Endoscopic ultrasound-guided biopsies vs surgical specimens for establishing patient-derived pancreatic cancer organoids: A systematic review and meta-analysis.

BACKGROUND AND AIMS: Patient-Derived Tumor Organoids (PDTOs) is a promising new disease model in pancreatic cancer for use in personalized medicine, but overall success rate (SR) of establishing these cultures from endoscopic ultrasound-guided biopsies is unknown. METHODS: We searched relevant databases publications reporting SR of PDTO establishment from pancreatic cancer. The primary outcome was SR stratified on tissue acquisition method (EUS-guided biopsies, percutaneous biopsies, and surgical specimens). RESULTS: We identified 24 studies including 1,053 attempts at establishing PDTOs. Overall SR was 63% (95% CI: 54%-72%). Pooled SR of PDTO establishment from EUS-guided biopsies, percutaneous biopsies, and surgical specimens were 60% (95% CI: 43-76%), 36% (95% CI: 14-61%) and 62% (95% CI: 48-75%), respectively and did not differ significantly (p = 0.1975). CONCLUSION: The SR of PDTO establishment from EUS-guided biopsies is comparable to surgical specimens. Both techniques are suitable for tissue acquisition for PDTOs in clinical and research settings.

Validation of a Novel EUS-FNB-Derived Organoid Co-Culture System for Drug Screening in Patients with Pancreatic Cancer.

Cancer-associated fibroblasts (CAFs) have been shown to impact the chemosensitivity of patient-derived tumor organoids (PDTOs). However, the published literature comparing PDTO response to clinical outcome does not include CAFs in the models. Here, a co-culture model was created using PDTOs and CAFs derived from endoscopic ultrasound-guided fine-needle biopsies (EUS-FNBs) for potential use in drug screening applications. Co-cultures were established, and growth was compared to monocultures using image metrics and a commercially available assay. We were able to establish and expand validated malignant PDTOs from 19.2% of adenocarcinomas from EUS-FNBs. CAFs could be established from 25% of the samples. The viability of PDTOs in the mixed cell co-culture could be isolated using image metrics. The addition of CAFs promoted PDTO growth in half of the established co-cultures. These results show that co-cultures can be established from tiny amounts of tissue provided by EUS-FNB. An increased growth of PDTOs was shown in co-cultures, suggesting that the present setup successfully models CAF-PDTO interaction. Furthermore, we demonstrated that standard validation techniques may be insufficient to detect contamination with normal cells in PDTO cultures established from primary tumor core biopsies.