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1. A curriculum based certification of competence in gynaecologic surgical oncology

Author

Gwenael Ferron, Frederic Guyon, Pierre Collinet, Vincent Lavoué, Denis Querleu, Catherine Uzan, Cherif Akladios, François Golfier, Emile Daraï, Fabrice Lecuru, CHU Strasbourg, CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Curie [Paris], Hôpital Jeanne de Flandres, Université de Lille, Droit et Santé-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), CHU Pitié-Salpêtrière [AP-HP], CHU Pontchaillou [Rennes], CRLCC Eugène Marquis (CRLCC), Oncogenesis, Stress, Signaling (OSS), Université de Rennes (UR)-CRLCC Eugène Marquis (CRLCC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], UNICANCER, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Société européenne d’oncologie gynécologique

Subjects
Cancer gynécologique, Reproductive Medicine, Political science, Gynaecologic cancer, Compétence chirurgicale, Surgical skills, Obstetrics and Gynecology, Formation chirurgicale, [SDV.MHEP.GEO]Life Sciences [q-bio]/Human health and pathology/Gynecology and obstetrics, Humanities, Surgical training, Certification professionnelle
Abstract

International audience; Objective - In France, we are lacking an identified pathway for training in gynaecological cancer surgery. The four competent French learned societies, the SFOG, the CNGOF, the SFCO and the SCGP, supported by the CNU of Obstetrics &Gynaecology- and UNICANCER, agreed to materialize this course and attest it by a certification awarded by a national jury. Material and methods - The national committee of certification in gynaecological oncology made up of 10 members, representing the 6 concerned organizations, set itself 5 objectives: the definition of the eligibility criteria for training centres; the determination of a check-list to be filled by the candidate; the determination of a targeted curriculum for the training in gynecological oncological surgery; the determination of the assets necessary for the certification of a candidate already in practice; and the practical organization of the certification. Results - Criteria for approval of centres for training included 150 gynaecological cancer cases per year, among which 100 excisional surgeries, including 20 advanced-stage ovarian cancers. For certification of candidate who followed the curriculum established by the committee or by validation of prior experience for an actual practitioner, a candidate must validate a logbook and fill out a checklist including 4 parts: theoretical and practical training; research and publications; teaching and subscription to a continuing education program. The accomplished elements of the logbook and the checklist will be evaluated by a score. The first certification session is planned for the end of 2021. Conclusion - The optimisation of the surgical management of patients treated for gynaecological cancer is achieved through the identification of a training course and the certification, by a national jury, of the skills of surgeons who have completed it.

Published
2022
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2. PD-1 blockade restores helper activity of tumor-infiltrating, exhausted PD-1hiCD39+ CD4 T cells

Author

Victor Sarradin, Carine Valle, Frédéric Pont, Sébastien Vergez, Philippe Rochaix, Marie Michelas, Carlos Martínez-Gómez, Camille-Charlotte Balança, Marie Tosolini, Laurence Gladieff, Carlos Gomez-Roca, Jean-Pierre Delord, Christel Devaud, Agnès Dupret-Bories, Alejandra Martinez, Clara-Maria Scarlata, Gwenael Ferron, Eliane Mery, Anna Salvioni, Maha Ayyoub, Jean-Jacques Fournié, 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), Institut Claudius Regaud, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université Fédérale Toulouse Midi-Pyrénées, Fournié, jean-jacques, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Toulouse [Toulouse], CHU Toulouse [Toulouse]-Université Toulouse III - Paul Sabatier (UT3), and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Male, 0301 basic medicine, Lymphocyte, [SDV]Life Sciences [q-bio], Lymphocyte Cooperation, Programmed Cell Death 1 Receptor, Immunology, T cells, Gene Expression, Uterine Cervical Neoplasms, Cancer immunotherapy, CD8-Positive T-Lymphocytes, In Vitro Techniques, Biology, Lymphocyte Activation, 03 medical and health sciences, Lymphocytes, Tumor-Infiltrating, 0302 clinical medicine, Antigens, Neoplasm, Immune Tolerance, medicine, Humans, Cytotoxic T cell, RNA, Messenger, CD154, Ovarian Neoplasms, Immunity, Cellular, Apyrase, T-Lymphocytes, Helper-Inducer, General Medicine, Dendritic cell, Immune checkpoint, Tumor antigen, [SDV] Life Sciences [q-bio], 030104 developmental biology, medicine.anatomical_structure, Head and Neck Neoplasms, 030220 oncology & carcinogenesis, Cancer research, Medicine, Female, Tumor Escape, Cytokine secretion, CD8, Research Article
Abstract

International audience; Tumor antigen-specific CD4 T cells accumulate at tumor sites, evoking their involvement in antitumor effector functions in situ. Contrary to CD8 cytotoxic T lymphocyte exhaustion, that of CD4 T cells remains poorly appreciated. Here, using phenotypic, transcriptomic, and functional approaches, we characterized CD4 T cell exhaustion in patients with head and neck, cervical, and ovarian cancer. We identified a CD4 tumor-infiltrating lymphocyte (TIL) population, defined by high PD-1 and CD39 expression, which contained high proportions of cytokine-producing cells, although the quantity of cytokines produced by these cells was low, evoking an exhausted state. Terminal exhaustion of CD4 TILs was instated regardless of TIM-3 expression, suggesting divergence with CD8 T cell exhaustion. scRNA-Seq and further phenotypic analyses uncovered similarities with the CD8 T cell exhaustion program. In particular, PD-1hiCD39+ CD4 TILs expressed the exhaustion transcription factor TOX and the chemokine CXCL13 and were tumor antigen specific. In vitro, PD-1 blockade enhanced CD4 TIL activation, as evidenced by increased CD154 expression and cytokine secretion, leading to improved dendritic cell maturation and consequently higher tumor-specific CD8 T cell proliferation. Our data identify exhausted CD4 TILs as players in responsiveness to immune checkpoint blockade.

