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1. Surgical closure, mainly with glue injection and anti-tumour necrosis factor alpha, in fistulizing perianal Crohn's disease: A multicentre randomized controlled trial

Author

Dominique Bouchard, Béatrice Vinson Bonnet, Guillaume Meurette, Cécile Train, Charlène Brochard, Pauline Roumeguère, Laurent Siproudhis, Laurent Abramowitz, Jean Marie Fayette, François Pigot, Ghislain Staumont, Hélène Pillant, Guillaume Bonnaud, A. Senéjoux, Jean Luc Faucheron, AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], Centre d'Investigation Clinique [Rennes] (CIC), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Maison de Santé Protestante de Bordeaux-Bagatelle (MSPB), Clinique Tivoli Ducos [Bordeaux], Hôpital Léopold-Bellan, CHI Poissy-Saint-Germain, Centre Hospitalier Universitaire [Grenoble] (CHU), CHP Saint Grégoire, Hôpital Ambroise Paré [AP-HP], Centre hospitalier universitaire de Nantes (CHU Nantes), ClinSearch [Malakoff, France], Clinique Saint-Jean Languedoc [Toulouse] (CSJL), Abbvie Laboratory AbbVie, and Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, Fistula, [SDV]Life Sciences [q-bio], fistulizing perianal, law.invention, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, Randomized controlled trial, law, medicine, Adalimumab, Humans, Rectal Fistula, Abscess, GLUE, Perianal Crohn's disease, Crohn's disease, business.industry, Anti tumour necrosis factor, Gastroenterology, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, surgical closure, 3. Good health, Surgery, seton removal, Treatment Outcome, 030220 oncology & carcinogenesis, Drainage, 030211 gastroenterology & hepatology, business, medicine.drug
Abstract

Clinical trial registration: ClinicalTrials.gov Identifier NCT01388257; International audience; Aim In patients with fistulizing perianal Crohn's disease (CD), the need for a secondary surgical step is not defined. The aim was to assess the efficacy of surgical closure compared to a single seton removal in patients with drained fistulizing perianal CD treated with adalimumab. Methods This was a multicentre, randomized controlled trial, comparing seton removal + surgical closure (closure group) to seton removal alone (control group) with a stratification according to the American Gastroenterological Association classification. The primary end-point was fistula closure at month 12 defined by the association of the following criteria: no seton, absence of a visible external opening, absence of discharge from the tract after finger compression, absence of an internal opening, absence of perianal pain/abscess and absence of fistula-related abnormalities. Results Among the 64 included patients (262 expected) (48 complex fistula, 75%), 33 were randomized to the closure group and 31 to the control group. In the closure group, 26 patients (78.8%) had glue. At month 12, overall fistula closure was achieved in 35 of the evaluable 58 patients (60%): 18/32 (56%) in the surgery group and 17/26 (65%) in the control group (P = 0.479). In the closure group, fistula closure was observed in 13/25 (52%) and 5/7 (71%) patients with complex and simple fistula respectively (P = 0.426), compared with 12/18 (67%) and 5/8 (63%), respectively in the control group (P = 1.000). Conclusions Seton removal alone seems to be no more effective than a secondary surgical step (in particular glue injection) in patients having fistulizing perianal CD controlled by an initial drainage combined with adalimumab. The results should be interpreted with caution.

Published
2021
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2. Early evaluation using a radiomic signature of unresectable hepatic metastases to predict outcome in patients with colorectal cancer treated with FOLFIRI and bevacizumab

Author

Anthony, Dohan, Benoit, Gallix, Boris, Guiu, Karine, Le Malicot, Caroline, Reinhold, Philippe, Soyer, Jaafar, Bennouna, Francois, Ghiringhelli, Emilie, Barbier, Valérie, Boige, Julien, Taieb, Olivier, Bouché, Eric, François, Jean-Marc, Phelip, Christian, Borel, Roger, Faroux, Jean-Francois, Seitz, Stéphane, Jacquot, Meher, Ben Abdelghani, Faiza, Khemissa-Akouz, Dominique, Genet, Jean Louis, Jouve, Yves, Rinaldi, Françoise, Desseigne, Patrick, Texereau, Etienne, Suc, Come, Lepage, Thomas, Aparicio, Christine, Hoeffel, Zied, Ladhib, Service de Radiologie [CHU Cochin], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), McGill University Health Center [Montreal] (MUHC), l'Institut de Recherche contre les Cancers de l'Appareil Digestif (IRCAD), CHU Strasbourg, Département radiologie diagnostique et interventionnelle Saint Eloi [CHRU Montpellier], Pôle Digestif [CHRU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Fédération Francophone de la Cancérologie Digestive, FFCD, Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER, Equipe EPICAD (LNC - U1231), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut Gustave Roussy (IGR), Oncologie digestive, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Université de Paris - UFR Médecine Paris Centre [Santé] (UP Médecine Paris Centre), Université de Paris (UP), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre Paul Strauss, CRLCC Paul Strauss, Service de chirurgie digestive (CH de La Roche-sur-Yon), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Service d'oncologie digestive et hépato-gastro-entérologie [Hôpital de la Timone - APHM], Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Centre de Cancérologie du Grand Montpellier (CCGM), Centre Hospitalier Saint Jean de Perpignan, Polyclinique de Limoges - site François Chénieux [Limoges], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Européen [Fondation Ambroise Paré - Marseille], Centre Léon Bérard [Lyon], CHU Mont de Marsan, Clinique Saint-Jean Languedoc [Toulouse] (CSJL), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Centre de Recherche en Sciences et Technologies de l'Information et de la Communication - EA 3804 (CRESTIC), Université de Reims Champagne-Ardenne (URCA), and Hôpital Maison Blanche

