Serge EVRARD est Professeur de Cancérologie (option chirurgie – classe exceptionnelle) à l’Université de Bordeaux. A l’Institut, il coordonne le Département de Chirurgie.
Après des études de médecine à Nancy (1978-1984), Serge Evrard obtient à Strasbourg son doctorat en médecine et son diplôme spécialisé en chirurgie viscérale (1985-1990). Lauréat de la Faculté, il obtient son doctorat en sciences de l’Université Paris VII et son Habilitation à Diriger les Recherches en 1993. Il est nommé Professeur des Universités-Praticien Hospitalier en 1994. En 1999, il rejoint l’Institut Bergonié pour compléter et développer le Groupe Digestif. A l’échelon national, il a présidé la Société Française du Cancer ainsi que la Société Française de Chirurgie Oncologique qu’il a cofondée en 2007. A l’échelon international, il est membre du bureau exécutif de la société européenne de chirurgie oncologique, The European Society of Surgical Oncology, dont il dirige également la recherche clinique. En 2014, il a créé la plateforme de recherche en chirurgie oncologique SURCARE, une collaboration entre l’ESSO et l’EORTC (European Organisation for Research and Treatment of Cancer) dont il est également membre du comité exécutif. Serge Evrard est expert auprès de l’INCA et du HCERES. Il est membre du groupe de recherche biologique de Majid Khatib (INSERM).
Pour contacter Serge Evrard :
- Chirurgie : am.chir-anesth@bordeaux.unicancer.fr
- Digestif : am.dig@bordeaux.unicancer.fr
Le Professeur Evrard est spécialisé dans la prise en charge des tumeurs digestives: estomac, intestin grêle, colon, rectum, anus, foie, pancréas et péritoine, à l’exclusion des tumeurs eosophagiennes non prises en charge pour des raisons d’organisation régionale. Il consulte les mardis et vendredis après-midi sur rendez-vous ( c.delmas@bordeaux.unicancer.fr ou e.deney@bordeaux.unicancer.fr). Il participe à la Réunion de Concertation Pluridisciplinaire des Tumeurs Digestives qui se réunit les lundis et jeudis soir. En plus des prises en charge premières, le Professeur Evrard assure une consultation et une RCP de recours pour l’ensemble de la Région Aquitaine, conformément aux dispositions du Plan Cancer pour les cas d’emblée complexes et les situations de récidive (métastases hépatiques, cancer du rectum, carcinoses péritonéales, pancréas, etc.)
Le Professeur Evrard dispense des cours à la Faculté de Médecine de Bordeaux. Il participe à de nombreux enseignements post-universitaires et organise en particulier le cours avancé européen de l’ESSO : « Management of colorectal liver metastases » en collaboration avec le Pr. Graeme Poston, de l’Université de Liverpool.
1.1. La recherche à Bergonié
Au sien du Groupe Digestif, le Professeur Evrard développe avec le Docteur Desolneux les programmes chirurgicaux qui s’intègrent dans les thématiques du Groupe Digestif.
Pour les métastases hépatiques du cancer colorectal, le protocole ARF2003 a permis (PHRC 2003) d’établir la première série prospective de lésions non résecables, opérées par résection plus ablation par radiofréquences. L’ablathermie peropératoire est depuis considérée dans les programmes de recherche clinique comme une procédure curative qui permet de traiter davantage de patients notamment ceux souffrants de lésions complexes et nombreuses. Ces résultats ont été consacrés par un prix de la meilleure contribution scientifique au congrès de la société internationale de chirurgie hépato-biliaire et pancréatique à Cape Town en Avril 2011. Les résultats d’ARF2003 ont été ensuite confirmés à grande échelle par une étude multicentrique menée entre l’institut et trois autres centres : le Memorial de New-York, l’hôpital universitaire d’Aarhus au Danemark et l’Université de Aintree Liverpool. Les résultats de cette étude ont été présentés à l’ASCO à Chicago en 2013, au congrès international de chirurgie hépatique de Séoul en 2014 (IHPBA) et sont publiés dans Plos One. L’essai ULIIS a quant à lui montré l’intérêt de l’échographie de contraste peroperatoire pour diagnostiquer encore plus de lésions durant la chirurgie (en cours de publication). Ainsi, le groupe a largement contribué au succès international du concept de chirurgie hépatique avec épargne parenchymateuse s’opposant à la pratique des hépatectomies extensives prophylactiques.
Centre de référence régional pour les métastases péritonéales (carcinomatose), le Groupe Digestif avait initié un essai original, COCHISE, qui étudiait l’association d’une chirurgie radicale et complète à une chimiothérapie puissante doublée d’un anticorps bloquant les cellules en réplication. L’idée était de supprimer la chimiothérapie intrapéritonéale hyperthermique (CHIP) proposée par certains à l’issu de la chirurgie. En raison de critères d’inclusion trop stricts, l’essai a dû être clôturé. Toutefois, l’équipe a publié une série de 50 patients ayant bénéficié du même traitement hors protocole et les résultats confirment l’hypothèse de la futilité de la CHIP (Plos One 2015)
De gros progrès ont été réalisés ces 20 dernières années pour le cancer du rectum, notamment le risque de récidive pelvien est passé de 30 à moins de 5 % et ce grâce à une meilleure technique chirurgicale doublée des progrès de la radiothérapie. Toutefois les cancers des moyens et bas rectums sont traités aujourd’hui moyennant une morbidité élevée et une altération importante de la qualité de vie. Un nouveau type de rétablissement de la continuité après ablation complète du rectum, l’anastomose coloanale différée pourrait permettre de réduire la morbidité et surtout de supprimer le recours systématique à la pratique d’un anus artificiel temporaire préventif. De plus cette intervention induit des coûts beaucoup plus faibles. Le Groupe Digestif réalise l’essai CASCADOR qui va tenter de démontrer sur une base multicentrique et prospective l’intérêt de cette technique (publication prévue fin 2017)
Dans la même idée d’améliorer la qualité de vie des patients opérés d’un cancer du rectum, le Groupe Digestif étudie les conséquences du traitement radiothérapique et chirurgical sur la fonction érectile. Le protocole METEORR grâce à un enregistrement polysomnographique est à même de discriminer les troubles fonctionnels accessibles à un traitement médicamenteux des troubles organiques. Le diagnostic précoce de ces troubles permet ainsi de prévenir la fixation des troubles érectiles et oriente leur prise en charge.
