Thèse d'exercice
Améliorer le diagnostic des lésions pancréatiques grâce à l'analyse en biologie moléculaire des ponctions-biopsies pancréatiques et de l'ADN tumoral circulant (ADIPAN)
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Introduction:
While incidence of pancreatic adenocarcinoma (PA) is increasing, the only curative treatment remains surgery, for which only 20% of patients are eligible at diagnosis. In the absence of a validated biological marker for screening, and imperfect diagnostic methods currently available, we aimed to study interest of molecular biology on CytoLyt collected during upper gastrointestinal echo-endoscopy (EUS) and on circulating tumor DNA (ctDNA) in the diagnosis of pancreatic lesions.
Method:
This ongoing prospective study began in March 2021, including patients referred to gastroenterology department of Poitiers University Hospital for EE as part of a diagnostic workup of a pancreatic lesion. For all patients, sample recovered thanks to fine needle biopsy (EUS-FNB) made during EUS benefit, in addition to the traditional anatomopathological analysis, from an analysis in molecular biology department using droplet digital PCR (ddPCR) and next-generation-sequencing (NGS) in order to highlight possible mutations within the lesion.
In addition, all patients benefit from ctDNA test in blood, both by ddPCR and NGS.
Results:
First analysis shows that our population of 84 patients is on average 53 years old, with a sex ratio close to 1. Histological analysis of the first EUS-FNB concludes in more than half of PA (n=41/78; 52.4%) while the pathological diagnosis of PA was finally done for 50/84 patients (59.5%). After a single echo-endoscopy, for 15.4% of pancreatic lesion biopsy, it was “non-diagnostic” sample (n=12/78). The first molecular biology analyses have shown that ddPCR is the only method that has been able to detect ctDNA for the moment. The study is based on pre-analytical methods of ctDNA in accordance with current recommendations. Finally, our protocol ensured the necessary amount of DNA to provide sufficient sensitivity for NGS detection on EUS-FNB, without interfering with histological analysis.
Conclusion:
Our study is therefore based on a representative population of pancreatic lesions and expertise in terms of endoscopy, anatomopathological analysis and molecular biology, to highlight the possible interest in the diagnosis of PA.
Keywords : Pancreatic adenocarcinoma, diagnostic, molecular biology, droplet digital PCR, next-generation-sequencing, circulating tumor DNA.
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