Subjects
Male, Oncology, Colorectal cancer, medicine.medical_treatment, Leucovorin, Kaplan-Meier Estimate, 030218 nuclear medicine & medical imaging, MESH: Camptothecin / administration & dosage, Camptothecin / analogs & derivatives, Colorectal Neoplasms / drug therapy, Colorectal Neoplasms / pathology, Computational Biology, Female, 0302 clinical medicine, Antineoplastic Combined Chemotherapy Protocols, Prospective Studies, Prospective cohort study, Aged, 80 and over, Liver Neoplasms, Gastroenterology, MESH: Radiographic Image Interpretation, Computer-Assisted, Response Evaluation Criteria in Solid Tumors, Survival Rate, Tomography, X-Ray Computed, Middle Aged, Bevacizumab, 030220 oncology & carcinogenesis, Cohort, FOLFIRI, Radiographic Image Interpretation, Computer-Assisted, Fluorouracil, Colorectal Neoplasms, Clinical decision making, medicine.drug, Adult, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, MESH: Fluorouracil / administration & dosage, Humans, Leucovorin / administration & dosage, Liver Neoplasms / diagnostic imaging, Computerised image analysis, 03 medical and health sciences, Colorectal metastases, MESH: Adult, Antineoplastic Combined Chemotherapy Protocols / administration & dosage, Bevacizumab / administration & dosage, Camptothecin / administration & dosage, Predictive Value of Tests, Internal medicine, [INFO.INFO-IM]Computer Science [cs]/Medical Imaging, medicine, Chemotherapy, MESH: Liver Neoplasms / secondary, Aged, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, medicine.disease, Log-rank test, Irinotecan, Camptothecin, business
Abstract

PurposeThe objective of this study was to build and validate a radiomic signature to predict early a poor outcome using baseline and 2-month evaluation CT and to compare it to the RECIST1·1 and morphological criteria defined by changes in homogeneity and borders.MethodsThis study is an ancillary study from the PRODIGE-9 multicentre prospective study for which 491 patients with metastatic colorectal cancer (mCRC) treated by 5-fluorouracil, leucovorin and irinotecan (FOLFIRI) and bevacizumab had been analysed. In 230 patients, computed texture analysis was performed on the dominant liver lesion (DLL) at baseline and 2 months after chemotherapy. RECIST1·1 evaluation was performed at 6 months. A radiomic signature (Survival PrEdiction in patients treated by FOLFIRI and bevacizumab for mCRC using contrast-enhanced CT TextuRe Analysis (SPECTRA) Score) combining the significant predictive features was built using multivariable Cox analysis in 120 patients, then locked, and validated in 110 patients. Overall survival (OS) was estimated with the Kaplan-Meier method and compared between groups with the logrank test. An external validation was performed in another cohort of 40 patients from the PRODIGE 20 Trial.ResultsIn the training cohort, the significant predictive features for OS were: decrease in sum of the target liver lesions (STL), (adjusted hasard-ratio(aHR)=13·7, p=1·93×10–7), decrease in kurtosis (ssf=4) (aHR=1·08, p=0·001) and high baseline density of DLL, (aHR=0·98, p0·02 had a lower OS in the training cohort (pConclusionA radiomic signature (combining decrease in STL, density and computed texture analysis of the DLL) at baseline and 2-month CT was able to predict OS, and identify good responders better than RECIST1.1 criteria in patients with mCRC treated by FOLFIRI and bevacizumab as a first-line treatment. This tool should now be validated by further prospective studies.Trial registrationClinicaltrial.gov identifier of the PRODIGE 9 study: NCT00952029.Clinicaltrial.gov identifier of the PRODIGE 20 study: NCT01900717.

Published
2019
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3. Factors Affecting Tamoxifen Metabolism in Patients With Breast Cancer: Preliminary Results of the French PHACS Study

Author

Jacques Robert, Alicja Puszkiel, Alexandre Evrard, Etienne Chatelut, Florence Dalenc, Marc Debled, Fabienne Thomas, Caroline Delmas, Laurence Venat-Bouvet, Isabelle Sillet-Bach, Henri Roché, Thomas Filleron, Christelle Vachoux, Etienne Suc, Cécile Arellano, Jean-Christophe Boyer, Valérie Le Morvan, Melanie White-Koning, William Jacot, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Biochimie [CHRU Nîmes], Centre Hospitalier Régional Universitaire de Nîmes (CHRU Nîmes), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié - CRLCC Bordeaux, CRLCC Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Oncologie médicale [CHU Limoges], CHU Limoges, Clinique Saint Jean Languedoc, Centre Hospitalier Brive-la-Gaillarde, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Institut Bergonié [Bordeaux], UNICANCER, Institut Claudius Regaud, and Clinique Saint-Jean Languedoc [Toulouse] (CSJL)

Subjects
Oncology, Adult, medicine.medical_specialty, CYP2D6, CYP2B6, Antineoplastic Agents, Hormonal, Genotype, Breast Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, CYP2C19, 030226 pharmacology & pharmacy, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Breast cancer, Pharmacokinetics, Cytochrome P-450 Enzyme System, Internal medicine, medicine, Cytochrome P-450 CYP3A, Humans, Pharmacology (medical), Prospective Studies, skin and connective tissue diseases, Aged, Pharmacology, CYP3A4, business.industry, Middle Aged, medicine.disease, 3. Good health, Cytochrome P-450 CYP2B6, Tamoxifen, Cytochrome P-450 CYP2D6, Pharmacogenetics, 030220 oncology & carcinogenesis, Cytochrome P-450 CYP2C19 Inhibitors, Female, business, medicine.drug
Abstract

International audience; In addition to the effect of cytochrome P450 (CYP) 2D6 genetic polymorphisms, the metabolism of tamoxifen may be impacted by other factors with possible consequences on therapeutic outcome (efficacy and toxicity). This analysis focused on the pharmacokinetic (PK)-pharmacogenetic evaluation of tamoxifen in 730 patients with adjuvant breast cancer included in a prospective multicenter study. Plasma concentrations of tamoxifen and six major metabolites, the genotype for 63 single-nucleotide polymorphisms, and comedications were obtained 6 months after treatment initiation. Plasma concentrations of endoxifen were significantly associated with CYP2D6 diplotype (P

Published
2019
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4. Management of anoperineal lesions in Crohn’s disease: a French National Society of Coloproctology national consensus

Author

F. Pigot, Paul Benfredj, B. Vinson-Bonnet, T. Higuero, Jean-Luc Faucheron, Yves Panis, David Laharie, Dominique Bouchard, Nadia Fathallah, Charlène Brochard, Laurent Siproudhis, Laurent Abramowitz, Ghislain Staumont, V. de Parades, Maison de Santé Protestante Bagatelle, Clinique Saint Jean Languedoc, Foie, métabolismes et cancer, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Hôpital Bichat - Claude Bernard, CHU Pontchaillou [Rennes], Centre Hospitalier Universitaire [Grenoble] (CHU), Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Université Joseph Fourier - Grenoble 1 (UJF)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP)-IMAG-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon, Institut de Proctologie Léopold bellan, Groupe Hospitalier Paris Saint-Joseph, CHI Poissy-Saint-Germain, Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Clinique Saint-Jean Languedoc [Toulouse] (CSJL), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Groupe Hospitalier Paris Saint-Joseph (hpsj)