Published
2021
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3. A multivariate analysis of the prognostic impact of tumor burden, surgical timing and complexity after complete cytoreduction for advanced ovarian cancer

Author

Jaime Siegrist, Alejandra Martinez, Asunción Pérez-Benavente, Eliane Mery, Frédéric Guyon, Antonio Gil-Moreno, Gwenael Ferron, Alicia Hernández, Laurence Gladieff, Martina Aida Angeles, Bastien Cabarrou, Emanuela Spagnolo, Denis Querleu, Agnieszka Rychlik, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), CCSD, Accord Elsevier, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Claudius Regaud, Institut Bergonié [Bordeaux], UNICANCER, Hospital Universitario La Paz, and Universitat Autònoma de Barcelona (UAB)

Subjects
Adult, 0301 basic medicine, Oncology, medicine.medical_specialty, Multivariate analysis, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Carcinoma, Ovarian Epithelial, Interval debulking surgery, Neoadjuvant chemotherapy, Young Adult, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, Humans, Stage (cooking), Aged, Neoplasm Staging, Retrospective Studies, Aged, 80 and over, Ovarian Neoplasms, Primary debulking surgery, Chemotherapy, Advanced ovarian cancer, business.industry, food and beverages, Obstetrics and Gynecology, Cytoreduction Surgical Procedures, Middle Aged, Prognosis, Debulking, medicine.disease, Minimal residual disease, Neoadjuvant Therapy, Advanced epithelial ovarian cancer, Peritoneal cancer index, Tumor Burden, 3. Good health, [SDV] Life Sciences [q-bio], 030104 developmental biology, 030220 oncology & carcinogenesis, Multivariate Analysis, Ultraradical surgery, Peritoneal Cancer Index, Female, business, Ovarian cancer
Abstract

International audience; Objective: To assess the survival benefit of primary debulking surgery (PDS) compared to interval debulking surgery (IDS) after complete cytoreduction (CC-0) or cytoreduction to minimal residual disease (CC-1) in advanced ovarian cancer. Secondary objective was to evaluate the effect of tumor load and surgical complexity on patients' survival.Methods: A retrospective multicentric study was designed, including patients with IIIC-IV FIGO stage ovarian cancer who underwent PDS or IDS with CC-0 or CC-1 from January 2008 to December 2015 in four high-volume institutions. Patients were classified in three groups: PDS, IDS after 3-4 cycles of neoadjuvant chemotherapy (NACT), and IDS after 6 cycles. Disease-free survival (DFS) and overall survival (OS) were estimated. Univariable and multivariable analyses were conducted.Results: We included 549 patients, 175 (31.9%) underwent PDS, 224 (40.8%) had IDS after 3-4 cycles of NACT, and 150 (27.3%) underwent IDS after 6 cycles. Median DFS in PDS, IDS at 3-4 cycles and IDS at 6 cycles were 23.0 months (95%CI = [20.0-29.3]), 18.0 months (95%CI = [15.9-20.0]) and 17.1 months (95%CI = [15.0-20.9]), respectively; p < .001. Median OS were 84.0 months (95%CI = [68.3-111.0]), 50.7 months (95%CI = [44.6-59.5]) and 47.5 months (95%CI = [39.3-52.9]), respectively; p < .001. In multivariable analysis, high peritoneal cancer index score and NACT were negatively associated to DFS and OS. Surgical complexity and CC-1 were negatively associated to DFS.Conclusion: PDS offered a survival gain of almost three years compared to IDS in patients with minimal or no residual disease after surgery. PDS should remain the standard of care for advanced ovarian cancer.

Published
2020
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4. How should we stage and tailor treatment strategy in locally advanced cervical cancer? Imaging versus para-aortic surgical staging

Author

Martina Aida Angeles, Denis Querleu, Christophe Pomel, Gwenael Ferron, Alejandra Martinez, Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut Claudius Regaud, Unité de Biostatistiques [Toulouse] ( Institut Claudius Regaud / IUCT-O), Institut Claudius Regaud-Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Bergonié [Bordeaux], UNICANCER, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Imagerie Moléculaire et Stratégies Théranostiques (IMoST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Clermont Auvergne [2017-2020] (UCA [2017-2020]), 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), Institut Universitaire du Cancer Toulouse - Oncopôle (IUCT)-Institut Claudius Regaud, and Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
medicine.medical_specialty, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Locally advanced, Uterine Cervical Neoplasms, [SDV.CAN]Life Sciences [q-bio]/Cancer, Surgical staging, 03 medical and health sciences, 0302 clinical medicine, Medicine, Humans, Stage (cooking), Lymph node, ComputingMilieux_MISCELLANEOUS, Neoplasm Staging, Cervical cancer, 030219 obstetrics & reproductive medicine, business.industry, Obstetrics and Gynecology, Gold standard (test), medicine.disease, Survival Analysis, 3. Good health, Radiation therapy, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Female, Lymph, Radiology, Lymph Nodes, business
Abstract

