Aim of our study was to evaluate the feasibility of generating patient-derived organoids (PDOs) from EUS-TA samples

Prospective study of patients referred to the Endoscopy Unit of the University Hospital of Santiago de Compostela, Spain, for EUS-TA of pancreatic tumour. EUS was performed using linear echoendoscopes and Hitachi-Fujifilm systems. Tissue sampling was performed using core needles. Tissue samples were minced and dissociated into small pieces from which cell cultures were established using growth medium supplemented with factors such as gastrin, respondin-1, noggin and WNT-3A proteins, which play a key role in the self-renewal and maintenance of human pancreatic PDOs. Data are presented as mean ± standard deviation, or median and range for quantitative variables and as percentages for categorical variables. Factors associated with the success in obtaining PDOs were evaluated using multivariate logistic regression, with location, staging, lesion size, needle size and number of passes considered as independent variables. 

The study included 28 patients diagnosed with PDCA (mean age 73.3 ± 10.1 years, 14 males). Mean tumour size was 41.8 ± 15.1 mm; 13 lesions were located in the head, 9 in the body, 5 in the tail and 1 in the uncinate process. One PDAC (3.6%) was considered resectable, 5 (17.9%) borderline, 6 (21.4%) locally advanced and 16 (57.1%) metastatic at the time of diagnosis. For EUS-TA, 19-gauge and 25-gauge needles were used in 1 case (3.6%) each, and a 22-gauge needle was used in the remaining cases (26 cases, 92.9%). A median of two passes (range 1-4) were performed. In an initial training set, PDOs were obtained in 1 of 12 (8.3%) samples. After protocol refinement, the success rate of PDO establishment increased to 56.3% (9 of 16 patients). On multivariate analysis, neither lesion location, stage, lesion size, needle size, nor number of passes were associated with PDO success.

This study highlights the feasibility of obtaining PDOs from EUS-TA of PDAC patients. The protocols developed in this study allowed the establishment of pancreatic PDOs from a minimal tissue source, providing a valuable tool for further functional modelling of human pancreatic tumours.