This Technical and Technology Review from the European Society of Gastrointestinal Endoscopy (ESGE) represents an update of the previous document on the technical aspects of endoscopic ultrasound (EUS)-guided sampling in gastroenterology, including the available types of needle, technical aspects of tissue sampling, new devices, and specimen handling and processing. Among the most important new recommendations are:ESGE recommends end-cutting fine-needle biopsy (FNB) needles over reverse-bevel FNB or fine-needle aspiration (FNA) needles for tissue sampling of solid pancreatic lesions; FNA may still have a role when rapid on-site evaluation (ROSE) is available.ESGE recommends EUS-FNB or mucosal incision-assisted biopsy (MIAB) equally for tissue sampling of subepithelial lesions ≥20 mm in size. MIAB could represent the first choice for smaller lesions (<20 mm) if proper expertise is available.ESGE does not recommend the use of antibiotic prophylaxis before EUS-guided tissue sampling of solid masses and EUS-FNA of pancreatic cystic lesions.

Now that tissue cores can be obtained using fine-needle biopsy (FNB) needles, the ways tissues are handled for endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) are changing. Direct smear, touch smear of core tissues, and centrifugation have been used for cytological examinations, and liquid-based cytology (LBC), which allows immunostaining and genetic tests that use residual samples, is emerging as an alternative. We emphasize that liquid cytology (Cytospin™ cytology and LBC) is still important, because it enables the diagnosis of pancreatic ductal adenocarcinoma (PDAC) when cancerous cells are scarce in specimens. Cell blocks are being replaced by core tissues obtained via FNB needles. Recent reports indicate that rapid on-site evaluation (ROSE) is not necessary when FNB needles are used, and macroscopic on-site evaluation is used to evaluate specimen adequacy. Macroscopic findings of specimens are helpful in the diagnostic workup and for clarifying specimen-handling methods. In addition to the red strings and white cores observed in PDAC, mixed red and white strings, gray tissues, and gelatinous tissues are observed. Gray (necrotic) tissues and gelatinous (mucus) tissues are more suitable than histology for cell block or cytological processing. Tumor cells in neuroendocrine tumors (NETs) are numerous in red strings but cannot be observed macroscopically. ROSE might thus be necessary for lesions that may be NETs. Core tissues can be used for genetic tests, such as those used for KRAS mutations and comprehensive genomic profiling. Cytological materials, including slides and LBC specimens, can also be genetic test materials.

The impact of KRAS mutation testing on pancreatic ductal adenocarcinoma (PDAC) samples by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for reducing the need to repeat EUS-FNA has been demonstrated. Such testing however is not part of standard practice for endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB).

We aim to analyse the proportion of non-contributive samples by EUS-FNB and to evaluate the impact of KRAS mutation testing on the diagnosis, theranostics and survival.

In this retrospective study, the impact on diagnosis and survival of KRAS testing for contributive and non-contributive samples by EUS-FNB was analysed.

The EUS-FNB samples, combined with KRAS testing using the Idylla® technique on liquid-based cytology from patients with PDAC between February 2019 and May 2023, were retrospectively reviewed. The cytology results were classified according to the guidelines of the World Health Organization System for Reporting Pancreaticobiliary Cytopathology (WHOSRPC).

A total of 85 EUS-FNB specimens were reviewed. In all, 25 EUS-FNB samples did not lead to a formal diagnosis of PDAC according to the WHOSRPC (30.2%). Out of these 25, 11 (44%) could have been considered positive for a PDAC diagnosis thanks to the KRAS mutation test without carrying out further diagnosis procedures. The sensitivity of KRAS mutation testing using the Idylla technique was 98.6%. According to the available data, survival rates were not statistically different depending on the type of mutation.

KRAS mutation testing on liquid-based cytology using the Idylla or equivalent technique, combined with the PDAC EUS-FNB sample, should become a standard for diagnosis to avoid delaying treatment by doing another biopsy. Furthermore, knowledge of the KRAS status from treatment initiation could be used to isolate mutations requiring targeted treatments or inclusion in clinical research trials, especially for wild-type KRAS PDAC.