Le protocole ZAK 0 (Unité INSERM Vinco) sera une des toutes premières phase 0 ouvertes en France. Le but est de tester une nouvelle thérapie ciblée, en l’occurrence le nilotinib, sur des tumeurs coliques humaines devant être traitées chirurgicalement et dont le prise en charge n’est pas modifiée pour respecter l’éthique. Ce type d’approche devrait permettre de déterminer si la molécule confirme chez l’homme l’intérêt in vitro.
D’autres essais académiques ou industriels sont ouverts à l’institut dans la chirurgie des tumeurs digestives. Merci d’en consulter la liste régulièrement actualisée sur notre site internet.
1.2. La recherche EUROPEENNE (EORTC + ESSO)
Le Professeur Evrard est particulièrement impliqué dans la méthodologie des essais cliniques en chirurgie pour lesquels il prône la primauté du caractère prospectif de la démarche sur la randomisation. Ses idées ont fait l’objet d’une mise au point dans la prestigieuse revue Nature Reviews in Clinical Oncoloy . En 2014, il a pris la direction de la section recherche de l’ESSO (European Society of Surgical Oncology) en collaboration avec l’EORTC. Il est ainsi investigateur principal de deux essais de phase 4 portant sur l’amélioration de la qualité de la chirurgie des métastases hépatiques : CLIMB EORTC 1209 et DREAM EORTC 1527. Ces deux premiers essais menés en collaboration avec les meilleures équipes européennes inaugurent une plateforme de recherche chirurgicale, SURCARE, qui dédira des moyens financiers et humains inédits à la recherche chirurgicale conte le cancer. DREAM a d’ores et déjà élargi son assise au Japon avec le JCOG et aux USA avec le MD Anderson de Houston.
Le but de la recherche clinique tanslationnelle est de transférer à la clinique, au bénéfice du patient, les résultats de la recherche biologique obtenue en laboratoire. Elle est donc basée sur un binôme clinicien/chercheur. Le Groupe Digestif de l’IB a établi ce lien avec l’équipe de Majid Kathib (Directeur de Recherche INSERM (Unité 1029), Chair d’Excellence de l’Université de Bordeaux) sur le thème des Processus Métastatiques.
Afin de cibler un traitement efficace contre les métastases des cancers viscéraux, une compréhension de leur biologie est nécessaire. Nous avons montré pour la première fois dans des études récentes, confirmées ensuite par d’autres chercheurs, que les convertases peuvent être considérées comme de nouvelles cibles pour le traitement de certains cancers et métastases. Les convertases sont des enzymes impliquées dans la maturation et l’activation de plusieurs protéines dont certaines sont responsables du caractère métastatique des cellules tumorales comme les facteurs de croissance, les molécules d’adhésion et les protéases. Le but de ce projet de recherche est d’évaluer l’importance clinique de ces enzymes dans la progression tumorale et la formation des métastases afin d’utiliser leurs inhibiteurs comme de potentiels agents antitumoraux et/ou antimétastatiques.
Une première molécule visant les cancers du colon et du pancréas vient d’être licenciée par une compagnie pharmaceutique (4PPharma) et d’autres viennent d’être brevetées dans l’attente de leur développement préclinique.
Récemment, le Groupe Digestif de Bergonié et le groupe de Majid Khatib ont été sélectionnés par la Ligue Nationale contre le cancer pour intégrer le programme « Carte d’identité des Tumeurs » en collaboration le Professeur Laurent-Puig de Paris (HEGP). Une étude translationnelle satellite de l’étude DREAM va être lancée pour mieux comprendre l’hétérogénéité génomique entre tumeurs primitives colorectales et leurs métastases.
Tomé M, Pappalardo A, Soulet F, López JJ, Olaizola J, Leger Y, Dubreuil M, Mouchard A, Fessart D, Delom F, Pitard V, Bechade D, Fonck M, Rosado JA, Ghiringhelli F, Déchanet-Merville J, Soubeyran I, Siegfried G, Evrard S, Khatib AM. Cancer Res. 2019 Oct 1;79(19):5008-5021. doi: 10.1158/0008-5472.CAN-19-0086. Epub 2019 Jul 29.
A novel mechanism of mTOR inhibition displacing phosphatidic acid induces enhanced cytotoxicity specifically in cancer cells. Tra-Ly Nguyen, Marie-Julie Nokin, Maxim Egorov, Mercedes Tomé, Clément Bodineau, Carmelo Di Primo, Lætitia Minder, Joanna Wdzieczak-Bakala, Maria Concepcion Garcia-Alvarez, Jérôme Bignon, Odile Thoison, Bernard Delpech, Georgiana Surpateanu, Yves-Michel Frapart, Fabienne Peyrot, Kahina Abbas, Silvia Terés, Serge Evrard, Abdel-Majid Khatib, Pierre Soubeyran, Bogdan I. Iorga, Raúl V. Durán, and Pascal Collin. Cancer Research 2018;78(18):5384-5397
Parenchymal sparing surgery brings treatment of colorectal liver metastases into the precision medecine era. Evrard S, Torzilli G, Caballero C, Bonhomme B. European Journal of Cancer 2018; 104: 195-200.