Subjects
Male, Anal fistula, Crohn’s disease, medicine.medical_specialty, Consensus, [SDV]Life Sciences [q-bio], Anal Canal, Disease, Perineum, 03 medical and health sciences, 0302 clinical medicine, Crohn Disease, medicine, Humans, Rectal Fistula, Societies, Medical, ComputingMilieux_MISCELLANEOUS, Anus Diseases, Crohn's disease, business.industry, General surgery, Gastroenterology, Disease Management, medicine.disease, Abscess, Colorectal surgery, 3. Good health, Treatment, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Treatment strategy, Female, 030211 gastroenterology & hepatology, Surgery, France, business, Colorectal Surgery, Algorithms, Abdominal surgery
Abstract

The French National Society of Coloproctology established national recommendations for the treatment of anoperineal lesions associated with Crohn's disease. Treatment strategies for acute abscesses, active fistulas (active denovo and still active under treatment), fistulas in remission, and rectovaginal fistulas are suggested. Recommendations have been graded following the international recommendations, and when absent, professional agreement has been established. For each situation, practical algorithms have been drawn.

Published
2018
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5. Double deletion of a chromosome 21 inserted in a chromosome 22 in an azoospermic patient

Author

Dominique Bourgeois, Philippe De Mas, Laurence Bouneau, Romain Molignier, Patrick Calvas, Valentine Marquet, Adeline Vigouroux-Castera, Hôpital Purpan [Toulouse], CHU Toulouse [Toulouse], and Clinique Saint-Jean Languedoc [Toulouse] (CSJL)

Subjects
Derivative chromosome, Case Reports, Biology, partial monosomy 21, insertion, 03 medical and health sciences, Chromosome 15, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, medicine, chromosome, deletion, Azoospermia, 030304 developmental biology, Chromosome 7 (human), Genetics, 0303 health sciences, 030305 genetics & heredity, Karyotype, deletion, chromosome, General Medicine, medicine.disease, chromosome 22, karyotype, Chromosome 17 (human), chromosome 21, Chromosome 21, Chromosome 22
Abstract

International audience; We report on a phenotypically normal 41-year-old azoospermic man with a 45 chromosomes karyotype including one normal chromosome 21, one normal chromosome 22, and a der(22)ins(22;21). Array CGH showed a 1.8 Mb terminal deletion of bands 21pter to 21q21.1 and a 341 kb terminal deletion on band 21q22.3.

Published
2015
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6. Bevacizumab Maintenance Versus No Maintenance During Chemotherapy-Free Intervals in Metastatic Colorectal Cancer: A Randomized Phase III Trial (PRODIGE 9)

Author

Stephane Jacquot, Karine Le Malicot, Christian Borel, Julien Taieb, Valérie Boige, Thomas Aparicio, Jean-Marc Phelip, Dominique Genet, Jaafar Bennouna, Laetitia Dahan, Roger Faroux, Etienne Suc, Faiza Khemissa, E. Francois, Côme Lepage, Prodige Investigators, François Ghiringhelli, Patrick Texereau, Françoise Desseigne, Olivier Bouché, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Sorbonne Paris Cité (USPC), Service de Médecine Nucléaire, Centre Georges-François Leclerc [Dijon] (CGFL), Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER, Institut Gustave Roussy (IGR), Fédération Francophone de la Cancérologie Digestive, FFCD, Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Centre Hospitalier Universitaire de Reims (CHU Reims), Centre Hospitalier Universitaire de Saint-Etienne (CHU de Saint-Etienne), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, CRLCC Paul Strauss, Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon, Hôpital de la Timone [CHU - APHM] (TIMONE), Institut de Recherche en Cancérologie de Montpellier (IRCM - U1194 Inserm - UM), CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Polyclinique de Limoges - Site Émailleurs-Colombier [Limoges], Centre Hospitalier Saint Jean de Perpignan, Clinique Saint-Jean Languedoc [Toulouse] (CSJL), Centre Léon Bérard [Lyon], CHU Mont de Marsan, CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, université de Bourgogne, LNC, UNICANCER-Université Côte d'Azur (UCA), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), CHU Saint Louis [APHP], Université Sorbonne Paris Cité ( USPC ), Service de Médecine Nucléaire, Centre Georges-François Leclerc [Dijon] ( CGFL ), Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc ( CRLCC - CGFL ), Institut Gustave Roussy ( IGR ), Hôpital Européen Georges Pompidou [APHP] ( HEGP ), Centre Hospitalier Universitaire de Reims ( CHU Reims ), Centre Hospitalier Universitaire de Saint-Etienne ( CHU de Saint-Etienne ), CRLCC Antoine Lacassagne, Hôpital de la Timone [CHU - APHM] ( TIMONE ), Institut de recherche en cancérologie de Montpellier ( IRCM ), Université Montpellier 1 ( UM1 ) -CRLCC Val d'Aurelle - Paul Lamarque-Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université de Montpellier ( UM ), Clinique Saint Jean Languedoc, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand ( CHU Dijon ), Lipides - Nutrition - Cancer [Dijon - U1231] ( LNC ), Université de Bourgogne ( UB ) -AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale ( INSERM ), and Institut de Cancérologie de l'Ouest

Subjects
0301 basic medicine, Oncology, Male, Cancer Research, medicine.medical_specialty, Time Factors, Bevacizumab, Colorectal cancer, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Disease-Free Survival, [ SDV.CAN ] Life Sciences [q-bio]/Cancer, law.invention, 03 medical and health sciences, 0302 clinical medicine, Antineoplastic Agents, Immunological, [SDV.CAN] Life Sciences [q-bio]/Cancer, Randomized controlled trial, law, Internal medicine, medicine, Humans, Neoplasm Metastasis, Aged, Chemotherapy, business.industry, Induction chemotherapy, Induction Chemotherapy, Middle Aged, medicine.disease, 3. Good health, Irinotecan, Regimen, 030104 developmental biology, Fluorouracil, 030220 oncology & carcinogenesis, Female, business, Colorectal Neoplasms, Metastatic Colorectal Cancer, medicine.drug
Abstract

