Pancreatic Organoids establishment from EUS Fine Needle Biopsy in patients affected by Pancreatic Cancer: Preliminary results from the Bile Biopsy study

Aims We performed a prospective observational study aiming to evaluate the feasibility to create tridimensional pancreatic derives organois (PDOs) from EUS guided FNB samples of patients affected by PDAC and to correlate patients derived organoids (PDOs) with native cancer histology. The secondary endpoint of our study was to assess the feasibility of using bile as biological fluid for cell free DNA (cfDNA) and to investigate the landscape of cfDNA in bile and plasma of patients affected by PDAC.

Methods Patients with strong suspicion or recent diagnosis of PDAC and concomitant jaundice were prospectively evaluated. Every patient underwent EUS guided FNB for histological diagnosis and organoid collection was performed. By the time of biliary drainage, bile and plasma were collected for DNA extraction and analysis (Fig. 1, Research Workflow).

Results From June 2023 to September 2023, thirty-six patients with neoplastic jaundice were evaluated. Eighteen patients with final diagnosis of PDAC have been included in the study. Eighteen of them underwent biliary drainage with collection of bile and plasma. Sixteen of them underwent EUS guided FNB for organoid collection. Baseline characteristics are described in Table 1. Mean tumor size was 33.7±9.6 mm. Tumor was located in the head of pancreas in 94.4% of cases. Nine patients (50%) were metastatic by the time of diagnosis, eight patients (44%) had locally advanced disease and only one patient was considered resectable. EUS guided tissue acquisition was performed sing FNB needles (Table 2). PDOs establishment rate was successful in 100% of cases. No EUS-FNB related adverse events were observed. Organoids self-renewal and self-organization are shown in Figure 2. At a quality concordance pathological analysis between PDAC and PDOs, morphological similarities have been observed in all cases (100%). Cellular morphology and nuclei atypia were the most consistent similarities. Organoids showed a glandular over expression compared to native PDAC (Fig 3). Extracted cfDNA was significantly higher in bile supernatant than in plasma (2.9 ng/ml vs 19.8 ng/ml p=0.0001) (Fig 4). No significant differences were found for plasma and bile cfDNA among disease stages. Higher level of bile cfDNA in locally advanced disease and a trend of higher level of plasma cfDNA in metastatic stage. Bile cfDNA showed longer DNA fragment compared to plasma

Conclusions Organoids establishment is feasible and safe with a single passage of EUS guided FNB. PDOs maintain the morphological architecture of native cancer, although the absence of dense stromal reaction leads to a remarkable organoids ability to create glandular structures. Qualitative and quantitative composition of ctDNA is superior in bile rather than in plasma, making this fluid an important tool for NGS analysis and a better comprehension of tumor mutations

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Artikel online veröffentlicht:
15. April 2024