From a Comic Opera to Surcare an Open Letter to Whom Clinical Research in Surgery Is a Concern: Announcing the Launch of SURCARE. Evrard S, Audisio R, Poston G, Caballero C, Kataoka K, Fontein D, Collette L, Nakamura K, Fukuda H, Lacombe D. Ann Surg. 2016 Dec;264(6):911-912.
Collaboration between EORTC and JCOG-how to accelerate global clinical research partnership. Kataoka K, Nakamura K, Caballero C, Evrard S, Negrouk A, Shiozawa M, Collette L, Fukuda H, Lacombe D. Jpn J Clin Oncol. 2016 Oct 20
Apelin: an antithrombotic factor that inhibits platelet function. Adam F, Khatib AM, Lopez JJ, Vatier C, Turpin S, Muscat A, Soulet F, Aries A, Jardin I, Bobe R, Stepanian A, de Prost D, Dray C, Rosado JA, Valet P, Feve B, Siegfried G. Blood. 2016 Feb 18;127(7):908-20.
All-trans retinoic acid targets gastric cancer stem cells and inhibits patient-derived gastric carcinoma tumor growth. Nguyen PH, Giraud J, Staedel C, Chambonnier L, Dubus P, Chevret E, Bœuf H, Gauthereau X, Rousseau B, Fevre M, Soubeyran I, Belleannée G, Evrard S, Collet D, Mégraud F, Varon C. Oncogene. 2016 Oct 27;35(43):5619-5628.
Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer. Lutz MP, Zalcberg JR, Glynne-Jones R, Ruers T, Ducreux M, Arnold D, Aust D, Brown G, Bujko K, Cunningham C, Evrard S, Folprecht G, Gerard JP, Habr-Gama A, Haustermans K, Holm T, Kuhlmann KF, Lordick F, Mentha G, Moehler M, Nagtegaal ID, Pigazzi A, Puciarelli S, Roth A, Rutten H, Schmoll HJ, Sorbye H, Van Cutsem E, Weitz J, Otto F. Eur J Cancer. 2016 Aug;63:11-24.
Characterization of biomarkers of tumorigenic and chemoresistant cancer stem cells in human gastric carcinoma. Nguyen PH, Giraud J, Chambonnier L, Dubus P, Wittkop L, Belleannée G, Collet D, Soubeyran I, Evrard S, Rousseau B, Dugot-Senant N, Mégraud F, Mazurier F, Varon C. Clin Cancer Res. 2016 Sep 12. pii: clincanres.2157.2015
What can we learn from oncology surgical trials? Evrard S, McKelvie-Sebileau P, van de Velde C, Nordlinger B, Poston G. Nat Rev Clin Oncol. 2016 Jan;13(1):55-62
In favour of One-Stage Strategy (OSS). Evrard S. Eur J Surg Oncol. 2015 Dec;41(12):1568-9
Inhibition of Gastric Tumor Cell Growth Using Seed-targeting LNA as Specific, Long-lasting MicroRNA Inhibitors.Staedel C, Varon C, Nguyen PH, Vialet B, Chambonnier L, Rousseau B, Soubeyran I, Evrard S, Couillaud F, Darfeuille F. Mol Ther Nucleic Acids. 2015 Jul 7;4:e246
Cytoreductive surgery of colorectal peritoneal metastases: outcomes after complete cytoreductive surgery and systemic chemotherapy only. Désolneux G, Mazière C, Vara J, Brouste V, Fonck M, Béchade D, Bécouarn Y, Evrard S. PLoS One. 2015 Mar 31;10(3):e0122816.
Limits of colorectal liver metastases resectability: how and why to overcome them. Evrard S Recent Results Cancer Res. 2014;203:213-29
Patterns of complications following intraoperative radiofrequency ablation for liver metastases. Desolneux G, Jeremy V, Razafindratsira T, Isambert M, Brouste V, McKelvie-Sebileau P, Evrard S. HPB 2014, 16, 1002–1008.
Combined Ablation and Resection (CARe) as an Effective Parenchymal Sparing Treatment for Extensive Colorectal Liver Metastases. Evrard S, Poston G, Kissmeier-Nielsen P, Diallo A, Desolneux G, Brouste V et al. PLoS One. 2014 Dec 8;9(12):e114404.
Sfaxi F,Scamuffa N,Lalou C,Ma J, Metrakos P, Siegfried G,Ragg H,Bikfalvi A, Khatib AM. Repression of liver colorectal metastasis by the serpin spn4Aa naturally occurring inhibitor of the constitutive secretory proprotein convertases. Oncotarget. 2014 Jun 30;5(12):4195-210.
Use of Bioresorbable Membranes to Reduce Abdominal and Peri-Hepatic Adhesions in Two-Stage Hepatectomy of Liver Metastases from Colorectal Cancer: Results of a Prospective Randomized controlled Phase II Trial. Dupré A, Lefranc A, Buc E, Delpero JR, Quenet F, Passot G, Evrard S, Rivoire M. Annals of Surgery 2013; 258: 30-6.
Liver metastases in close contact to hepatic veins ablated under vascular exclusion. Evrard S, Brouste V, McKelvie-Sebileau P, Desolneux G. European Journal of Surgical Oncology 2013 ; 39 : 1400-6
Unresectable colorectal cancer liver metastases treated by intraoperative radiofrequency ablation with or without resection: the ARF2003 Study. Evrard S, Rivoire M, Arnaud JP, Lermite E, Bellera C, Brunet R, Fonck M, Bécouarn Y, Mathoulin-Pélissier S.British Journal of Surgery 2012 ; 99 : 558-565.
Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach? Correspondence. Evrard S, Mazière C, Desolneux G. Lancet Oncology 2012 ; 13 : e462 – e463
Scamuffa N, Siegfried G, Bontemps Y, Ma L, Basak A, Cherel G, Calvo F, Seidah NG, Khatib AM. Selective inhibition of proprotein convertases represses the metastatic potential of human colorectal tumor cells. J Clin Invest. 2008 Jan;118(1):352-63.