Purpose Conflicting results are reported for maintenance treatment with bevacizumab during chemotherapy-free intervals (CFI) in metastatic colorectal cancer after induction chemotherapy. Patients and Methods In this open-label, phase III, randomized controlled trial, we compared the tumor control duration (TCD) observed with bevacizumab maintenance and with no treatment (observation) during CFI subsequent to induction chemotherapy with 12 cycles of fluorouracil, leucovorin, and irinotecan plus bevacizumab. After disease progression, the induction regimen was repeated for eight cycles, followed by a new CFI. Results From March 2010 to July 2013, 491 patients were randomly assigned. Disease progression or death occurred during induction chemotherapy in 85 patients (17%); 261 patients (53%) had at least one reinduction, 107 (22%) had two reinductions, and 56 (11%) had three or more reinductions. The median TCD was 15 months in both groups; the median progression-free survival (PFS) from randomization was 9.2 and 8.9 months in the maintenance group and observation groups, respectively. The TCD observed in both groups was higher compared with the TCD hypotheses of the trial. The median overall survival (OS) was 21.7 and 22.0 months in the maintenance and observation groups, respectively. In the per-protocol population, defined as patients with at least one reinduction after the first progression, the median duration of the first CFI was 4.3 months in both arms; the median TCD was 17.8 and 23.3 months ( P = .339), the median PFS was 9.9 and 9.5 months, and the median OS was 27.6 and 28.5 months in the maintenance and observation groups, respectively. Multivariable analysis revealed that female gender, WHO performance status ≥ 2, and unresected primary tumors were associated with a shorter TCD. Conclusion Bevacizumab maintenance monotherapy did not improve TCD, CFI duration, PFS, or OS.

Published
2018
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7. Anoperineal lesions in Crohn’s disease: French recommendations for clinical practice

Author

Laurent Siproudhis, Ghislain Staumont, A. Senéjoux, Yves Panis, Léon Maggiori, Charlène Brochard, Guillaume Bouguen, M. Eleouet-Kaplan, Nadia Fathallah, F. Pigot, J.-M. Suduca, B. Vinson-Bonnet, V. de Parades, Jean-Luc Faucheron, Jean-David Zeitoun, Alain Dabadie, P. Roumeguère, Laurent Abramowitz, Dominique Bouchard, Maison de Santé Protestante Bagatelle, Hôpital Bichat - Claude Bernard, CHU Pontchaillou [Rennes], Institut de Proctologie Léopold bellan, Groupe Hospitalier Paris Saint-Joseph (hpsj), CHU Grenoble, Gestes Medico-chirurgicaux Assistés par Ordinateur (TIMC-IMAG-GMCAO), Techniques de l'Ingénierie Médicale et de la Complexité - Informatique, Mathématiques et Applications, Grenoble - UMR 5525 (TIMC-IMAG), Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP )-VetAgro Sup - Institut national d'enseignement supérieur et de recherche en alimentation, santé animale, sciences agronomiques et de l'environnement (VAS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Clinique Tivoli Ducos [Bordeaux], CHP Saint Grégoire, Foie, métabolismes et cancer, Université de Rennes (UR)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), Clinique Saint-Jean Languedoc [Toulouse] (CSJL), CHI Poissy-Saint-Germain, Groupe Hospitalier Diaconesses Croix Saint-Simon, Groupe Hospitalier Paris Saint-Joseph, Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Structure Fédérative de Recherche en Biologie et Santé de Rennes ( Biosit : Biologie - Santé - Innovation Technologique ), and Jonchère, Laurent

Subjects
Male, Crohn’s disease, medicine.medical_treatment, Fistula, Anal Canal, Recommendations, Perineum, 0302 clinical medicine, Crohn Disease, Anal stenosis, Digestive System Surgical Procedures, Crohn's disease, medicine.diagnostic_test, Gastroenterology, Colostomy, Anal fistulas, Anus Neoplasms, Combined Modality Therapy, Colorectal surgery, Abscess, 3. Good health, Treatment Outcome, 030220 oncology & carcinogenesis, Practice Guidelines as Topic, Drainage, Female, 030211 gastroenterology & hepatology, France, Adult, Anal fistula, medicine.medical_specialty, Consensus, Anoperineal lesions, Physical examination, Guidelines, 03 medical and health sciences, Gastrointestinal Agents, medicine, Humans, Rectal Fistula, Tumor Necrosis Factor-alpha, business.industry, [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Evidence-based medicine, medicine.disease, [SDV.MHEP.HEG] Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology, Surgery, business
Abstract

International audience; Background: Anoperineal lesion (APL) occurrence is a significant event in the evolution of Crohn’s disease (CD). Management should involve a multidisciplinary approach combining the knowledge of the gastroenterologist, the colorectal surgeon and the radiologist who have appropriate experience in this area. Given the low level of evidence of available medical and surgical strategies, the aim of this work was to establish a French expert consensus on management of anal Crohn’s disease. These recommendations were led under the aegis of the Société Nationale Française de Colo-Proctologie (SNFCP). They report a consensus on the management of perianal Crohn’s disease lesions, including fistulas, ulceration and anorectal stenosis and propose an appropriate treatment strategy, as well as sphincter-preserving and multidisciplinary management.Methodology: A panel of French gastroenterologists and colorectal surgeons with expertise in inflammatory bowel diseases reviewed the literature in order to provide practical management pathways for perianal CD. Analysis of the literature was made according to the recommendations of the Haute Autorité de Santé (HAS) to establish a level of proof for each publication and then to propose a rank of recommendation. When lack of factual data precluded ranking according to the HAS, proposals based on expert opinion were written. Therefore, once all the authors agreed on a consensual statement, it was then submitted to all the members of the SNFCP. As initial literature review stopped in December 2014, more recent European or international guidelines have been published since and were included in the analysis.Results: MRI is recommended for complex secondary lesions, particularly after failure of previous medical and/or surgical treatments. For severe anal ulceration in Crohn’s disease, maximal medical treatment with anti-TNF agent is recommended. After prolonged drainage of simple anal fistula by a flexible elastic loop or loosely tied seton, and after obtaining luminal and perineal remission by immunosuppressive therapy and/or anti-TNF agents, the surgical treatment options to be discussed are simple seton removal or injection of the fistula tract with biological glue. After prolonged loose-seton drainage of the complex anal fistula in Crohn’s disease, and after obtaining luminal and perineal remission with anti-TNF ± immunosuppressive therapy, surgical treatment options are simple removal of seton and rectal advancement flap. Colostomy is indicated as a last option for severe APL, possibly associated with a proctectomy if there is refractory rectal involvement after failure of other medical and surgical treatments. The evaluation of anorectal stenosis of Crohn’s disease (ARSCD) requires a physical examination, sometimes under anesthesia, plus endoscopy with biopsies and MRI to describe the stenosis itself, to identify associated inflammatory, infectious or dysplastic lesions, and to search for injury or fibrosis of the sphincter. Therapeutic strategy for ARSCD requires medical–surgical cooperation.

