ED Sciences de la Vie et de la Santé
Characterization of extrahepatic cholangiocarcinoma and development of proteomic profiling-based diagnostic predictive models
by Arthur MARICHEZ (BoRdeaux Institute of onCology)
The defense will take place at 14h00 - Salle Vasco de Gamma Centre Médico-Chirurgical Magellan Hôpital Haut Lévêque 1 Avenue de Magellan 33600 Pessac
in front of the jury composed of
- Laurence CHICHE - Professeure des universités - praticienne hospitalière - CHU de Bordeaux - Directeur de these
- ASTRID HERRERO - Professeure des universités - praticienne hospitalière - Hôpital Saint-Eloi - CHU de Montpellier - Rapporteur
- PIETRO ADDEO - Professeur des universités - praticien hospitalier - Hôpital Hautepierrre - Hôpitaux Universitaire de Strasbourg - Rapporteur
- Aurélie BEAUFRèRE - Maîtresse de conférences - praticienne hospitalière - Hôpital Beaujon - APHP - Examinateur
- Safi DOKMAK - Professeur des universités - praticien hospitalier - Hôpital Beaujon - APHP - Examinateur
Extrahepatic cholangiocarcinoma (eCCA) is a rare malignancy with poor prognosis, for which diagnostic management remains challenging. This doctoral work aimed to improve the positive and differential diagnosis of this cancer through a proteomic profiling approach. eCCA encompasses two anatomical entities: perihilar cholangiocarcinoma (pCCA), arising at the biliary confluence from the first-order divisions to the origin of the cystic duct, and distal cholangiocarcinoma (dCCA), located in the supraampullary common bile duct. Overall 5-year survival across all stages is below 10%. Although clinical suspicion is straightforward in the setting of jaundice, general deterioration, and biliary stricture on imaging, definitive diagnosis remains elusive: histological examination of endobiliay cytological specimens (CS), the gold standard for positive diagnosis, yields a sensitivity of only approximately 50%. This diagnostic uncertainty exposes patients to repeated and potentially morbid investigations, unnecessary major surgery when the lesion is benign, and delayed initiation of palliative chemotherapy in unresectable disease. In this context, the primary objective of this work was to identify a diagnostic proteomic signature applicable to CS. Proteomic profiling of 38 CS enabled the development of a predictive model based on a stromal signature obtained through cellular deconvolution, whose performance was validated in an internal cohort of 19 patients and an external cohort of 14 patients. A prerequisite step involved the clinico-oncological and proteomic characterization of eCCA from a series of 204 patients operated at Bordeaux University Hospital between 2007 and 2023. This analysis demonstrated that overall survival and recurrence-free survival were comparable between pCCA and dCCA, with anatomical location not being an independent prognostic factor. Proteomic profiling did not distinguish between the two locations, which shared a common activation of epithelial-to-mesenchymal transition pathways, supporting the consideration of these two tumors as a single oncological entity. Beyond positive diagnosis, eCCA management raises the issue of differential diagnosis, particularly for dCCA versus pancreatic ductal adenocarcinoma (PDAC). These two anatomically adjacent cancers can be difficult to distinguish histologically when the tumor invades both the pancreatic parenchyma and the common bile duct, leading to classification as "pancreatobiliary" adenocarcinomas (PB-ADC). This diagnostic uncertainty translates into therapeutic uncertainty regarding the choice of adjuvant or palliative chemotherapy, which may impact patient survival if treatment is inappropriate. Analysis of pancreaticoduodenectomies performed for dCCA or upfront resectable PDAC at Bordeaux University Hospital between 2018 and 2023, in the era of modern chemotherapy regimens, confirmed the impact of adjuvant chemotherapy on survival in PDAC patients. This finding underscores the necessity of administering tumor-type-adapted chemotherapy, and consequently of establishing a reliable histological diagnosis on operative specimens of periampullary tumors. We therefore developed, from a cohort of 20 patients operated for dCCA or PDAC with a confirmed diagnosis, a differential proteomic signature associated with a predictive model designed to classify indeterminate PB-ADCs. Taken together, this work provides a characterization of eCCA and establishes predictive models based on proteomic profiling. These models address both positive diagnosis on CS and differential diagnosis on operative specimens, with the objective of improving diagnostic accuracy and optimizing therapeutic management in patients with eCCA.
ED Sociétés, Politique, Santé Publique
Producing Knowledge through Ecological Upheaval: The Epistemic Commitments Within Applied Tropical Biology
by Margot BUZARE (Centre Emile Durkheim)
The defense will take place at 14h00 - Salle des thèses Campus Victoire, 3ter Place de la Victoire, 33000 Bordeaux
in front of the jury composed of
- Éric MACE - Professeur des universités - Université de Bordeaux - Directeur de these
- Céline GRANJOU - Directrice de recherche - Inrae - Rapporteur
- David DUMOULIN KERVRAN - Professeur des universités - Université Sorbonne Nouvelle - Rapporteur
- Morgan JOUVENET - Directeur de recherche - CNRS - Examinateur
- Mina KLEICHE-DRAY - Directrice de recherche - IRD - Examinateur
- Olivier COUSIN - Professeur des universités - Université de Bordeaux - Examinateur
This doctoral dissertation analyzes the production of knowledge both within and about environmental change, understood simultaneously as a social problem and a material phenomenon. Based on a study of the French agricultural research and international cooperation organization CIRAD, this work focuses on genetics and plant breeding, particularly in relation to tropical crops. Historically, this field of research has occupied an ambivalent position with regard to environmental change: since the eighteenth century and throughout the colonial era, it has both contributed to the acceleration of environmental transformations and produced knowledge about their causes and effects. This dissertation addresses the following question: how do environmental changes affect a field historically shaped by territorialized, applied, and industrial logics, and increasingly confronted with social, political, and environmental criticism? To answer this question, the study examines how scientists either redirect or maintain their research objects, field sites, and professional networks, as well as the justifications they provide to others—and to themselves—to sustain the meaning of their work at a time when ecological constraints are reshaping the criteria of scientific credibility. Drawing on a processual sociology of science, this dissertation is based on laboratory ethnography. The empirical material combines institutional archives with ethnographic fieldwork conducted between 2022 and 2024, including participant observation and interviews with 71 members of the organization. Through a socio-historical analysis of CIRAD, the dissertation shows how the rise of sustainable development frameworks since the late 1980s has provided this research area with new opportunities to strengthen its scientific legitimacy. At the laboratory level, the study describes several strategies developed by biologists to reconcile conflicting imperatives: conducting globalized genetic research in support of productivist objectives, while also producing territorialized research in the Global South that responds to social demands and incorporates environmental concerns. Finally, the analysis of practices and individual trajectories leads to the identification of four forms of environmental “epistemic commitment.” This typology makes it possible to examine both struggles for scientific credibility and the personal value conflicts experienced by researchers.