– Limits in colorectal liver metastases resectability and how to overcome them? Conference. 2nd St Gallen EORTC Gastrointestinal Cancer conference 2014 – 7 March 2014 St Gallen
– From Anatomy to Oncology: A dialectical story of Colorectal Liver Metastases Treatment. 6th International Symposium on Abdominal Metastatic Cancer. Regensburg , April 2014.
– Toward parenchyma-sparing surgery to treat advanced colorectal liver metastases: The concept of care. 3rd International Gastrointestinal and Liver Oncology Conference – Cairo Egypt 15-16 June 2014
– Oncosurgical approach of unresectable colorectal liver metastases: time for surgical de-escalation? Evrard S. International congress of IHPBA, Seoul, March 2014.
-Borderline resectable colorectal liver metastases : One stage CARe. ESSO 34, Liverpool, October 2014.
– Liver surgery after neo adjuvant chemotherapy. Serge Evrard. ESO-ESSO Masterclass in Colorectal Cancer Surgery Warshaw, March 2015
– Atropho-hypertrophy techniques and one or two–stage strategies to treat advances colorectal liver metastases. 1st Simposio de Oncologica, 29-30 April 2015 Rio de Janeiro
– Traitement néo-adjuvant de conversion des tumeurs pancréatiques non résécables.
Congrès de la Société Française du Cancer, Paris, Juin 2015.
– Radiologic requirements, clinical parameters, blood results, history, patients needs. ESSO Liver course. Rudolfstiftung Hospital, Vienna, September 2015
– Resections techniques and devices. ESSO Liver course. Rudolfstiftung Hospital, Vienna, September 2015
– Rethinking clinical research in surgical oncology. From comics opera to quality control. Conference: EYSAC Networking Dinner. ECCO/ESMO/ESSO congress Vienna, September 2015, 26th.
– The Surcare spirit: CLIMB and DREAM. Royal College of Surgeons International Surgical Trials Initiative Event. Royal College of Surgeon London; 6/7 June 2016
– Combined ablation and resection of colorectal liver metastases: chances and pitfalls. 8th Abdominal Metastatic Cancer 2016. Regensburg July 2016
– Succeeding in surgical oncology research –tips and tricks from a master. EYSAC scientific symposium. ESSO Congress Krakow 2016 (September)
– Plea for a new deal in surgical oncology. Clinical research in surgical oncology. ESSO Congress Krakow 2016 (September)
– Revisiting clinical research in surgical oncology: a plea for new directions. WorldCancerCongress, Union Internationale contre le Cancer, Paris Novembre 2016
– Educational Track/Professional Development Session. Surgical oncology perspective. My advices to a young colleague, Amsterdam. ECCO Meeting, January 2017
– Colorectal liver metastases: how to build a strategy? 6th International Gastrointestinal Liver and Urology Conference. Cairo. May 4-5, 2017
– Clinical research and evidence based medecine.Minimal standards & Quality assurance in oncology. Focus on solid tumours. Padova, October 17, 2017.
– EU and Japan embarking together for research in surgical oncology. Conference JCOG/EORTC symposium. National Cancer Center Hospital. Tokyo December 1-2, 2017.
– Characterization of biomarkers of tumorigenic and chemoresistant cancer stem cells in human gastric carcinoma. Nguyen PH, Giraud J, Chambonnier L, Dubus P, Wittkop L, Belleannée G, Collet D, Soubeyran I, Evrard S, Rousseau B, Senant-Dugot N, Mégraud F, Mazurier F, Varon C. Clinical Cancer Research 2017; 23(6):1586-1597.
– Collaboration between EORTC and JCOG — how to accelerate global clinical research partnership? Kataoka K, Nakamura K, Caballero C, Evrard S, Negrouk A, Shiozawa M, Collette L, Fukuda H, Lacombe D. Japanese Journal of Clinical Oncology 2017 ; 47 (2) : 164-169.
– Regulation of the proprotein convertases expression and activity during regenerative angiogenesis: Role of hypoxia-inducible factor (HIF). Ma J, Evrard S, Siegfried G, Khatib AM. European Journal of Cell Biology 2017 ; 96 (5) : 457-468.
– Parenchymal sparing surgery for colorectal liver metastases: the need for a common definition. Desjardin M, Desolneux G, Brouste V, Degrandi O, Bonhomme B, Fonck M., Bécouarn Y, Béchade D, Evrard S. European Journal of Surgical Oncology 2017 ; 43 (12) : 2285-2291.
– Multidisciplinary quality assurance and control in oncological trials: Perspectives from European Organisation for Research and Treatment of Cancer (EORTC). Lacombe D, Coens C, de Balincourt C, Licitra L, den Dulk M, Machiels JP, Weber D, Spahn M, Salgado R, Kasper B, Hau P, Betsou F, Kataoka K, Caballero C, Liu Y, Hurkmans C, Evrard S. European Journal of Cancer 2017 ; 86 : 91-100.
– Impact of RAS mutations in metastatic colorectal cancer after potentially curative resection: does site of metastases matter? Passot G, Kim BJ, Glehen O, Mehran RJ, Kopetz SE, Goere D, Overman MJ, Pocard M, Marchal F, Conrad C, Aloia TA, Vauthey JN, Chun YS, BIG-RENAPE Working Group. Annals of Surgical Oncology 2018 ; 25 (1) : 179-187.