Published
2017
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8. Poorly differentiated gastro-entero-pancreatic neuroendocrine carcinomas: Are they really heterogeneous? Insights from the FFCD-GTE national cohort

Author

Sylvain Manfredi, Eric Terrebonne, Gael Deplanque, Jean-Yves Scoazec, Anne-Laure Ran-Royo, Marc Ferec, Guillaume Cadiot, Eric Maringe, C. Desauw, Philippe Rougier, Thomas Aparicio, Castex, Guillaume Geslin, Jean-François Seitz, François Dewaele, Karine Bouhier-Leporrier, Vincent Hautefeuille, Anne Thirot-Bidault, Olivia Hentic, G. Roquin, David Tougeron, Olivier Dubreuil, C. Rebischung, Laetitia Dahan, Ivan Borbath, Jean-Louis Legoux, Laurent Bedenne, Sandrine Lavau denes, Catherine Ligeza, Mathieu Baconnier, K. Le Malicot, Laurent Cany, Côme Lepage, Thierry Lecomte, Céline Lepère, I. Bonnet, Valérie Rossi, Isabelle Wanicki Caron, Laetitia Stephanie, Cedric Lecaille, Eric Baudin, Thomas Walter, David Malka, Patricia Niccoli, Vincent Bourgeois, Etienne Suc, Joël Guigay, Romain Coriat, Rosine Guimbaud, Catherine Lombard-Bohas, Caroline Petorin, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Poitiers (CHU Poitiers), Institut Gustave Roussy (IGR), Fédération Francophone de la Cancérologie Digestive, FFCD, CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Beaujon, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Pontchaillou [Rennes], CHU Valenciennes, CHU Toulouse [Toulouse], Hôpital Cochin [AP-HP], Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), CHU de Lille, Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Service de Gastro-entérologie [Avicenne], Université Paris 13 (UP13)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Hôpital de la source, CHU Lyon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Hôpital Robert Debré, Service d'Hépato-gastroentérologie, 51092 Reims, France, affiliation inconnue, CHU Estaing [Clermont-Ferrand], CHU Clermont-Ferrand, Hôpital Haut-Lévêque, Université Sciences et Technologies - Bordeaux 1-CHU Bordeaux [Bordeaux], Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Clinique Saint-Jean Languedoc [Toulouse] (CSJL), CHU Amiens-Picardie, Hôpital Duchenne, CH Boulogne sur Mer, Polyclinique Francheville, Centre Catherine-de-Sienne [Nantes] (CCS), Polyclinique Bordeaux Nord Aquitaine, Hôpital Michallon, CH du Haut Anjou (Château-Gontier), CH Annecy Genevois, CHU Pitié-Salpêtrière [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier du pays de Morlaix, Hôpital Saint-Joseph, Assistance Publique-Hôpitaux de Paris, Cabinet privé des Dr Geslin Provost (Vannes), CHU Rouen, Normandie Université (NU), CHU Dupuytren, CHU Dijon, Clinique Mutualiste de l'Estuaire (Saint Nazaire), Hospices Civils de Beaune [Centre hospitalier de Beaune], Centre de radiothérapie et d'oncologie médicale privée (Béziers), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), Hôpital Beaujon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), and Université Côte d'Azur (UCA)-UNICANCER

Subjects
Oncology, Male, Cancer Research, medicine.medical_specialty, 030209 endocrinology & metabolism, [SDV.CAN]Life Sciences [q-bio]/Cancer, Carboplatin, Cohort Studies, 03 medical and health sciences, Gastrointestinal cancer, 0302 clinical medicine, Internal medicine, Antineoplastic Combined Chemotherapy Protocols, medicine, FOLFIRI Regimen, Humans, Neoplasm Metastasis, Prospective cohort study, Aged, Etoposide, Gastrointestinal Neoplasms, Univariate analysis, Performance status, business.industry, Large cell, Hazard ratio, Ki67 index, medicine.disease, Prognosis, 3. Good health, Carcinoma, Neuroendocrine, Pancreatic Neoplasms, Treatment, Cell Transformation, Neoplastic, 030220 oncology & carcinogenesis, Neuroendocrine carcinoma, Female, Cisplatin, business, Cohort study
Abstract

IF 6.029; International audience; BackgroundDiagnosis and management of poorly differentiated gastro-entero-pancreatic (GEP) neuroendocrine carcinomas (NECs) remain challenging. Recent studies suggest prognostic heterogeneity. We designed within the French Group of Endocrine Tumours a prospective cohort to gain insight in the prognostic stratification and treatment of GEP-NEC.Patients and methodsAll patients with a diagnosis of GEP-NEC between 1st January 2010 and 31st December 2013 could be included in this national cohort. Adenoneuroendocrine tumours were excluded.Results253 patients from 49 centres were included. Median age was 66 years. Main primary locations were pancreas (21%), colorectal (27%), oesophagus-stomach (18%); primary location was unknown in 20%. Tumours were metastatic at diagnosis in 78% of cases. Performance status (PS) at diagnosis was 0–1 in 79% of patients. Among the 147 (58%) cases reviewed by an expert pathological network, 39% were classified as small cell NEC and 61% as large cell NEC. Median Ki67 index was 75% (range, 20–100). Median overall survival was 15.6 (13.6–17.0) months. Significant adverse prognostic factors in univariate analysis were PS > 1 (hazard ratio [HR] = 2.5), metastatic disease (HR = 1.6), NSE > 2 upper limit of normal [ULN]; HR = 3.2), CgA > 2 ULN (HR = 1.7) and lactate dehydrogenase >2 ULN (HR = 2.1). After first-line palliative chemotherapy (CT1) with platinum-etoposide (n = 152), objective response, progression-free survival and overall survival were 50%, 6.2 and 11.6 months; they were 24%, 2.9 and 5.9, respectively, after post-CT1 FOLFIRI regimen (n = 72).ConclusionsWe report a large prospective series of GEP-NEC which show the predominance of large cell type and advanced stage at diagnosis. Prognosis was found more homogeneous than previously reported, mainly impacted by PS and tumour burden.