Para-aortic lymph node status at initial assessment is the most important prognostic factor and a key point for the therapeutic strategy in patients with locally advanced cervical cancer. Undiagnosed lymph node metastasis is a major clinical problem as the finding of positive para-aortic lymph nodes leads to treatment modification, with a possible impact on disease free survival. When aortic lymph node disease is discovered, radiotherapy is extended to the para-aortic area, and other treatment modalities may be considered. Fluorine-18 fluorodeoxyglucose positron emission tomography/computed tomography (PET/CT) is the most accurate imaging examination to assess para-aortic extension in patients with locally advanced cervical cancer. The gold standard to identify para-aortic extension remains histologic evaluation of the lymph nodes. Indeed, PET/CT fails to detect approximately 10–15% of patients with negative PET/CT aortic nodes who have lymph node metastasis on pathologic staging. Patients with positive pelvic lymph nodes have para-aortic extension in 25–30% of cases, and surgical staging will lead to treatment modification and probably to improved para-aortic and distant control. Surgical staging also avoids unnecessary toxicity associated with extended field radiation in approximately 75% of patients with pelvic lymph node metastasis. The best modality to identify para-aortic extension is histological evaluation of the lymph nodes, but the survival benefit of surgical staging remains controversial. On the other hand, current studies include a majority of patients without pelvic lymph node spread, who are likely to be those who will benefit the least from surgical staging.

Published
2020
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5. Dual Relief of T-lymphocyte Proliferation and Effector Function Underlies Response to PD-1 Blockade in Epithelial Malignancies

Author

Alejandra Martinez, Camille-Charlotte Balança, Jean-Jacques Fournié, Carlos Martinez Gomez, Laurence Gladieff, Philippe Rochaix, Jérôme Sarini, Maha Ayyoub, Carlos Gomez-Roca, Carine Valle, Agnès Dupret-Bories, Christel Devaud, Victor Sarradin, Benjamin Vairel, Virginie Feliu, Aurore Siegfried-Vergnon, Jean-Pierre Delord, Camille Franchet, Yann Tanguy Le Gac, Lucile Mir-Mesnier, Diana Heaugwane, Clara-Maria Scarlata, Frédéric Pont, Stéphanie Motton, Marie Michelas, Eliane Mery, Françoise Lauzeral-Vizcaino, Sébastien Vergez, Marie Tosolini, Claire Illac, Gwenael Ferron, 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), 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), CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées, Centre National de la Recherche Scientifique - CNRS (FRANCE), Institut National de la Santé et de la Recherche Médicale - INSERM (FRANCE), Université Toulouse III - Paul Sabatier - UT3 (FRANCE), Institut Claudius Regaud - ICR (FRANCE), Centre Hospitalier Universitaire de Toulouse - CHU Toulouse (FRANCE), Institut Universitaire du Cancer de Toulouse - Oncopole - IUCT (Toulouse, France), (OATAO), Open Archive Toulouse Archive Ouverte, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Cancer Research, [SDV]Life Sciences [q-bio], Immunology, Population, Programmed Cell Death 1 Receptor, [SDV.CAN]Life Sciences [q-bio]/Cancer, CD8-Positive T-Lymphocytes, Lymphocyte Activation, [SDV.IMM.II]Life Sciences [q-bio]/Immunology/Innate immunity, 03 medical and health sciences, Mice, 0302 clinical medicine, Immune system, Antineoplastic Agents, Immunological, CD28 Antigens, [SDV.CAN] Life Sciences [q-bio]/Cancer, Bystander effect, Medicine, Animals, Humans, Neoplasms, Glandular and Epithelial, education, Receptor, [SDV.IMM.II] Life Sciences [q-bio]/Immunology/Innate immunity, Cell Proliferation, Cancer, education.field_of_study, Lymphocytes T, business.industry, CD28, Immune checkpoint, 3. Good health, Blockade, Mice, Inbred C57BL, Survival Rate, 030104 developmental biology, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, 030220 oncology & carcinogenesis, [SDV.IMM.IA] Life Sciences [q-bio]/Immunology/Adaptive immunology, Cancer research, Female, Single-Cell Analysis, business, Transcriptome, CD8
Abstract

Although understanding of T-cell exhaustion is widely based on mouse models, its analysis in patients with cancer could provide clues indicating tumor sensitivity to immune checkpoint blockade (ICB). Data suggest a role for costimulatory pathways, particularly CD28, in exhausted T-cell responsiveness to PD-1/PD-L1 blockade. Here, we used single-cell transcriptomic, phenotypic, and functional approaches to dissect the relation between CD8+ T-cell exhaustion, CD28 costimulation, and tumor specificity in head and neck, cervical, and ovarian cancers. We found that memory tumor–specific CD8+ T cells, but not bystander cells, sequentially express immune checkpoints once they infiltrate tumors, leading, in situ, to a functionally exhausted population. Exhausted T cells were nonetheless endowed with effector and tumor residency potential but exhibited loss of the costimulatory receptor CD28 in comparison with their circulating memory counterparts. Accordingly, PD-1 inhibition improved proliferation of circulating tumor–specific CD8+ T cells and reversed functional exhaustion of specific T cells at tumor sites. In agreement with their tumor specificity, high infiltration of tumors by exhausted cells was predictive of response to therapy and survival in ICB-treated patients with head and neck cancer. Our results showed that PD-1 blockade–mediated proliferation/reinvigoration of circulating memory T cells and local reversion of exhaustion occur concurrently to control tumors.