– A novel mechanism of mTOR inhibition displacing phosphatidic acid induces enhanced cytotoxicity specifically in cancer cells.Tra-Ly Nguyen, Marie-Julie Nokin, Maxim Egorov, Mercedes Tomé, Clément Bodineau, Carmelo Di Primo, Lætitia Minder, Joanna Wdzieczak-Bakala, Maria Concepcion Garcia-Alvarez, Jérôme Bignon, Odile Thoison, Bernard Delpech,Georgiana Surpateanu, Yves-Michel Frapart, Fabienne Peyrot, Kahina Abbas, Silvia Terés, Serge Evrard, Abdel-Majid Khatib, Pierre Soubeyran, Bogdan I. Iorga, Raúl V. Durán, and Pascal Collin Cancer Research 2018; 78(18):5384-5397.
– Parenchymal sparing surgery brings treatment of colorectal liver metastases into the precision medecine era.
Evrard S, Torzilli G, Caballero C, Bonhomme B. European Journal of Cancer 2018; 104: 195-200.
– Clinical Research in Surgical Oncology/The need for a reset! Evidence based medecine, Master de Sinologia / Barcelona University Barcelone Mai 2018
English version
Serge EVRARD is Professor of Cancerology (surgery – exceptional class) at the University of Bordeaux. At the Institute, he coordinates the Digestive Tumors Group and the Department of Surgery.
After studying medicine in Nancy (1978-1984), Serge Evrard obtained a doctorate in medicine and a diploma specializing in visceral surgery (1985-1990) in Strasbourg. Laureate of the Faculty, he obtained his doctorate in sciences from the University Paris VII and his Habilitation à Diriger les Recherches (HDR) in 1993. He was named Professor of the Universities-Hospital Practitioner in 1994. In 1999, he joined the Institut Bergonié to complete and develop the Digestive Group. At the national level, he chaired the Société Française du Cancer and the la Société Française de Chirurgie Oncologique, which he co-founded in 2007. At the international level, he is a member of the executive board of the European Society of Surgical Oncology, where he also directs clinical research. In 2014, he created the surgical oncology research platform SURCARE, a collaboration between European Society of Surgical Oncology (ESSO) and the European Organization for Research and Treatment of Cancer (EORTC).
This is a short animated video to explain the positive impact of specialised surgery in the fight against cancer.
PRIMARY CARE
Professor Evrard specializes in the management of digestive tumors: stomach, small intestine, colon, rectum, anus, liver, pancreas and peritoneum, excluding eosophageal tumors (not taken care of for reasons of regional organization). He holds consultations every Tuesday and Friday afternoon by appointment (c.fontaine@bordeaux.unicancer.fr ). He participates in the multidisciplinary meeting of Digestive Tumors, which meets on Monday and Thursday evenings. In addition to primary care, Professor Evrard ensures consultations and multidisciplinary meetings for the whole of the Aquitaine Region, in accordance with the Cancer Plan for complex cases from the outset and relapses (hepatic metastases, rectal cancer, peritoneal carcinomas, pancreas, etc.).
TEACHING
Professor Evrard teaches at the Faculty of Medicine of Bordeaux. He participates in numerous postgraduate courses and organizes, in particular, the ESSO’s European advanced course: « Management of colorectal liver metastases » in collaboration with Prof. Graeme Poston, University of Liverpool.
Contact Serge Evrard:
– For an appointment: c.fontaine@bordeaux.unicancer.fr
– For university or clinical enquiries: s.evrard@bordeaux.unicancer.fr
– For question relating to clinical research: e.ducasse@bordeaux.unicancer.fr
RESEARCH
Professor EVRARD is involved in two different areas of research, clinical research and translational biological research
1. Clinical Research
1.1. Research in Bergonié
In his Digestive Group, Professor Evrard developed, with Dr. Desolneux, the surgical programs that integrate into the Digestive Group themes.
For hepatic metastases of colorectal cancer, the ARF2003 protocol allowed (PHRC 2003) establishing the first prospective series of non-resectable lesions, operated by resection plus radiofrequency ablation. Intraoperative ablathermy has since been considered, in clinical research programs, as a curative procedure that can treat patients, especially those suffering from complex and numerous lesions. These results were awarded a best scientific contribution prize at the International Society of Hepato-Biliary and Pancreatic Surgery congress, in Cape Town in April 2011. The results of ARF2003 were then confirmed on a large scale by a multicenter study conducted between the institute and three other centers: the Memorial of New York, the University Hospital of Aarhus in Denmark and the University of Aintree, Liverpool. The results of this study were presented at the ASCO in Chicago in 2013, at the International Congress of Seoul Hepatic Surgery in 2014 (IHPBA) and are published in Plos One. The ULIIS trial showed the interest of intraoperative contrast ultrasound to diagnose even more lesions during surgery (in the process of being published). Thus, the group has largely contributed to the international success of the liver surgery with parenchymal sparing concept opposing extensive prophylactic hepatectomies.
As a regional reference center for peritoneal metastases (carcinomatosis), the Digestive Group initiated an original trial, COCHISE, which studied the combination of radical and complete surgery with potent chemotherapy coupled with an antibody that blocks replicating cells. The idea was to suppress hyperthermic intraperitoneal chemotherapy (CHIP) proposed by some at the end of surgery. Due to too strict inclusion criteria, the trial had to be closed. However, the team published an article on a series of 50 patients who benefited from the same non-protocol treatment and the results confirm the futility of CHIP hypothesis (Plos One 2015).
Much progress has been made in the past 20 years for rectal cancer; in particular, the risk of pelvic recurrence has decreased from 30 to less than 5% thanks to better surgical techniques coupled with advances in radiotherapy. However, cancers of the middle and lower rectum are treated today despite high morbidity and an essential alteration of the quality of life. A new type of restoration of continuity after complete ablation of the rectum, delayed coloanal anastomosis, could reduce morbidity and above all eliminate the systematic use of a temporary artificial preventive anus. Moreover, this involves much lower costs. The Digestive Group is carrying out the CASCADOR trial which will try to demonstrate, on a multicenter and prospective basis, the interest of this technique (publication expected at the end of 2017).