Published
2017
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9. Prognostic Factors for Survival in Noncastrate Metastatic Prostate Cancer: Validation of the Glass Model and Development of a Novel Simplified Prognostic Model

Author

Claude El Kouri, Marjorie Baciuchka, Gael Deplanque, Michel Soulié, Loic Mourey, Jean-Pascal Machiels, Brigitte Laguerre, Jochen Walz, Jean-Marie Boher, Patricia Marino, Jean-Marc Ferrero, Guilhem Bousquet, Jérôme Dauba, Stéphane Oudard, Philippe Beuzeboc, Claude Linassier, Christine Theodore, Florence Joly, Ivan Krakowski, Frederic Rolland, Jean-François Berdah, Alain Ravaud, Karim Fizazi, Remy Delva, Gwenaelle Gravis, Muriel Habibian, Igor Latorzeff, Ali Hasbini, Damien Pouessel, Sylvie Zanetta, Christian Platini, Jean-Christophe Eymard, Jean-Luc Labourey, Etienne Suc, Franck Priou, Institut Paoli-Calmettes, Fédération nationale des Centres de lutte contre le Cancer (FNCLCC), Sciences Economiques et Sociales de la Santé & Traitement de l'Information Médicale (SESSTIM - U1252 INSERM - Aix Marseille Univ - UMR 259 IRD), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Université Paris-Sud - Paris 11 (UP11), Oncologie génito-urinaire, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Régional de Lutte contre le Cancer François Baclesse [Caen] (UNICANCER/CRLC), Normandie Université (NU)-UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN), Hôpital Côte de Nacre [CHU Caen], CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Centre Hospitalier Départemental - Hôpital de La Roche-sur-Yon (CHD Vendée), Clinique Pasteur [Toulouse], Centre Paul Papin, CRLCC Paul Papin, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre Eugène Marquis (CRLCC), CRLCC René Gauducheau, Hôpital Foch [Suresnes], Centre hospitalier Saint-Joseph [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), UNICANCER-Université Côte d'Azur (UCA), CRLC Val d'Aurelle-Paul Lamarque, CRLCC Val d'Aurelle - Paul Lamarque, Institut Claudius Regaud, Institut Curie [Paris], Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), Hôpital de Toulon/Hyères - Sainte Marguerite [Hyères] (HTH-SM), Centre Hospitalier Layné, Hôpital de la Timone [CHU - APHM] (TIMONE), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Hôpital Bretonneau, Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Hôpital Dupuytren [CHU Limoges], Université Catholique de Louvain = Catholic University of Louvain (UCL), Centre Catherine-de-Sienne [Nantes] (CCS), Hôpital Saint-André, Clinique Saint-Jean Languedoc [Toulouse] (CSJL), Institut Jean Godinot [Reims], Clinique Armoricaine de Radiologie [St. Brieuc], Hopital Saint-Louis [AP-HP] (AP-HP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Université Paris Descartes - Paris 5 (UPD5), UNICANCER-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU), CHD Vendée - Hôpital Les Oudairies [La Roche sur Yon], Centre Alexis Vautrin [Vandoeuvre-lès-Nancy], Université Côte d'Azur (UCA)-UNICANCER, Hôpital de Rangueil, CHU Toulouse [Toulouse], UCL - SSS/IREC/MIRO - Pôle d'imagerie moléculaire, radiothérapie et oncologie, UCL - (SLuc) Unité d'oncologie médicale, and Malbec, Odile

Subjects
Male, Oncology, Time Factors, [SDV]Life Sciences [q-bio], Kaplan-Meier Estimate, Docetaxel, Androgen deprivation therapy, Prostate cancer, Risk Factors, Antineoplastic Combined Chemotherapy Protocols, Medicine, Prospective Studies, 10. No inequality, 2. Zero hunger, education.field_of_study, Univariate analysis, Hazard ratio, Noncastrate, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Treatment Outcome, Lymphatic Metastasis, Metastatic, Taxoids, France, medicine.drug, medicine.medical_specialty, Antineoplastic Agents, Hormonal, Urology, Population, Bone Neoplasms, Adenocarcinoma, Prognostic factors, Risk Assessment, Decision Support Techniques, Predictive Value of Tests, Internal medicine, Alkaline phosphatase, Biomarkers, Tumor, Humans, education, Aged, Proportional Hazards Models, Performance status, business.industry, Prostatic Neoplasms, Reproducibility of Results, Androgen Antagonists, medicine.disease, Confidence interval, Surgery, Nomograms, business, Orchiectomy
Abstract