Published
2020
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6. Recommandations de la Société française de chirurgie oncologique (SFCO) pour l’organisation de la chirurgie oncologique durant l’épidémie de COVID-19

Author

Fabrice Lecuru, Jean-Marc Classe, Gilles Dolivet, Léa Leufflen, Gwenael Ferron, Serge Evrard, Michel Rivoire, Olivia Sgarbura, Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institut Bergonié [Bordeaux], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Curie [Paris], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), Centre Léon Bérard [Lyon], 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), Maquin, Didier, and Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, Cancer Research, medicine.medical_specialty, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), [SDV.CAN]Life Sciences [q-bio]/Cancer, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Medicine, Radiology, Nuclear Medicine and imaging, Gynecology, biology, business.industry, Hematology, General Medicine, Neoplasms surgery, Surgical procedures, biology.organism_classification, 3. Good health, 030104 developmental biology, Oncology, Radiology Nuclear Medicine and imaging, 030220 oncology & carcinogenesis, business, Betacoronavirus
Abstract

International audience; PréambuleLa pandémie de COVID 19 impacte l’activité de chirurgie oncologique, directement et indirectement. Les patients atteints de cancer sont plus à risque d’infection du fait de l’immunosuppression secondaire au cancer et aux traitements (chimiothérapie, chirurgie). En cas d’infection COVID 19, les patients atteints de cancer ont plus de risque d’évolution péjorative que les patients indemnes de cancer [1]. Il faut donc à tout prix éviter l’infection COVID 19 pour les patients atteints de cancer.

Published
2020
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7. Development of a near infrared protein nanoprobe targeting Thomsen-Friedenreich antigen for intraoperative detection of submillimeter nodules in an ovarian peritoneal carcinomatosis mouse model

Author

Muriel Golzio, Elisabeth Bellard, Sophie Chabot, Mathilde Coustets, Mélissa Prat, Marie-Pierre Rols, Laurent Paquereau, Gwenael Ferron, Vincent Ecochard, Caroline Ladurantie, Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Institut Claudius Regaud, Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Centre de Physiopathologie Toulouse Purpan (CPTP), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), and Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)

Subjects
[SDV.BIO]Life Sciences [q-bio]/Biotechnology, [SDV.IB.IMA]Life Sciences [q-bio]/Bioengineering/Imaging, Biophysics, Nanoprobe, Bioengineering, [SDV.CAN]Life Sciences [q-bio]/Cancer, 02 engineering and technology, Ovarian peritoneal carcinomatosis, Biomaterials, 03 medical and health sciences, Peritoneal cavity, Mice, Antigen, In vivo, Thomsen-friedenreich antigen, Carcinoma, medicine, Tumor Microenvironment, Protein nanoprobe, Animals, Humans, Antigens, Tumor-Associated, Carbohydrate, Peritoneal Neoplasms, 030304 developmental biology, Ovarian Neoplasms, 0303 health sciences, Tumor microenvironment, Thomsen-Friedenreich Antigen, business.industry, Nanocontainer, 021001 nanoscience & nanotechnology, medicine.disease, 3. Good health, Near infrared fluorescence, medicine.anatomical_structure, Mechanics of Materials, Ceramics and Composites, Cancer research, Cancer imaging, Female, Neoplasm Recurrence, Local, 0210 nano-technology, business
Abstract

International audience; The epithelial ovarian cancer is one of the most lethal gynecological malignancy due to its late diagnostic and many relapses observed after first line of treatment. Once diagnose, the most important prognostic factor is the completeness of cytoreductive surgery. To achieve this goal, surgeons have to pinpoint and remove nodules, especially the smallest nodules. Recent advances in fluorescence-guided surgery led us to develop a recombinant lectin as a nanoprobe for the microscopic detection of nodules in the peritoneal cavity of tumor-bearing mice. This lectin has an intrinsic specificity for a carcinoma-associated glycan biomarker, the Thomsen-Friedenreich antigen. In this study, after its labelling by a near infrared dye, we first demonstrated that this nanoprobe allowed indirect detection of nodules already implanted in the peritoneal cavity, through tumor microenvironment targeting. Secondly, in a protocol mimicking the scattering of cells during surgery, we obtained a direct and long-lasting detection of tumor cells in vivo. This lectin as already been described as a nanocontainer able to do targeted delivery of a therapeutic compound to carcinoma cells. Future developments will focus on the combination of the nanoprobe and nanocontainer aspects in an intraperitoneal nanotheranostic approach.

Published
2020
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8. Tumor cells educate mesenchymal stromal cells to release chemoprotective and immunomodulatory factors

Author

Alejandra Martinez, Renaud Mével, Jean-Pierre Delord, Lise Lefèvre, Muriel Golzio, Eliane Mery, Marie-Véronique Joubert, Kimberley Coulson, Agnès Coste, Gwenael Ferron, Mélissa Prat, Hélène Leray, Benoît Thibault, Léa Lemaitre, Bettina Couderc, Augustin Le Naour, 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), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Institut de pharmacologie et de biologie structurale (IPBS), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Infections Parasitaires : Transmission, Physiopathologie et Thérapeutiques (IP-TPT), Service de Santé des Armées-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU)-Institut de Recherche pour le Développement (IRD), Institut Claudius Regaud. Department of pathology, Group of Intelligent and Cooperative Systems / Education,Media, Informatics and Culture (GSIC/EMIC), Universidad de Valladolid [Valladolid] (UVa), Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Faculté des Sciences Pharmaceutiques, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), 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), Pharmacochimie et Biologie pour le Développement (PHARMA-DEV), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie de Toulouse (ICT-FR 2599), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Institut de Chimie du CNRS (INC)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Institut de Chimie du CNRS (INC)-Institut de Recherche pour le Développement (IRD), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Recherche pour le Développement (IRD)-Institut de Chimie de Toulouse (ICT), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Institut National Polytechnique (Toulouse) (Toulouse INP), Université de Toulouse (UT)-Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT), and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS)