With the same idea of improving the quality of life of the patients operated for rectal cancer, the Digestive Group studies the consequences of radiotherapy and surgical treatment on erectile function. The METEORR protocol, thanks to a polysomnographic recording, is able to discriminate the functional disorders accessible to a medicinal treatment from organ disorders. The early diagnosis of these disorders therefore allows fixing erectile dysfunction and guides their management.
The protocol ZAK 0 (Unit INSERM Vinco) will be one of the very first phase 0 opened in France. The aim is to test a new targeted therapy, in this case nilotinib, on human colic tumors to be treated surgically and whose management is not modified to respect ethics. This type of approach should make it possible to determine whether the molecule works in vitro in humans.
Other academic or industrial trials in the surgery of digestive tumors are open to the institute. Please check the updated list regularly on our website.
1.2. EUROPEAN research (EORTC + ESSO)
Professor Evrard is particularly involved in the methodology of clinical trials in surgery for which he advocates the importance of the prospective nature of the approach on randomization. His ideas have been in focus in the prestigious review of Nature Reviews in Clinical Oncoloy. In 2014, he headed the research section of ESSO in collaboration with the EORTC. He is the principal investigator of two phase 4 trials to improve the quality of hepatic metastasis surgery: CLIMB EORTC 1209 and DREAM EORTC 1527. These two foremost trials conducted in collaboration with the best European surgical research teams, SURCARE, will dedicate unprecedented financial and human resources to surgical research related to cancer. DREAM has already expanded its base in Japan with the JCOG and in the USA with the MD Anderson Cancer Center, Houston.
2. Translational Biological Research
The aim of translational clinical research is to transfer to the clinic, to benefit patients, the results of biological research obtained in the laboratory. It is therefore based on a clinician / researcher pairing. The IB Digestive Group has established this link with Majid Kathib’s team (INSERM Research Director (Unit 1029), Chair of Excellence at the University of Bordeaux) on the Metastatic Processes theme.
In order to target an effective treatment against metastases of visceral cancers, an understanding of their biology is necessary. We have shown for the first time in recent studies, confirmed by other researchers, that convertases can be considered as new targets for the treatment of certain cancers and metastases. Convertases are enzymes involved in the maturation and activation of several proteins, such as growth factors, adhesion molecules and proteases, some of which are responsible for the metastatic character of tumor cells. The aim of this research project is to evaluate the clinical significance of these enzymes in tumor progression and metastasis formation in order to use their inhibitors as potential anti-tumor and / or anti-metastatic agents.
A first molecule targeting cancers of the colon and pancreas has just been licensed by a pharmaceutical company (4PPharma) and others have just been patented, pending their preclinical development.
Recently, the Digestive Group of Institut Bergonié and Majid Khatib’s group have been selected by the National League Against Cancer to integrate into the « Tumor Identity Card » program in collaboration with Professor Laurent-Puig of Paris (HEGP). A satellite translational study of the DREAM study will be launched to better understand the genomic heterogeneity between primary colorectal tumors and their metastases.
PUBLICATIONS
– Tomé M, Pappalardo A, Soulet F, López JJ, Olaizola J, Leger Y, Dubreuil M, Mouchard A, Fessart D, Delom F, Pitard V, Bechade D, Fonck M, Rosado JA, Ghiringhelli F, Déchanet-Merville J, Soubeyran I, Siegfried G, Evrard S, Khatib AM. Cancer Res. 2019 Oct 1;79(19):5008-5021. doi: 10.1158/0008-5472.CAN-19-0086. Epub 2019 Jul 29.
– A novel mechanism of mTOR inhibition displacing phosphatidic acid induces enhanced cytotoxicity specifically in cancer cells. Tra-Ly Nguyen, Marie-Julie Nokin, Maxim Egorov, Mercedes Tomé, Clément Bodineau, Carmelo Di Primo, Lætitia Minder, Joanna Wdzieczak-Bakala, Maria Concepcion Garcia-Alvarez, Jérôme Bignon, Odile Thoison, Bernard Delpech, Georgiana Surpateanu, Yves-Michel Frapart, Fabienne Peyrot, Kahina Abbas, Silvia Terés, Serge Evrard, Abdel-Majid Khatib, Pierre Soubeyran, Bogdan I. Iorga, Raúl V. Durán, and Pascal Collin. Cancer Research 2018;78(18):5384-5397
– Parenchymal sparing surgery brings treatment of colorectal liver metastases into the precision medecine era. Evrard S, Torzilli G, Caballero C, Bonhomme B. European Journal of Cancer 2018; 104: 195-200.
– From a Comic Opera to Surcare an Open Letter to Whom Clinical Research in Surgery Is a Concern: Announcing the Launch of SURCARE. Evrard S, Audisio R, Poston G, Caballero C, Kataoka K, Fontein D, Collette L, Nakamura K, Fukuda H, Lacombe D. Ann Surg. 2016 Dec;264(6):911-912.
– Collaboration between EORTC and JCOG-how to accelerate global clinical research partnership. Kataoka K, Nakamura K, Caballero C, Evrard S, Negrouk A, Shiozawa M, Collette L, Fukuda H, Lacombe D. Jpn J Clin Oncol. 2016 Oct 20
– Apelin: an antithrombotic factor that inhibits platelet function. Adam F, Khatib AM, Lopez JJ, Vatier C, Turpin S, Muscat A, Soulet F, Aries A, Jardin I, Bobe R, Stepanian A, de Prost D, Dray C, Rosado JA, Valet P, Feve B, Siegfried G. Blood. 2016 Feb 18;127(7):908-20.
– All-trans retinoic acid targets gastric cancer stem cells and inhibits patient-derived gastric carcinoma tumor growth. Nguyen PH, Giraud J, Staedel C, Chambonnier L, Dubus P, Chevret E, Bœuf H, Gauthereau X, Rousseau B, Fevre M, Soubeyran I, Belleannée G, Evrard S, Collet D, Mégraud F, Varon C. Oncogene. 2016 Oct 27;35(43):5619-5628.
