Lane C, and Barbare JC
- Subjects
- Biomedical Research, France, Humans, Internet, Clinical Trials as Topic, Neoplasms therapy, Patient Education as Topic, Registries, Research Personnel
- Abstract
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.
- Published
- 2008
- Full Text
- View/download PDF
37. Prevalence of hepatitis C infection and risk factors in hospitalized diabetic patients: results of a cross-sectional study.
- Author
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Cadranel JF, Di Martino V, Lambrey G, Mourlhon C, Nalet B, Anciaux ML, Richard C, Bigué JP, Barjon JN, Bories C, Barbare JC, Halimi C, Ribière O, Eugène C, Pauwels A, Jeanne S, Donato L, Dumouchel P, Pariente A, Duverlie G, Devergie B, Arlot S, and Capron D
- Subjects
- Adult, Aged, Cross Infection epidemiology, Cross Infection transmission, Epidemiologic Methods, Female, France epidemiology, Hepatitis B transmission, Hepatitis C Antibodies blood, Hospitalization statistics & numerical data, Humans, Male, Middle Aged, Substance Abuse, Intravenous complications, Substance Abuse, Intravenous epidemiology, Transfusion Reaction, Diabetes Mellitus epidemiology, Hepatitis B epidemiology
- Abstract
Objectives: Although there may exist a nosocomial risk of hepatitis C virus (HCV) infection in patients with type 1 or type 2 diabetes, this risk has not been fully investigated thus far and its magnitude is unknown. The aim of this multicenter cross-sectional study was to evaluate the prevalence of, and risk factors for, hepatitis C infection in consecutive hospitalized patients with diabetes and to assess the nosocomial risk and magnitude of HCV infection in these patients., Patients and Methods: Consecutive hospitalized patients with diabetes seen in 11 French hepatogastroenterology and diabetology departments were studied. The prevalence of anti-HCV antibodies was compared with that observed in healthy blood donors and individuals seen during routine medical checkup. Diabetic patients with anti-HCV antibodies were compared with patients without anti-HCV antibodies for assessment of risk factors., Results: In total 1561 patients were studied. Independent risk factors for HCV infection were assessed through multivariate analysis. Thirty-three patients (2.11%) had anti-HCV antibodies and 21 (63.70%) had HCV identified risk factors. The prevalence of HCV infection was higher in patients with diabetes than in blood donors (0.08%) or healthy controls (0.20%) (P<0.001). Multivariate analysis identified four independent risk factors for HCV infection: blood transfusion before 1991 [odds ratio (OR)=2.88, P=0.033], intravenous drug use (OR=21.37, P=0.012), treatment in a hepatogastroenterology center (OR=4.17, P=0.002) and a high number (>2) of previous admissions since the onset of diabetes (OR=2.52, P=0.039)., Conclusion: A nosocomial source of HCV infection in hospitalized diabetic patients is suggested by the increased risk of HCV infection associated with the number of hospitalizations. This may account for at least 36% of cases of HCV infection.
- Published
- 2008
- Full Text
- View/download PDF
38. Quality of life as a prognostic factor of overall survival in patients with advanced hepatocellular carcinoma: results from two French clinical trials.