Subjects
ovarian adenocarcinoma, Chemokine, Biopsy, chemokines, Cell Communication, Mice, Ovarian tumor, 0302 clinical medicine, Neoplasms, Tumor Microenvironment, CXC chemokine receptors, ComputingMilieux_MISCELLANEOUS, Ovarian Neoplasms, 0303 health sciences, biology, Chemistry, chemoresistance, Cell Differentiation, General Medicine, 3. Good health, CXCL2, 030220 oncology & carcinogenesis, Cytokines, Female, mesenchymal stromal cells, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Models, Biological, Article, Immunomodulation, 03 medical and health sciences, Cell Line, Tumor, Genetics, Animals, Humans, Immunologic Factors, Interleukin 8, Molecular Biology, 030304 developmental biology, Receptors, CXCR, Gene Expression Profiling, Macrophages, Mesenchymal stem cell, Computational Biology, Mesenchymal Stem Cells, Cell Biology, Editor's Choice, Disease Models, Animal, Drug Resistance, Neoplasm, Tumor progression, Cancer cell, biology.protein, Cancer research, Biomarkers
Abstract

Factors released by surrounding cells such as cancer-associated mesenchymal stromal cells (CA-MSCs) are involved in tumor progression and chemoresistance. In this study, we characterize the mechanisms by which naïve mesenchymal stromal cells (MSCs) can acquire a CA-MSCs phenotype. Ovarian tumor cells trigger the transformation of MSCs to CA-MSCs by expressing pro-tumoral genes implicated in the chemoresistance of cancer cells, resulting in the secretion of high levels of CXC chemokine receptors 1 and 2 (CXCR1/2) ligands such as chemokine (C-X-C motif) ligand 1 (CXCL1), CXCL2, and interleukin 8 (IL-8). CXCR1/2 ligands can also inhibit the immune response against ovarian tumor cells. Indeed, through their released factors, CA-MSCs promote the differentiation of monocytes towards M2 macrophages, which favors tumor progression. When CXCR1/2 receptors are inhibited, these CA-MSC-activated macrophages lose their M2 properties and acquire an anti-tumoral phenotype. Both ex vivo and in vivo, we used a CXCR1/2 inhibitor to sensitize ovarian tumor cells to carboplatin and circumvent the pro-tumoral effects of CA-MSCs. Since high concentrations of CXCR1/2 ligands in patients’ blood are associated with chemoresistance, CXCR1/2 inhibition could be a potential therapeutic strategy to revert carboplatin resistance.

Published
2019
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9. Quelle prise en charge optimale pour un sarcome du cordon spermatique en 2018 ?

Author

P. Meeus, François Quenet, R. Tetreau, C. Llacer, J.-B. Delhorme, M. Fau, Dimitri Tzanis, Eberhard Stoeckle, Gsf-Geto, N. Firmin, Charles Honoré, Gauthier Decanter, S. Carrere, B. Meunier, D. Cupissol, S. Bonvalot, Gwenael Ferron, CCSD, Accord Elsevier, Institut du Cancer de Montpellier (ICM), Institut Gustave Roussy (IGR), Institut Curie [Paris], Hôpital de Hautepierre [Strasbourg], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER, 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), Institut Bergonié [Bordeaux], Centre Léon Bérard [Lyon], Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Pontchaillou [Rennes], and Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Gynecology, medicine.medical_specialty, Soft tissue sarcoma, Pluridisciplinarité, business.industry, Urology, [SDV]Life Sciences [q-bio], 030232 urology & nephrology, Quality, Sarcome du cordon spermatique, 3. Good health, [SDV] Life Sciences [q-bio], 03 medical and health sciences, Sarcome des tissus mous, 0302 clinical medicine, Mulidisciplinarity, Medicine, Surgery, business, Chirurgie, Spermatic cord sarcoma, Qualité
Abstract

Spermatic cord sarcomas are rare tumors for which the most important is the initial diagnostic procedure. They are frequently misdiagnosed after surgery for inguinal hernia, inguinal lymphadenectomy or testicular malignancy. Any clinical suspicion has to lead to perform imaging with MRI and a core needle biopsy in order to obtain an accurate preoperative diagnosis. Liposarcoma and leiomyosarcoma are the most common histological subtypes in elderly adults, rhabdomyosarcoma in children or in young adults. A CT scan will precede the treatment in order to look for distant metastasis and abdominal involvement. The therapeutic strategy as well as the surgical planning are then adapted to the histological, morphological and prognostic factors. Surgery is the cornerstone for the treatment of spermatic cord sarcoma. The minimum requirements for the surgical procedure are a wide excision of the tumor en bloc with radical orchidectomy, excision of the ipsilateral scrotum and high spermatic cord ligation. It could be enlarged to the anterior abdominal wall and adjacent organs some required a soft tissue flap. Spermatic cord sarcoma and trunk wall sarcoma have the same prognosis for which local recurrence could significantly decrease survival. Consequently, surgeon in charge with these tumors has to be familiar with soft tissue sarcoma and the management of these patients must be carried out under the supervision of a multidisciplinary team within the Netsarc network., Le sarcome du cordon spermatique est une pathologie rare pour laquelle la prise en charge initiale est d’importance primordiale. Le diagnostic est souvent découvert a posteriori après une chirurgie pour cure de hernie inguinale, pour suspicion de cancer du testicule ou après exérèse d’une adénopathie inguinale. Toute suspicion clinique doit donc faire l’objet d’une imagerie par résonance magnétique (IRM) et d’une biopsie percutanée sous contrôle radiologique dans le but d’obtenir un diagnostic préopératoire précis. Les histologies les plus fréquentes sont le liposarcome et le léiomyosarcome chez l’adulte âgé, le rhabdomyosarcome chez l’enfant et l’adulte jeune. Un bilan d’extension intra-abdominal et à distance par scanner précédera le traitement. La stratégie thérapeutique de même que la planification chirurgicale sont ensuite adaptées aux paramètres histologiques, morphologiques et pronostiques. La chirurgie est la pierre angulaire du traitement des sarcomes du cordon spermatique. Le geste minimal requis est l’exérèse de la tumeur en bloc avec la réalisation d’une orchidectomie totale, l’exérèse du cordon spermatique et la ligature des vaisseaux spermatiques à l’orifice inguinal profond. Elle peut être élargie à la paroi abdominale et aux organes de voisinage et nécessiter si besoin une reconstruction par lambeau. Le pronostic des sarcomes du cordon spermatique est équivalent à celui des sarcomes du tronc dont l’évolutivité locale est péjorative pour la survie des patients. De fait, l’exérèse doit être réalisée par un chirurgien ayant l’expertise des problématiques liées à la chirurgie des sarcomes au sein d’un centre spécialisé du réseau Netsarc.