– Second St. Gallen European Organisation for Research and Treatment of Cancer Gastrointestinal Cancer Conference: consensus recommendations on controversial issues in the primary treatment of rectal cancer. Lutz MP, Zalcberg JR, Glynne-Jones R, Ruers T, Ducreux M, Arnold D, Aust D, Brown G, Bujko K, Cunningham C, Evrard S, Folprecht G, Gerard JP, Habr-Gama A, Haustermans K, Holm T, Kuhlmann KF, Lordick F, Mentha G, Moehler M, Nagtegaal ID, Pigazzi A, Puciarelli S, Roth A, Rutten H, Schmoll HJ, Sorbye H, Van Cutsem E, Weitz J, Otto F. Eur J Cancer. 2016 Aug;63:11-24.
– Characterization of biomarkers of tumorigenic and chemoresistant cancer stem cells in human gastric carcinoma. Nguyen PH, Giraud J, Chambonnier L, Dubus P, Wittkop L, Belleannée G, Collet D, Soubeyran I, Evrard S, Rousseau B, Dugot-Senant N, Mégraud F, Mazurier F, Varon C. Clin Cancer Res. 2016 Sep 12. pii: clincanres.2157.2015
– What can we learn from oncology surgical trials? Evrard S, McKelvie-Sebileau P, van de Velde C, Nordlinger B, Poston G. Nat Rev Clin Oncol. 2016 Jan;13(1):55-62
– In favour of One-Stage Strategy (OSS). Evrard S. Eur J Surg Oncol. 2015 Dec;41(12):1568-9
– Inhibition of Gastric Tumor Cell Growth Using Seed-targeting LNA as Specific, Long-lasting MicroRNA Inhibitors.Staedel C, Varon C, Nguyen PH, Vialet B, Chambonnier L, Rousseau B, Soubeyran I, Evrard S, Couillaud F, Darfeuille F. Mol Ther Nucleic Acids. 2015 Jul 7;4:e246
– Cytoreductive surgery of colorectal peritoneal metastases: outcomes after complete cytoreductive surgery and systemic chemotherapy only. Désolneux G, Mazière C, Vara J, Brouste V, Fonck M, Béchade D, Bécouarn Y, Evrard S. PLoS One. 2015 Mar 31;10(3):e0122816.
– Limits of colorectal liver metastases resectability: how and why to overcome them. Evrard S Recent Results Cancer Res. 2014;203:213-29
– Patterns of complications following intraoperative radiofrequency ablation for liver metastases. Desolneux G, Jeremy V, Razafindratsira T, Isambert M, Brouste V, McKelvie-Sebileau P, Evrard S. HPB 2014, 16, 1002–1008.
– Combined Ablation and Resection (CARe) as an Effective Parenchymal Sparing Treatment for Extensive Colorectal Liver Metastases. Evrard S, Poston G, Kissmeier-Nielsen P, Diallo A, Desolneux G, Brouste V et al. PLoS One. 2014 Dec 8;9(12):e114404.
– Sfaxi F,Scamuffa N,Lalou C,Ma J, Metrakos P, Siegfried G,Ragg H,Bikfalvi A, Khatib AM. Repression of liver colorectal metastasis by the serpin spn4Aa naturally occurring inhibitor of the constitutive secretory proprotein convertases. Oncotarget. 2014 Jun 30;5(12):4195-210.
– Use of Bioresorbable Membranes to Reduce Abdominal and Peri-Hepatic Adhesions in Two-Stage Hepatectomy of Liver Metastases from Colorectal Cancer: Results of a Prospective Randomized controlled Phase II Trial. Dupré A, Lefranc A, Buc E, Delpero JR, Quenet F, Passot G, Evrard S, Rivoire M. Annals of Surgery 2013; 258: 30-6.
– Liver metastases in close contact to hepatic veins ablated under vascular exclusion. Evrard S, Brouste V, McKelvie-Sebileau P, Desolneux G. European Journal of Surgical Oncology 2013 ; 39 : 1400-6
– Unresectable colorectal cancer liver metastases treated by intraoperative radiofrequency ablation with or without resection: the ARF2003 Study. Evrard S, Rivoire M, Arnaud JP, Lermite E, Bellera C, Brunet R, Fonck M, Bécouarn Y, Mathoulin-Pélissier S.British Journal of Surgery 2012 ; 99 : 558-565.
– Cytoreductive surgery plus hyperthermic perioperative chemotherapy to treat peritoneal metastases from colorectal cancer: standard of care or an experimental approach? Correspondence. Evrard S, Mazière C, Desolneux G. Lancet Oncology 2012 ; 13 : e462 – e463
– Scamuffa N, Siegfried G, Bontemps Y, Ma L, Basak A, Cherel G, Calvo F, Seidah NG, Khatib AM. Selective inhibition of proprotein convertases represses the metastatic potential of human colorectal tumor cells. J Clin Invest. 2008 Jan;118(1):352-63.
CONFERENCES
– Limits in colorectal liver metastases resectability and how to overcome them? Conference. 2nd St Gallen EORTC Gastrointestinal Cancer conference 2014 – 7 March 2014 St Gallen
– From Anatomy to Oncology: A dialectical story of Colorectal Liver Metastases Treatment. 6th International Symposium on Abdominal Metastatic Cancer. Regensburg , April 2014.
– Toward parenchyma-sparing surgery to treat advanced colorectal liver metastases: The concept of care. 3rd International Gastrointestinal and Liver Oncology Conference – Cairo Egypt 15-16 June 2014
– Oncosurgical approach of unresectable colorectal liver metastases: time for surgical de-escalation? Evrard S. International congress of IHPBA, Seoul, March 2014.
