Thibaut Waeckel

Le carcinome rénal à cellules claires (CCRcc) représente la forme la plus fréquente et la plus agressive des cancers du rein. Sa biologie est dominée par l'inactivation du gène suppresseur de tumeur VHL et l'accumulation des facteurs de transcription HIF-1α et HIF-2α, qui orchestrent l'adaptation hypoxique tumorale. La voie Hippo, dont les effecteurs principaux sont YAP-1 et TAZ, émerge comme un acteur majeur de l'oncogenèse rénale, notamment via une interrelation fonctionnelle complexe avec la voie VHL/HIF.Ce travail de thèse, poursuit trois axes complémentaires. Le premier axe porte sur l'analyse de la valeur théranostique de YAP-1, HIF-1α et HIF-2α en tant que biomarqueurs via une analyse en immunohistochimie effectuée dans une cohorte de 150 patients atteints de CCRcc dont 75 métastatiques. Les résultats suggèrent que la co-expression nucléaire YAP-1/HIF-1α est associée à une meilleure réponse aux inhibiteurs de tyrosine kinase en situation métastatique. Le second axe concerne le développement du projet OrgaCCR - UroCCR-185, qui établit la faisabilité de la culture d'organoïdes de CCRcc à partir de tumeurs fraîches de patients opérés. Le troisième axe présente le modèle ExplanCCR, une plateforme d'explants tumoraux afin de pouvoir tester les principales thérapeutiques du CCRcc en moins d'une semaine, à faible coût et avec préservation de l'architecture tissulaire native. Enfin, les perspectives du projet Chimiogramme-CCRcc sur membrane chorio-allantoïque (CAM) sont présentées comme un modèle complémentaire intégrant la vascularisation tumorale.L'ensemble de ces travaux illustre une vision cohérente de la recherche translationnelle en oncologie rénale, articulant recherche biologique, validation clinique et développement d'outils précliniques de précision au sein du réseau national UroCCR.

Objective: The aim of this study was to evaluate the diagnostic yield and downstream clinical impact of routine preoperative chest CT in patients undergoing partial nephrectomy (PN) for localized renal cell carcinoma. Methods: We conducted a retrospective multicentre study using data from the French Urological Cancer Comprehensive Cohort (UroCCR) registry. Adult patients who underwent PN for localized renal masses between 2010 and 2024 and had preoperative chest CT within 30 days before surgery were included. The primary endpoint was the detection rate of synchronous pulmonary metastases. Secondary endpoints included characteristics of metachronous metastases and diagnostic or scheduling consequences of preoperative imaging. Results: Among 7351 patients, 6679 underwent surgery and 5016 had a preoperative chest CT. Of these, 4483 (89.4%) had clinical T1 tumours. Synchronous pulmonary metastases were identified in only 17 patients (0.38%), all with larger or higher grade tumours. These patients had significantly higher rates of positive surgical margins (17.6% vs. 6.1%, p = 0.04), but no significant difference in age, sex or comorbidity profile. Among 6075 patients with postoperative follow‐up, 191 (3.14%) developed metachronous pulmonary metastases. Of these, 14 (7.3%) had a previously negative preoperative CT, with a median time to progression of 52.6 months. Importantly, 166 (3.7%) patients underwent additional, ultimately non‐contributive thoracic investigations, and 2.1% experienced surgical delays due to incidental or equivocal CT findings. Conclusions: The diagnostic yield of routine preoperative chest CT in patients with clinical T1 RCC is exceedingly low (<0.5%). These data support the omission of routine chest CT in asymptomatic, low‐risk cT1 RCC, potentially sparing over 95% of patients from unnecessary imaging, additional tests and surgical delays. A risk‐adapted, symptom‐guided strategy may optimize patient care while reducing radiation exposure and healthcare costs.

Objectives : Partial nephrectomy can lead to complications such as urinary fistulas, with an incidence ranging from 1 to 17%. Currently, there are no formal guidelines for managing these urinary fistulas. The aim of this study is to assess the time to fistula resolution according to different treatment options. Materials and Methods: The U-Leak study is a retrospective, observational, and multicenter French cohort based on analyses from the UroCCR database. The inclusion period extends from 2009 to 2024, included patients who underwent partial nephrectomy with post-operative urinary fistula. We identified two groups: patients managed interventionally and patients managed without any drainage. The primary objective was to evaluate the time to resolution of urinary fistulas after partial nephrectomy. Results: We included 127 patients, predominantly male (71.7%), with a mean age of 59.4 years. The majority of partial nephrectomies (55.2%) were performed via transperitoneal robotic surgery. Interventional management was applied to 82.4% of patients, 39.5% received a primary double J stent, 17.7% of patients were treated with a bladder catheter combined with a double J and 25.2% received percutaneous drain, bladder catheter or association of two or three treatment. Twenty- five patients required a second intervention. The median time to fistula resolution was 43 days [13.5–81.5] after the first treatment and 48 days [21.5–67.5] after the second. Overall, 79.8% of fistulas resolved after the first intervention. The median time to resolution was 44 days [29.0–69.5] without interventional treatment and 50 days [23.5–87.0] with treatment, with no statistically significant difference between the two groups (p = 0.432). Conclusion: We did not observe a significant difference in the time to resolution of urinary fistulas after partial nephrectomy between patients managed interventionally and those managed without any drainage.

Black patients in France exhibit a higher prevalence of non–clear cell renal cell carcinoma subtypes and are diagnosed at younger ages with earlier‐stage tumors. These patterns, along with distinct transcriptomic profiles in nonneoplastic renal tissue, support ancestry‐informed approaches to renal cell carcinoma diagnosis and research.

Background Surgical pyelonephritis (SP) encompasses severe upper urinary tract infections, including pyonephrosis, renal and perinephric abscesses, and emphysematous pyelonephritis. The 2024 EAU Guidelines classify these as complicated UTIs requiring early antibiotic therapy, hemodynamic stabilization, and prompt source control. This study aimed to reassess the role of emergency nephrectomy (EN) in SP management and to identify predictors of conservative management (CM) failure. Methods We conducted a retrospective, single-center study including patients treated for SP at Caen University Hospital, France, between January 2011 and December 2022. Results Eighty-eight patients were included: 10 underwent primary EN, and 78 received CM, of whom 9 (11.5%) later required secondary nephrectomy (SN) due to CM failure. Renal abscesses (RA) were the most frequent indication for EN, followed by emphysematous pyelonephritis. Diabetes was significantly more prevalent in EN patients (p < 0.001). Urinary tract obstruction was observed in 30.0% of EN patients versus 82.1% of those initially treated conservatively (p = 0.001). Initial EN patients had higher severe morbidity rates than CM patients (50.0% vs. 29.5%, p = 0.04), although similar to SN patients (66.7% vs. 50.0%, p = 0.07). A high ASA score, chronic kidney disease (CKD), and smoking were associated with an increased risk of CM failure. Conclusions Surgical pyelonephritis should be managed stepwise, favoring conservative approaches when possible. Early identification of patients at risk of failure is crucial, and timely escalation to nephrectomy may improve outcomes. Biomarkers and standardized reassessment protocols may support better risk stratification.