BACKGROUND: The Glass model developed in 2003 uses prognostic factors for noncastrate metastatic prostate cancer (NCMPC) to define subgroups with good, intermediate, and poor prognosis. OBJECTIVE: To validate NCMPC risk groups in a more recently diagnosed population and to develop a more sensitive prognostic model. DESIGN, SETTING, AND PARTICIPANTS: NCMPC patients were randomized to receive continuous androgen deprivation therapy (ADT) with or without docetaxel in the GETUG-15 phase 3 trial. Potential prognostic factors were recorded: age, performance status, Gleason score, hemoglobin (Hb), prostate-specific antigen, alkaline phosphatase (ALP), lactate dehydrogenase (LDH), metastatic localization, body mass index, and pain. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: These factors were used to develop a new prognostic model using a recursive partitioning method. Before analysis, the data were split into learning and validation sets. The outcome was overall survival (OS). RESULTS AND LIMITATIONS: For the 385 patients included, those with good (49%), intermediate (29%), and poor (22%) prognosis had median OS of 69.0, 46.5 and 36.6 mo (p=0.001), and 5-yr survival estimates of 60.7%, 39.4%, and 32.1%, respectively (p=0.001). The most discriminatory variables in univariate analysis were ALP, pain intensity, Hb, LDH, and bone metastases. ALP was the strongest prognostic factor in discriminating patients with good or poor prognosis. In the learning set, median OS in patients with normal and abnormal ALP was 69.1 and 33.6 mo, and 5-yr survival estimates were 62.1% and 23.2%, respectively. The hazard ratio for ALP was 3.11 and 3.13 in the learning and validation sets, respectively. The discriminatory ability of ALP (concordance [C] index 0.64, 95% confidence interval [CI] 0.58-0.71) was superior to that of the Glass risk model (C-index 0.59, 95% CI 0.52-0.66). The study limitations include the limited number of patients and low values for the C-index. CONCLUSION: A new and simple prognostic model was developed for patients with NCMPC, underlying the role of normal or abnormal ALP. PATIENT SUMMARY: We analyzed clinical and biological factors that could affect overall survival in noncastrate metastatic prostate cancer. We showed that normal or abnormal alkaline phosphatase at baseline might be useful in predicting survival.

Published
2015
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10. Recommendations Endoscopy in inflammatory bowel disease: recommendations from the IBD Committee of the French Society of Digestive Endoscopy (SFED)

Author

Florent Gonzalez, Arnaud Bourreille, David Bernardini, Lucine Vuitton, Jérôme Filippi, Guillaume Bonnaud, David Laharie, Jean-Baptiste Chevaux, Philippe Bulois, Laurent Peyrin-Biroulet, Stéphane Koch, Caroline Trang, Patrick Faure, Christophe Cellier, Nutrition-Génétique et Exposition aux Risques Environnementaux (NGERE), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Service d'Hépato-gastro-entérologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Clinique des cèdres, Institut des Maladies de l'Appareil Digestif, Université de Nantes (UN), Clinique Saint-Jean Languedoc [Toulouse] (CSJL), Hépato-Gastroentérologie, Centre Hospitalier Universitaire de Nice (CHU Nice), Service d'hépato-gastro-entérologie, CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], Service de Gastro-Entérologie [CHRU Besançon], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de gastroentérologie [Polyclinique du Grand Sud Nîmes], Polyclinique du Grand Sud [Nîmes], Centre Hospitalier Intercommunal Toulon-La Seyne sur Mer - Hôpital Sainte-Musse, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)

Subjects
medicine.medical_specialty, medicine.diagnostic_test, business.industry, General surgery, [SDV]Life Sciences [q-bio], Gastroenterology, medicine.disease, Inflammatory bowel disease, 3. Good health, Endoscopy, 03 medical and health sciences, Digestive endoscopy, 0302 clinical medicine, inflammatory bowel disease, 030220 oncology & carcinogenesis, Internal medicine, Medicine, 030211 gastroenterology & hepatology, endoscopy, business, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2013
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11. Rare primary mitochondrial DNA mutations and probable synergistic variants in Leber's hereditary optic neuropathy

Author

Antoine Moulignier, Fabio Pizza, Dominique Bonneau, Pascal Reynier, Ghislaine Ducos, Alessandro Achilli, Maria Lucia Valentino, Sascha Fauser, Anna Maria De Negri, Patrizia Amati-Bonneau, Federico Sadun, Massimo Zeviani, Maria Pala, Christophe Orssaud, Beate Leo-Kottler, Rocco Liguori, Luisa Iommarini, Baharak Hooshiar Kashani, Bernd Wissinger, Valerio Carelli, Chiara La Morgia, Anna Olivieri, Piero Barboni, Hélène Dollfus, Vincent Procaccio, Antonio Torroni, Achilli A., Iommarini L., Olivieri A., Pala M., Hooshiar Kashani B., Reynier P., La Morgia C., Valentino M.L., Liguori R., Pizza F., Barboni P., Sadun F., De Negri A.M., Zeviani M., Dollfus H., Moulignier A., Ducos G., Orssaud C., Bonneau D., Procaccio V., Leo-Kottler B., Fauser S., Wissinger B., Amati-Bonneau P., Torroni A., Carelli V., Università degli Studi di Perugia (UNIPG), Università degli Studi di Bologna, Università di Pavia, Biologie Neurovasculaire et Mitochondriale Intégrée (BNMI), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université d'Angers (UA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), Les Hôpitaux Universitaires de Strasbourg (HUS), Fondation Ophtalmologique Adolphe de Rothschild [Paris], Clinique Saint-Jean Languedoc [Toulouse] (CSJL), Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), University Clinics Tuebingen [Germany], and University of Cologne

Subjects
Mitochondrial Diseases, [SDV]Life Sciences [q-bio], lcsh:Medicine, Q1, medicine.disease_cause, Mitochondrial/genetics, Haplogroup, Conserved sequence, polymorphism, 0302 clinical medicine, mtDNA, LHON, haplogroup, Leber/genetics, Genome Sequencing, lcsh:Science, Conserved Sequence, Phylogeny, Genetics, Leber, 0303 health sciences, Mutation, education.field_of_study, Multidisciplinary, Leber's hereditary optic neuropathy, Genomics, Mitochondrial, 3. Good health, Hereditary, Neurology, Medicine, Conserved Sequence/genetics, Polymorphism, Restriction Fragment Length, Research Article, Leber's Hereditary Optic Neuropathy, Mitochondrial DNA, congenital, hereditary, and neonatal diseases and abnormalities, Mutation/genetics, Amino Acid Sequence, Base Sequence, DNA, Mitochondrial, Family, Humans, Mitochondrial Proteins, Molecular Sequence Data, Optic Atrophy, Hereditary, Leber, Sequence Alignment, Species Specificity, Population, Biology, pathogenic mutation, rare mutations, Leber Hereditary Optic Neuropathy, 03 medical and health sciences, medicine, Mitochondrial Proteins/chemistry/genetics, education, QH426, Gene, 030304 developmental biology, Clinical Genetics, Point mutation, lcsh:R, nutritional and metabolic diseases, Genetic Variation, Human Genetics, DNA, medicine.disease, eye diseases, Optic Atrophy, Restriction Fragment Length, Genetics of Disease, Neuro-Ophthalmology, lcsh:Q, 030217 neurology & neurosurgery
Abstract