– Borderline resectable colorectal liver metastases : One stage CARe. ESSO 34, Liverpool, October 2014.
– Liver surgery after neo adjuvant chemotherapy. Serge Evrard. ESO-ESSO Masterclass in Colorectal Cancer Surgery Warshaw, March 2015
– Atropho-hypertrophy techniques and one or two–stage strategies to treat advances colorectal liver metastases. 1st Simposio de Oncologica, 29-30 April 2015 Rio de Janeiro
– Traitement néo-adjuvant de conversion des tumeurs pancréatiques non résécables. Congrès de la Société Française du Cancer, Paris, Juin 2015.
– Radiologic requirements, clinical parameters, blood results, history, patients needs. ESSO Liver course. Rudolfstiftung Hospital, Vienna, September 2015
– Resections techniques and devices. ESSO Liver course. Rudolfstiftung Hospital, Vienna, September 2015
– Rethinking clinical research in surgical oncology. From comics opera to quality control. Conference: EYSAC Networking Dinner. ECCO/ESMO/ESSO congress Vienna, September 2015, 26th.
– The Surcare spirit: CLIMB and DREAM. Royal College of Surgeons International Surgical Trials Initiative Event. Royal College of Surgeon London; 6/7 June 2016
– Combined ablation and resection of colorectal liver metastases: chances and pitfalls. 8th Abdominal Metastatic Cancer 2016. Regensburg July 2016
– Succeeding in surgical oncology research –tips and tricks from a master. EYSAC scientific symposium. ESSO Congress Krakow 2016 (September)
– Plea for a new deal in surgical oncology. Clinical research in surgical oncology. ESSO Congress Krakow 2016 (September)
– Revisiting clinical research in surgical oncology: a plea for new directions. WorldCancerCongress, Union Internationale contre le Cancer, Paris November 2016
– Educational Track/Professional Development Session. Surgical oncology perspective. My advices to a young colleague, Amsterdam. ECCO Meeting, January 2017
– Colorectal liver metastases: how to build a strategy? 6th International Gastrointestinal Liver and Urology Conference. Cairo. May 4-5, 2017
– Clinical research and evidence based medecine.Minimal standards & Quality assurance in oncology. Focus on solid tumours. Padova, October 17, 2017.
– EU and Japan embarking together for research in surgical oncology. Conference JCOG/EORTC symposium. National Cancer Center Hospital. Tokyo December 1-2, 2017.
– Characterization of biomarkers of tumorigenic and chemoresistant cancer stem cells in human gastric carcinoma. Nguyen PH, Giraud J, Chambonnier L, Dubus P, Wittkop L, Belleannée G, Collet D, Soubeyran I, Evrard S, Rousseau B, Senant-Dugot N, Mégraud F, Mazurier F, Varon C. Clinical Cancer Research 2017; 23(6):1586-1597.
– Collaboration between EORTC and JCOG — how to accelerate global clinical research partnership? Kataoka K, Nakamura K, Caballero C, Evrard S, Negrouk A, Shiozawa M, Collette L, Fukuda H, Lacombe D. Japanese Journal of Clinical Oncology 2017 ; 47 (2) : 164-169.
– Regulation of the proprotein convertases expression and activity during regenerative angiogenesis: Role of hypoxia-inducible factor (HIF). Ma J, Evrard S, Siegfried G, Khatib AM. European Journal of Cell Biology 2017 ; 96 (5) : 457-468.
– Parenchymal sparing surgery for colorectal liver metastases: the need for a common definition. Desjardin M, Desolneux G, Brouste V, Degrandi O, Bonhomme B, Fonck M., Bécouarn Y, Béchade D, Evrard S. European Journal of Surgical Oncology 2017 ; 43 (12) : 2285-2291.
– Multidisciplinary quality assurance and control in oncological trials: Perspectives from European Organisation for Research and Treatment of Cancer (EORTC). Lacombe D, Coens C, de Balincourt C, Licitra L, den Dulk M, Machiels JP, Weber D, Spahn M, Salgado R, Kasper B, Hau P, Betsou F, Kataoka K, Caballero C, Liu Y, Hurkmans C, Evrard S. European Journal of Cancer 2017 ; 86 : 91-100.
– Impact of RAS mutations in metastatic colorectal cancer after potentially curative resection: does site of metastases matter? Passot G, Kim BJ, Glehen O, Mehran RJ, Kopetz SE, Goere D, Overman MJ, Pocard M, Marchal F, Conrad C, Aloia TA, Vauthey JN, Chun YS, BIG-RENAPE Working Group. Annals of Surgical Oncology 2018 ; 25 (1) : 179-187.
– A novel mechanism of mTOR inhibition displacing phosphatidic acid induces enhanced cytotoxicity specifically in cancer cells.Tra-Ly Nguyen, Marie-Julie Nokin, Maxim Egorov, Mercedes Tomé, Clément Bodineau, Carmelo Di Primo, Lætitia Minder, Joanna Wdzieczak-Bakala, Maria Concepcion Garcia-Alvarez, Jérôme Bignon, Odile Thoison, Bernard Delpech,Georgiana Surpateanu, Yves-Michel Frapart, Fabienne Peyrot, Kahina Abbas, Silvia Terés, Serge Evrard, Abdel-Majid Khatib, Pierre Soubeyran, Bogdan I. Iorga, Raúl V. Durán, and Pascal Collin Cancer Research 2018; 78(18):5384-5397.
– Parenchymal sparing surgery brings treatment of colorectal liver metastases into the precision medecine era.
Evrard S, Torzilli G, Caballero C, Bonhomme B. European Journal of Cancer 2018; 104: 195-200.
– Clinical Research in Surgical Oncology/The need for a reset! Evidence based medecine, Master de Sinologia / Barcelona University Barcelone May 2018