- Author
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Bonnetain F, Paoletti X, Collette S, Doffoel M, Bouché O, Raoul JL, Rougier P, Masskouri F, Barbare JC, and Bedenne L
- Subjects
- Aged, Carcinoma, Hepatocellular mortality, Clinical Trials as Topic, Female, France, Health Status Indicators, Humans, Male, Middle Aged, Pilot Projects, Prognosis, Psychological Tests, Psychometrics, Surveys and Questionnaires, Carcinoma, Hepatocellular psychology, Quality of Life
- Abstract
Aim: The aims of our study were to assess quality of life (QoL) as a prognostic factor of overall survival (OS) and to determine whether QoL data improved three prognostic classifications among French patients with advanced hepatocellular carcinoma (HCC)., Methods: We pooled two randomized clinical trials conducted by the Fédération Francophone de Cancérologie Digestive in a palliative setting. In each trial QoL was assessed at baseline using the Spitzer QoL Index (0-10). Three prognostic classifications were calculated: Okuda, Cancer of the Liver Italian Program (CLIP), and Barcelona Clinic Liver Cancer group (BCLC) scores. To explore whether the scores could be improved by including QoL, univariate Cox analyses of all potential baseline predictors were performed. A final multivariate Cox model was constructed including only significant multivariate baseline variables likely to result in improvement of each scoring system. In order to retain the best prognostic variable to add for each score, we compared Akaike information criterion, likelihood ratio, and Harrell's C-index. Cox analyses were stratified for each trial., Results: Among 538 included patients, QoL at baseline was available for 489 patients (90%). Longer median OS was significantly associated with higher Spitzer scores at baseline, ranging from 2.17 months (Spitzer=3) to 8.93 months (Spitzer=10). Variables retained in the multivariate Cox model were: jaundice, hepatomegaly, hepatalgia, portal thrombosis, alphafetoprotein, bilirubin, albumin, small HCC, and Spitzer QoL Index (hazard ratio=0.84 95% CI [0.79-0.90]). According to Harrell's C-index, QoL was the best prognostic variable to add. CLIP plus the Spitzer QoL Index had the most discriminating value (C=0.71)., Conclusions: Our results suggest that QoL is an independent prognostic factor for survival in HCC patients with mainly alcoholic cirrhosis. The prognostic value of CLIP score could be improved by adding Spitzer QOL Index scores.
- Published
- 2008
- Full Text
- View/download PDF
39. Prognosis of advanced hepatocellular carcinoma: comparison of three staging systems in two French clinical trials.
- Author
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Collette S, Bonnetain F, Paoletti X, Doffoel M, Bouché O, Raoul JL, Rougier P, Masskouri F, Bedenne L, and Barbare JC
- Subjects
- Adult, Aged, Aged, 80 and over, Carcinoma, Hepatocellular etiology, Carcinoma, Hepatocellular mortality, Female, France, Humans, Liver Cirrhosis, Alcoholic complications, Liver Neoplasms etiology, Liver Neoplasms mortality, Male, Middle Aged, Neoplasm Staging mortality, Palliative Care, Prognosis, Survival Analysis, Carcinoma, Hepatocellular pathology, Liver Neoplasms pathology, Neoplasm Staging methods
- Abstract
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.
- Published
- 2008
- Full Text
- View/download PDF
40. [Biermer's anemia and microcytic anemia].
- Author
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Saint-Leger P, Barbare JC, and Dupas JL
- Subjects
- Adult, Female, Humans, Anemia, Iron-Deficiency diagnosis
- Published
- 2008
- Full Text
- View/download PDF
41. [Use of sorafenib (Nexavar) in the treatment of hepatocellular carcinoma: PRODIGE AFEF recommendations].
- Author
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Boige V, Barbare JC, and Rosmorduc O
- Subjects
- Antineoplastic Agents adverse effects, Benzenesulfonates adverse effects, Clinical Protocols, Contraindications, Disease-Free Survival, Humans, Neoadjuvant Therapy, Niacinamide analogs & derivatives, Palliative Care, Phenylurea Compounds, Protein Kinase Inhibitors adverse effects, Pyridines adverse effects, Randomized Controlled Trials as Topic, Remission Induction, Sorafenib, Survival Rate, Antineoplastic Agents therapeutic use, Benzenesulfonates therapeutic use, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Protein Kinase Inhibitors therapeutic use, Pyridines therapeutic use, Receptors, Vascular Endothelial Growth Factor antagonists & inhibitors, raf Kinases antagonists & inhibitors
- Published
- 2008
- Full Text
- View/download PDF
42. Treatment outcomes for hepatocellular carcinoma using chemoembolization in combination with other therapies.
- Author
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Tournoux C, Paoletti X, and Barbare JC
- Subjects
- Humans, Meta-Analysis as Topic, Randomized Controlled Trials as Topic, Carcinoma, Hepatocellular therapy, Chemoembolization, Therapeutic, Liver Neoplasms therapy
- Published
- 2007
- Full Text
- View/download PDF
43. Management practices for gastrointestinal hemorrhage related to portal hypertension in cirrhotic patients: evaluation of the impact of the Paris consensus workshop.