Published
2019
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10. Fluorescence-guided surgery for cancer patients: a proof of concept study on human xenografts in mice and spontaneous tumors in pets

Author

Muriel Golzio, Didier Lanore, Denis Querleu, Stephanie Guillermet, Anne Françoise Tilkin-Mariamé, Gwenael Ferron, Eliane Mery, Bettina Couderc, E. Bellard, Jean Pierre Delord, Augustin Le Naour, Benoît Thibault, Institut Claudius Regaud. Department of pathology, Institut de pharmacologie et de biologie structurale (IPBS), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Laboratoire d'Imagerie Moléculaire Expérimentale (LIME), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Institut de Recherche en Santé Digestive (IRSD ), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Pharmacologie Clinique et Expérimentale des Médicaments Anticancéreux, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut Claudius Regaud, Department of Surgical Oncology, Institut Claudius Regaud, CRLCC Institut Claudius Regaud, Faculté des Sciences Pharmaceutiques, Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Golzio, Muriel, Fluoptics Europe [Grenoble] (Minatec-BHT), Clinique Vétérinaire Alliance [Bordeaux] (CVA), and Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3)

Subjects
0301 basic medicine, Tumor targeting, Pathology, medicine.medical_specialty, [SDV.MHEP.CHI] Life Sciences [q-bio]/Human health and pathology/Surgery, Angiogenesis, [SDV.CAN]Life Sciences [q-bio]/Cancer, [SDV.MHEP.CHI]Life Sciences [q-bio]/Human health and pathology/Surgery, 03 medical and health sciences, Peritoneal cavity, optical imaging, 0302 clinical medicine, Optical imaging, [SDV.CAN] Life Sciences [q-bio]/Cancer, medicine, spontaneous animal models, ComputingMilieux_MISCELLANEOUS, business.industry, tumor targeting, Cancer, medicine.disease, 3. Good health, Peritoneal carcinomatosis, Surgery, Clinical trial, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Fluorescent staining, integrins, business, fluorescence-guided surgery, Research Paper
Abstract

// Eliane Mery 1, * , Muriel Golzio 2, * , Stephanie Guillermet 3 , Didier Lanore 4 , Augustin Le Naour 1 , Benoit Thibault 1 , Anne Francoise Tilkin-Mariame 1 , Elizabeth Bellard 2 , Jean Pierre Delord 1 , Denis Querleu 1 , Gwenael Ferron 1, * and Bettina Couderc 1, * 1 Institut Claudius Regaud –IUCT Oncopole, University Toulouse III, Toulouse, France 2 Institut de Pharmacologie et de Biologie Structurale, Universite de Toulouse, Toulouse, France 3 Fluoptics SAS, Grenoble, France 4 Clinique veterinaire Alliance, Bordeaux, France * These authors have contributed equally to this work Correspondence to: Bettina Couderc, email: Couderc.bettina@iuct-oncopole.fr Keywords: tumor targeting; optical imaging; fluorescence-guided surgery; integrins; spontaneous animal models Received: July 27, 2017 Accepted: October 28, 2017 Published: November 30, 2017 ABSTRACT Surgery is often the first treatment option for patients with cancer. Patient survival essentially depends on the completeness of tumor resection. This is a major challenge, particularly in cases of peritoneal carcinomatosis, where tumors are widely disseminated in the large peritoneal cavity. Any development to help surgeons visualize these residual cells would improve the completeness of the surgery. For non-disseminated tumors, imaging could be used to ensure that the tumor margins and the draining lymph nodes are free of tumor deposits. Near-infrared fluorescence imaging has been shown to be one of the most convenient imaging modalities. Our aim was to evaluate the efficacy of a near-infrared fluorescent probe targeting the αvβ3 integrins (Angiostamp™) for intraoperative detection of tumors using the Fluobeam® device. We determined whether different human tumor nodules from various origins could be detected in xenograft mouse models using both cancer cell lines and patient-derived tumor cells. We found that xenografts could be imaged by fluorescent staining irrespective of their integrin expression levels. This suggests imaging of the associated angiogenesis of the tumor and a broader potential utilization of Angiostamp™. We therefore performed a veterinary clinical trial in cats and dogs with local tumors or with spontaneous disseminated peritoneal carcinomatosis. Our results demonstrate that the probe can specifically visualize both breast and ovarian nodules, and suggest that Angiostamp™ is a powerful fluorescent contrast agent that could be used in both human and veterinary clinical trials for intraoperative detection of tumors.

