Next-generation sequencing of pancreatic cyst wall specimens obtained using micro-forceps for improving diagnostic accuracy

Astbury, Stuart; Baskar, Aishwarya; Grove, Jane I; Kaye, Philip; Aravinthan, Aloysious Dominic; James, Martin; Clarke, Christopher; Aithal, Guruprasad P.; Venkatachalapathy, Suresh Vasan

Abstract

Background and study aims: Pancreatic cysts are common incidental findings, with an estimated prevalence of 13-15% in imaging done for other reasons. Diagnosis often relies on collection of cyst fluid, but tissue sampling using micro-forceps may allow for a more reliable diagnosis and higher yield of DNA for next-generation sequencing (NGS). The primary aim was to assess the performance of NGS in identifying mucinous cyst. The secondary aims were to assess DNA yield between the cyst fluid and cyst wall tissue, complication rate and performance of conventional investigations.

Patients and methods: 24 patients referred for endoscopic ultrasound were recruited. Biopsies were taken using micro-forceps and the AmpliSeq Cancer Hotspot panel was used for NGS, a PCR assay targeting several hotspots within 50 genes, including GNAS, KRAS and VHL.

Results: The concentration of DNA extracted from 24 cyst wall samples was significantly higher than in the 9/24 available matched cyst fluid samples. The sensitivity, specificity and diagnostic accuracy of NGS for diagnosing mucinous cyst was 93%, 50% and 84%, standard of care -66.6%, 50% and 63.1% and for standard of care with NGS was 100%, 50% and 89.4% respectively. Cyst wall biopsy was able to diagnose 19/24 cysts (4 high risk, 7 intraductal papillary mucinous neoplasm, 4 cysts of mucinous origin and 4 benign).

Conclusions: NGS data correlate well with histology and may aid in diagnosis and risk stratification of pancreatic cysts. Cyst wall biopsy performs well in diagnosing cysts but was inadequate in five of 24 patients.

Citation

Astbury, S., Baskar, A., Grove, J. I., Kaye, P., Aravinthan, A. D., James, M., …Venkatachalapathy, S. V. (2023). Next-generation sequencing of pancreatic cyst wall specimens obtained using micro-forceps for improving diagnostic accuracy. Endoscopy International Open, 11(10), E983-E991. https://doi.org/10.1055/a-2163-8805

• Journal Article Type: Article
• Acceptance Date: Jun 15, 2023
• Online Publication Date: Oct 12, 2023
• Publication Date: 2023-10
• Deposit Date: Sep 14, 2023
• Publicly Available Date: Sep 14, 2023
• Journal: Endoscopy International Open
• Print ISSN: 2364-3722
• Electronic ISSN: 2196-9736
• Publisher: Thieme Publishing
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 10
• Pages: E983-E991
• DOI: https://doi.org/10.1055/a-2163-8805
• Keywords: Pancreatobiliary (ERCP/PTCD), Tissue diagnosis, Endoscopic ultrasonography, Pancreas, Fine-needle aspiration/biopsy, GI Pathology
• Public URL: https://nottingham-repository.worktribe.com/output/24870318
• Publisher URL: https://www.thieme-connect.de/products/ejournals/abstract/10.1055/a-2163-8805