- Author
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Charpignon C, Oberti F, Bernard P, Bartoli ER, Pauwels A, Renard P, Cadranel JF, Bernard-Chabert B, Barbare JC, Ingrand I, Ingrand P, and Beauchant M
- Subjects
- Adrenergic beta-Antagonists therapeutic use, Antibiotic Prophylaxis statistics & numerical data, Drug Utilization statistics & numerical data, France, Gastrointestinal Hemorrhage etiology, Guideline Adherence, Humans, Practice Guidelines as Topic, Propranolol therapeutic use, Prospective Studies, Severity of Illness Index, Surveys and Questionnaires, Vasoconstrictor Agents therapeutic use, Gastrointestinal Hemorrhage therapy, Hypertension, Portal complications, Liver Cirrhosis complications, Practice Patterns, Physicians' statistics & numerical data
- Abstract
Objectives: The purpose of this before-after observational survey was to evaluate compliance with good clinical practice guidelines for gastrointestinal hemorrhage related to portal hypertension and the impact of the French Consensus Workshop held in Paris in 2003., Methods: Data were recorded concerning episodes of gastrointestinal hemorrhage occurring in cirrhotic patients using a survey questionnaire in 2003 before the workshop and again in 2004., Results: Seventy-six index episodes were included in 2003 and 84 in 2004 in patients attending French hospitals. Before hospital admission, primary prophylaxis was similar in 2003 and 2004, but beta blockers were used alone more often in 2004 for secondary prophylaxis (42% vs 19%, P=0.018). The time from onset of bleeding to hospital admission was greater than 12 hours for 43 and 42% of patients and was not shorter in the event of recurrent hemorrhage. At admission, vasoactive drugs were given earlier in 2004 (<2h: 68% vs 35%, P<0.001). Use of antibiotic prophylaxis was similar in 2003 and 2004 (70% vs 61%, P=0.098), and was more common for Child-Pugh B or C patients (P=0.044)., Conclusion: The Paris Consensus Workshop enabled improved clinical practices. Weak points were insufficient screening for cirrhosis, long delay before admission, insufficient use of antibiotic prophylaxis which should be systematic.
- Published
- 2007
- Full Text
- View/download PDF
44. Hepatocellular carcinoma (HCC): an update.
- Author
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Rougier P, Mitry E, Barbare JC, and Taieb J
- Subjects
- Chemoembolization, Therapeutic, Chemotherapy, Adjuvant, Decision Making, Hepatectomy, Humans, Immunotherapy, Adoptive, Liver Cirrhosis complications, Liver Transplantation, Palliative Care, Radiotherapy, Adjuvant, Randomized Controlled Trials as Topic, Carcinoma, Hepatocellular therapy, Liver Neoplasms therapy
- Abstract
In the absence of large randomized trials, the current treatment strategy for hepatocellular carcinoma (HCC) remains a matter of choice depending mostly on retrospective studies, experience of centers, and the technical therapeutic possibilities. In fact, treatment decisions must be based on HCC extension and liver function, which is dependent on underlying liver disease. Cirrhosis limits therapeutic choices, life expectancy, and tolerance to therapy. Surgical resection and/or local destruction are the most common curative treatments. Orthotopic liver transplantation is probably the best treatment for small HCC developed in cirrhosis because it treats tumor, cirrhosis, and preneoplastic lesions at the same time. However, this treatment method is feasible in fewer than 5% of cases. Adjuvant treatments include transarterial chemoembolization, chemotherapy, polyprenoic acid, interferon, adoptive immunotherapy, and intra-arterial radioactive lipiodol. Results from trials warrant confirmation in larger randomized trials to show a clear survival benefit on recurrence rate, secondary prevention, and overall survival. Chemoembolization is the only palliative treatment that has been proven to be active, unlike systemic chemotherapy, immunotherapy, and hormone therapy, whose activity is largely questionable and must all be restricted to clinical trials. Possible future therapeutic strategies include epidermal growth factor receptor inhibitors, antivascular endothelial growth factor therapies, cyclin D inhibitors, and HMG-CoA reductase inhibitors.