Published
2017
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11. Peritoneal carcinomatosis treated with cytoreductive surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for advanced ovarian carcinoma: A French multicentre retrospective cohort study of 566 patients

Author

Evelyne Decullier, Christophe Pomel, François Quenet, Jean-Marc Classe, Jack Porcheron, Olivier Glehen, Marc Pocard, Naoual Bakrin, Frédéric Guyon, Pierre Meeus, J.M. Bereder, Sebastien Gouy, Karine Abboud, Gwenael Ferron, Simon Msika, Gérard Lorimier, Philippe Morice, Frédéric Marchal, Department of Obstetrics and Gynaecology, Hospices Civils de Lyon (HCL), Ciblage thérapeutique en Oncologie (EA3738), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Centre Hospitalier L'archet II, Santé Individu Société - SIS (SIS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université Lumière - Lyon 2 (UL2), Institut de Cancérologie de l'Ouest [Angers/Nantes] (UNICANCER/ICO), UNICANCER, Hôpital Louis Mourier - AP-HP [Colombes], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de chirurgie digestive, CHU Louis Mourrier, Centre Paul Papin, CRLCC Paul Papin, Hôpital Nord, Hôpital nord, Service d'Oncologie Chirurgicale, Centre Léon Bérard [Lyon], Department of Surgical Oncology Institut Claudius Regaud, Institut Claudius Regaud, Center Val d'Aurel, UNICANCER - Institut régional du Cancer Montpellier Val d'Aurelle (ICM), CRLCC Val d'Aurelle - Paul Lamarque, Département de chirurgie, Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER-UNICANCER, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Centre Alexis Vautrin (CAV), Département de chirurgie générale [Gustave Roussy], Institut Gustave Roussy (IGR), Department of Surgical Oncology, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), Hôpital Lariboisière, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Lariboisière-Fernand-Widal [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Carcinose Angiogenèse et Recherche Translationnelle, Angiogenese et recherche translationnelle (CART U965), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Molécules Thérapeutiques in silico (MTI), Plateforme de génétique moléculaire des cancers d'Aquitaine, Institut Bergonié [Bordeaux], Department of Oncologic Surgery, Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Institut de cancérologie de l'Ouest - Nantes (ICO Nantes), CRLCC Paul Papin-CRLCC René Gauducheau, Hopital Louis Mourier - AP-HP [Colombes], CRLCC Institut Claudius Regaud, UNICANCER - Institut régional du Cancer [Montpellier] (ICM), Institut de Cancérologie de Lorraine - Alexis Vautrin (ICL), Jean Perrin Comprehensive Cancer Centre, Centre Jean Perrin, CRLCC Jean Perrin, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Lariboisière-Université Paris Diderot - Paris 7 (UPD7), Institut Bergonié - CRLCC Bordeaux, Santé Individu Société (SIS), Université Lumière - Lyon 2 (UL2)-Université Jean Moulin - Lyon 3 (UJML), Université de Lyon-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Hospices Civils de Lyon (HCL)-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire de Saint-Etienne [CHU Saint-Etienne] (CHU ST-E), Département de chirurgie [ICL Alexis Vautrin], and Université de Lyon-Hospices Civils de Lyon (HCL)-Université Jean Monnet [Saint-Étienne] (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
Kaplan-Meier Estimate, Disease, 0302 clinical medicine, Ovarian carcinoma, Medicine, Renal Insufficiency, Peritoneal Neoplasms, Ovarian Neoplasms, Response rate (survey), peritoneal carcinomatosis, Digestive System Fistula, General Medicine, Middle Aged, hyperthermia, 3. Good health, Survival Rate, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, ovarian cancer, Oncology, 030220 oncology & carcinogenesis, Female, 030211 gastroenterology & hepatology, Hyperthermic intraperitoneal chemotherapy, France, Adult, medicine.medical_specialty, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Postoperative Hemorrhage, intraperitoneal chemotherapy, Disease-Free Survival, 03 medical and health sciences, Humans, Aged, Proportional Hazards Models, Retrospective Studies, HIPEC, business.industry, Carcinoma, Retrospective cohort study, Hyperthermia, Induced, Leukopenia, medicine.disease, Surgery, Chemotherapy, Cancer, Regional Perfusion, Conventional PCI, Peritoneal Cancer Index, business, Ovarian cancer
Abstract

International audience; BACKGROUND: Despite a high response rate to front-line therapy, prognosis of epithelial ovarian carcinoma (EOC) remains poor. Approaches that combine Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with this strategy. PATIENTS AND METHODS: A retrospective cohort multicentric study from French centres was performed. All consecutive patients with advanced and recurrent EOC treated with CRS and HIPEC were included. RESULTS: The study included 566 patients from 13 centres who underwent 607 procedures between 1991 and 2010. There were 92 patients with advanced EOC (first-line treatment), and 474 patients with recurrent EOC. A complete cytoreductive surgery was performed in 74.9% of patients. Mortality and grades 3 to 4 morbidity rates were 0.8% and 31.3%, respectively. The median overall survivals were 35.4 months and 45.7 months for advanced and recurrent EOC, respectively. There was no significant difference in overall survival between patients with chemosensitive and with chemoresistant recurrence. Peritoneal Cancer Index (PCI) that evaluated disease extent was the strongest independent prognostic factor for overall and disease-free survival in all groups. CONCLUSION: For advanced and recurrent EOC, curative therapeutic approach combining optimal CRS and HIPEC should be considered as it may achieve long-term survival in patients with a severe prognosis disease, even in patients with chemoresistant disease. PCI should be used for patient's selection.