International audience; BACKGROUND: Leber's hereditary optic neuropathy (LHON) is a maternally inherited blinding disorder, which in over 90% of cases is due to one of three primary mitochondrial DNA (mtDNA) point mutations (m.11778G>A, m.3460G>A and m.14484T>C, respectively in MT-ND4, MT-ND1 and MT-ND6 genes). However, the spectrum of mtDNA mutations causing the remaining 10% of cases is only partially and often poorly defined. METHODOLOGY/PRINCIPAL FINDINGS: In order to improve such a list of pathological variants, we completely sequenced the mitochondrial genomes of suspected LHON patients from Italy, France and Germany, lacking the three primary common mutations. Phylogenetic and conservation analyses were performed. Sixteen mitochondrial genomes were found to harbor at least one of the following nine rare LHON pathogenic mutations in genes MT-ND1 (m.3700G>A/p.A132T, m.3733G>A-C/p.E143K-Q, m.4171C>A/p.L289M), MT-ND4L (m.10663T>C/p.V65A) and MT-ND6 (m.14459G>A/p.A72V, m.14495A>G/p.M64I, m.14482C>A/p.L60S, and m.14568C>T/p.G36S). Phylogenetic analyses revealed that these substitutions were due to independent events on different haplogroups, whereas interspecies comparisons showed that they affected conserved amino acid residues or domains in the ND subunit genes of complex I. CONCLUSIONS/SIGNIFICANCE: Our findings indicate that these nine substitutions are all primary LHON mutations. Therefore, despite their relative low frequency, they should be routinely tested for in all LHON patients lacking the three common mutations. Moreover, our sequence analysis confirms the major role of haplogroups J1c and J2b (over 35% in our probands versus 6% in the general population of Western Europe) and other putative synergistic mtDNA variants in LHON expression.

Published
2012
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12. Genotype-Phenotype Correlations in Charcot-Marie-Tooth Disease Type 2 Caused by Mitofusin 2 Mutations

Author

Marie-Christine Arne-Bes, Franck Sturtz, Corinne Magdelaine, Benoît Funalot, Brigitte Gilbert-Dussardier, Jean-Michel Vallat, Judith Calvo, Annick Toutain, Laurent Magy, Karima Ghorab, Marie-Christine Minot-Myhie, Claire Guillou, Jean-Pierre Carrière, Robert A. Ouvrier, Pierre Bouche, Philippe De Mas, Hubert Journel, Leila Lazaro, Service de Neurologie [CHU Limoges], CHU Limoges, Centre de référence national neuropathies périphériques rares [CHU Limoges], Intituto de neurologia, Universidad de la República [Montevideo] (UCUR), Biomolécules Thérapies anti-tumorales (EA4021), Université de Limoges (UNILIM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503), Service de Biochimie et Génétique Moléculaire [CHU Limoges], Institute of Neuromuscular Research, Westmead Hospital [Sydney], Département de médecine de l'enfant et de l'adolescent, Service de génétique [Tours], Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Consultation de génétique, Clinique Saint-Jean Languedoc [Toulouse] (CSJL), CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Service de Genetique medicale, Centre hospitalier universitaire de Poitiers (CHU Poitiers), Neurologie et Explorations Fonctionnelles du Système Nerveux [Toulouse], Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Hôpital de Rangueil, CHU Toulouse [Toulouse], Service de neurologie pédiatrique, Génétique Médicale, Centre hospitalier Bretagne Atlantique (Morbihan) (CHBA)-Hôpital Chubert, Service de rééducation fonctionnelle, and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau

Subjects
Male, Pathology, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease_cause, Severity of Illness Index, GTP Phosphohydrolases, 0302 clinical medicine, Charcot-Marie-Tooth Disease, Genotype, Missense mutation, Child, Genes, Dominant, 0303 health sciences, Mutation, education.field_of_study, Middle Aged, 3. Good health, Phenotype, Child, Preschool, Connexin 32, Female, [SDV.NEU]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC], Hereditary motor and sensory neuropathy, Adult, Genetic Markers, medicine.medical_specialty, Adolescent, Mutation, Missense, Genes, Recessive, Biology, Mitochondrial Proteins, 03 medical and health sciences, Young Adult, Arts and Humanities (miscellaneous), Molecular genetics, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, education, 030304 developmental biology, Aged, [SDV.GEN]Life Sciences [q-bio]/Genetics, Myelin protein zero, Membrane Proteins, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, medicine.disease, Peripheral neuropathy, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Neurology (clinical), 030217 neurology & neurosurgery
Abstract

International audience; Background: Mutations in the gene encoding mito- fusin 2 (MFN2) cause Charcot-Marie-Tooth disease type 2 (CMT2), with heterogeneity concerning severity and associated clinical features. Objective: To describe MFN2 mutations and associ- ated phenotypes in patients with hereditary motor and sensory neuropathy (HMSN). Design: Direct sequencing of the MFN2 gene and clini- cal investigations of patients with MFN2 mutations. Setting: Molecular genetics laboratory of a university hospital and the LimogesNational Referral Center for Rare Peripheral Neuropathies. Patients: One hundred fifty index patients with HMSN and amedianmotor nerve conduction velocity of 25m/s or greater and without mutations in the genes encoding connexin 32 and myelin protein zero. Main Outcome Measures: Results of genetic analy- ses and phenotypic observations. Results: Twenty different missense mutations were identified in 20 index patients. Mutation frequency was 19 of 107 (17.8%) in patients with CMT2 and 1 of 43 (2.3%) in patients with a median motor nerve conduc- tion velocity less than 38 m/s. Four patients had proven de novo mutations, 8 families had autosomal dominant inheritance, and 3 had autosomal recessive inheritance. The remaining 5 patients were sporadic cases with het- erozygous mutations. Phenotypes varied from mild forms to early-onset severe forms. Additional features were encountered in 8 patients (32%). Six patients un- derwent sural nerve biopsy: electronic microscopy showed prominent mitochondrial abnormalities on longitudinal sections. Conclusions: MFN2 mutations are a frequent cause of CMT2, with variable severity and either dominant or recessive inheritance. MFN2 gene testing must be a first-line analysis in axonal HMSN irrespective of the mode of inheritance or the severity of the peripheral neuropathy.

Published
2009

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