- Published
- 2007
- Full Text
- View/download PDF
45. Management of digestive bleeding related to portal hypertension in cirrhotic patients: A French multicenter cross-sectional practice survey.
- Author
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Ingrand P, Gournay J, Bernard P, Oberti F, Bernard-Chabert B, Pauwels A, Renard P, Bartoli E, Cadranel JF, Barbare JC, Ingrand I, and Beauchant M
- Subjects
- Adrenergic beta-Antagonists therapeutic use, Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Female, France, Gastrointestinal Hemorrhage physiopathology, Health Care Surveys, Humans, Hypertension, Portal drug therapy, Hypertension, Portal physiopathology, Hypertension, Portal prevention & control, Ligation, Liver Cirrhosis diagnosis, Liver Cirrhosis physiopathology, Male, Middle Aged, Practice Guidelines as Topic, Practice Patterns, Physicians', Prospective Studies, Vasoconstrictor Agents therapeutic use, Gastrointestinal Hemorrhage etiology, Gastrointestinal Hemorrhage therapy, Guideline Adherence, Hypertension, Portal complications, Liver Cirrhosis complications
- Abstract
Aim: To investigate the conformity of management practices of gastrointestinal hemorrhage in cirrhotic patients with relevant guidelines., Methods: A questionnaire on the management of digestive bleeding was completed for all consecutive cirrhotic patients admitted to 31 French hospitals., Results: One hundred and twenty-six bleeding events were recorded. It was the first bleeding episode in 79 patients (63%), of whom 40 (51%) had a prior diagnosis of cirrhosis and 25 (32%) had previously undergone an endoscopy. The bleeding episode was a recurrence in 46 patients (37%). The median time between onset and admission was 4 h, but exceeded 12 h in 42% of cases. There was an agreement between centers for early vasoactive drug administration (87% of cases), association with ligation (42%) more often than sclerosis (21%) at initial endoscopy, and antibiotic prophylaxis (64%). By contrast, prescription of beta-blockade alone or in combination (0 to 100%, P = 0.003) for secondary prophylaxis and lactulose (26% to 86%, P = 0.04), differed among centers., Conclusion: In French hospitals, management of bleeding related to portal hypertension in cirrhotic patients is generally in keeping with the consensus. Broad variability still remains concerning beta-blockade use for secondary prophylaxis. Screening for esophageal varices, the use of antibiotic prophylaxis and patients information need to be improved.
- Published
- 2006
- Full Text
- View/download PDF
46. [What changes were made in the National Thesaurus of Gastrointestinal Cancer in 2005?].
- Author
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Legoux JL, Bedenne L, Seitz JF, Pezet D, Rougier P, Bouché O, Barbare JC, André T, Malka D, Cadiot G, Ruskoné-Foumestraux A, Landi B, Peiffert D, Ducreux M, Louvet C, and Dorval E
- Subjects
- Carcinoma, Hepatocellular drug therapy, Clinical Trials as Topic, Clinical Trials, Phase II as Topic, Esophageal Neoplasms therapy, France, Gastrointestinal Neoplasms pathology, Gastrointestinal Neoplasms surgery, Gastrointestinal Stromal Tumors therapy, Humans, Liver Neoplasms drug therapy, Neoplasm Staging, Practice Guidelines as Topic, Randomized Controlled Trials as Topic, Stomach Neoplasms therapy, Adenocarcinoma drug therapy, Bile Duct Neoplasms therapy, Carcinoma, Hepatocellular therapy, Gastrointestinal Neoplasms therapy, Liver Neoplasms therapy, Pancreatic Neoplasms therapy, Vocabulary, Controlled