Published
2013
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12. Exentération pelvienne : actualités et perspectives

Author

Frédéric Marchal, Eric Lambaudie, Christophe Pomel, Denis Querleu, Gwenael Ferron, Philippe Rouanet, Alejandra Martinez, Fabrice Narducci, Institut Claudius Regaud, Centre Jean Perrin [Clermont-Ferrand] (UNICANCER/CJP), UNICANCER, Group of Intelligent and Cooperative Systems / Education,Media, Informatics and Culture (GSIC/EMIC), Universidad de Valladolid [Valladolid] (UVa), Department of Surgical Oncology Centre Oscar Lambret, Department of Surgery, Centre Régional de Lutte contre le Cancer Oscar Lambret [Lille] (UNICANCER/Lille), Université de Lille-UNICANCER-Université de Lille-UNICANCER, Département de chirurgie Paoli Calmette (Paoli Calmette), Centre Alexis Vautrin (CAV), Centre de Recherche en Automatique de Nancy (CRAN), Université Henri Poincaré - Nancy 1 (UHP)-Institut National Polytechnique de Lorraine (INPL)-Centre National de la Recherche Scientifique (CNRS), Department of Surgical Oncology, Centre Val d'Aurelle, and Université Lille Nord de France (COMUE)-UNICANCER-Université Lille Nord de France (COMUE)-UNICANCER

Subjects
Gynecology, medicine.medical_specialty, 030219 obstetrics & reproductive medicine, Poche de Miami, Pelvic exenteration, Vaginal reconstruction, business.industry, Exentération pelvienne, medicine.medical_treatment, Treatment outcome, Obstetrics and Gynecology, General Medicine, Radiothérapie peropératoire, 3. Good health, [SDV.BBM.BP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biophysics, 03 medical and health sciences, Reconstruction vaginale, 0302 clinical medicine, Reproductive Medicine, Pelvis surgery, 030220 oncology & carcinogenesis, medicine, Dérivation urinaire continente, business, Intraoperative radiotherapy
Abstract

National audience; Les indications d'exentération pelvienne ont fortement diminué compte tenu de l'amélioration du contrôle local des tumeurs localement avancées depuis l'avènement de la radiochimiothérapie. Un bilan exhaustif par une imagerie moderne permet de planifier correctement le type d'exérèse nécessaire. L'utilisation de nouveaux moyens d'hémostase permet de réduire les saignements peropératoires. L'extension latéro-pelvienne doit faire discuter une prise en charge spécifique avec une résection de la paroi pelvienne latérale et de ses éléments vasculo-nerveux et/ou l'association à des techniques de radiothérapie peropératoire. Pour les tumeurs centro-pelviennes, l'abord cœlioscopique peut représenter une option. Le temps de reconstruction est primordial : le comblement pelvien permet de réduire le taux de complication postopératoire. Les dérivations urinaires continentes représentent une technique de choix pour des patientes jeunes et motivées. La reconstruction vaginale en particulier par lambeau musculo-cutané doit être systématiquement proposée afin rétablir le schéma corporel et de participer au comblement pelvien. Le développement de la technique de perfusion isolée de pelvis représentera certainement une alternative à l'exentération pelvienne ou une thérapeutique néo-adjuvante afin d'améliorer les résultats carcinologiques

Published
2012
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13. Morbidity of diaphragmatic surgery for advanced ovarian cancer: Retrospective study of 148 cases

Author

Christophe Pomel, Fabrice Lecuru, Emile Daraï, Fabrice Narducci, Roman Rouzier, Elisabeth Chereau, Eric Leblanc, C. Bergzoll, Sebastien Gouy, Denis Querleu, Gwenael Ferron, Cyrille Huchon, P. Morice, CHU Tenon [AP-HP], Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de chirurgie générale [Gustave Roussy], Institut Gustave Roussy (IGR), Department of Surgical Oncology Institut Claudius Regaud, Department of Surgical Oncology Centre Oscar Lambret, Department of Surgical Oncology Centre Jean Perrin, and Department of Gynecologic and Oncologic Surgery Hopital Européen Georges Pompidou

Subjects
Adult, medicine.medical_specialty, Adolescent, Pleural effusion, Fistula, Diaphragm, Diaphragmatic breathing, morbidity, survival, complete surgery, 03 medical and health sciences, 0302 clinical medicine, medicine, Humans, Radical surgery, Aged, Retrospective Studies, Aged, 80 and over, Ovarian Neoplasms, 030219 obstetrics & reproductive medicine, business.industry, General surgery, Pulmonary Complication, Retrospective cohort study, General Medicine, Middle Aged, medicine.disease, 3. Good health, Pulmonary embolism, Surgery, Treatment Outcome, ovarian cancer, Oncology, Pneumothorax, 030220 oncology & carcinogenesis, Female, business, diaphragmatic surgery
Abstract

Background Treatment of Advanced Ovarian Cancer (AOC) includes surgery with complete cytoreduction, one of the strongest prognostic factors. To achieve complete cytoreduction, diaphragmatic surgery is often required. There is currently a lack of information in the literature regarding the morbidity and impact of this type of surgery. The aim of this study is to report specific pulmonary morbidity and overall morbidity associated with diaphragmatic surgery in patients with AOC. Materials and methods We conducted a multicentric (6 centres), retrospective study that included 148 patients operated on between 2004 and 2008. Patient characteristics, surgical course and postoperative complications were collected. Results The complete cytoreduction rate was 84%. The surgery was categorised by timing as initial, interval or recurrence surgery in 38%, 51% and 11% of patients, respectively. In 69% of patients, one or more postoperative complications occurred: pulmonary complication (42%), digestive fistula (7%) or lymphocyst (18%). The pulmonary complications were pleural effusion (37%), pulmonary embolism (5%), pneumothorax (4%) and pulmonary infection (2%). These complications required revision surgery, pleural evacuation, or lymphocyst evacuation in 13%, 14%, and 11% of the cases, respectively. Postoperative mortality was 3%. Risk factors for pulmonary complications were the addition of extensive upper surgery to the diaphragmatic surgery ( p = 0.014) and the size of the diaphragmatic resection ( p = 0.012). Conclusions Diaphragmatic surgery achieved complete removal of the tumour but resulted in pulmonary complications in addition to complications of radical surgery.

Published
2011
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