- Published
- 2006
- Full Text
- View/download PDF
47. Medical treatments for hepatocellular carcinoma (HCC): what's next?
- Author
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Taieb J, Barbare JC, and Rougier P
- Subjects
- Carcinoma, Hepatocellular diagnosis, Humans, Liver Neoplasms diagnosis, Carcinoma, Hepatocellular therapy, Liver Neoplasms therapy
- Published
- 2006
- Full Text
- View/download PDF
48. Hepatocellular carcinoma (primary cancer of the liver).
- Author
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Barbare JC, Boige V, Boudjema K, Lescesne R, and Trinchet JC
- Subjects
- Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chemoembolization, Therapeutic, Clinical Trials as Topic, France, Hepatectomy methods, Humans, Iodized Oil therapeutic use, Liver Transplantation, Palliative Care methods, Risk Factors, Carcinoma, Hepatocellular diagnosis, Carcinoma, Hepatocellular therapy, Liver Neoplasms diagnosis, Liver Neoplasms therapy, Practice Guidelines as Topic
- Published
- 2006
49. [Acute colitis closely following the beginning of celecoxib treatment].
- Author
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Houmani Z, Imbert A, Duchmann JC, Messerschmitt C, Barbare JC, Latrive JP, and Biour M
- Subjects
- Acute Disease, Aged, 80 and over, Alanine Transaminase blood, Anti-Inflammatory Agents, Non-Steroidal administration & dosage, Back Pain drug therapy, Celecoxib, Diarrhea chemically induced, Female, Humans, Pyrazoles administration & dosage, Sulfonamides administration & dosage, Anti-Inflammatory Agents, Non-Steroidal adverse effects, Colitis chemically induced, Pyrazoles adverse effects, Sulfonamides adverse effects
- Abstract
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.
- Published
- 2005
- Full Text
- View/download PDF
50. Randomized controlled trial of tamoxifen in advanced hepatocellular carcinoma.
- Author
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Barbare JC, Bouché O, Bonnetain F, Raoul JL, Rougier P, Abergel A, Boige V, Denis B, Blanchi A, Pariente A, Milan C, and Bedenne L
- Subjects
- Aged, Antineoplastic Agents, Hormonal adverse effects, Carcinoma, Hepatocellular mortality, Female, Humans, Liver Neoplasms mortality, Male, Middle Aged, Quality of Life, Survival Rate, Tamoxifen adverse effects, Antineoplastic Agents, Hormonal therapeutic use, Carcinoma, Hepatocellular drug therapy, Liver Neoplasms drug therapy, Tamoxifen therapeutic use
- Abstract
Purpose: Randomized studies on tamoxifen treatment of hepatocellular carcinoma (HCC) produced conflicting results. The aim of this study was to assess the efficacy of tamoxifen administration in improving overall survival of patients with advanced HCC., Patients and Methods: A total of 420 patients with HCC who were not suitable for surgery or local treatment were randomly assigned between April 1995 and May 2000: 210 in the control group and 210 in the tamoxifen group (20 mg/d orally). Patients with WHO performance status greater than 2, belonging to Child-Pugh class C, or with serum creatinine greater than 130 mumol/L were not eligible., Results: Tolerance was good and the main reported adverse effects were thrombophlebitis (three patients), nausea (two patients), and hot flushes (three patients). Outcome did not differ between the two treatment arms: estimated median survival was 4.8 and 4.0 months in the tamoxifen and in the control groups, respectively (P = .25). Univariate analysis showed significant association of survival with age, Okuda stage, WHO performance status, Child-Pugh class, intrahepatic tumor stage, alpha-fetoprotein serum concentration, and presence of extrahepatic spread, portal vein thrombosis, hepatomegaly, or hepatalgia. In a Cox proportional hazards model we found a significant beneficial effect of tamoxifen on survival in patients belonging to Okuda I or II stages., Conclusion: In this large study, tamoxifen did not improve the survival of patients with advanced HCC, but there is a suggestion that patients without major hepatic insufficiency seem to have some survival benefit. New trials involving this specific population are warranted.
- Published
- 2005
- Full Text
- View/download PDF
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