# Addressing the unmet clinical need for low-volume assays in early diagnosis of pancreatic cancer

## TL;DR

This paper addresses challenges in diagnosing pancreatic cancer through limited-volume pancreatic cyst fluid samples and proposes new methods to improve early detection and clinical decisions.

## Contribution

The paper introduces a novel approach using SERS that requires only 50 µL of cyst fluid to rule out non-mucinous cysts and supports follow-up analysis.

## Key findings

- SERS-based detection can accurately rule out non-mucinous pancreatic cysts with no malignant potential using 50 µL of fluid.
- The method leaves enough fluid for further analysis of markers to stratify dysplasia grades in mucinous cysts.
- Current limitations in clinical assays lead to inconsistent diagnoses and unnecessary surgeries.

## Abstract

The incidental detection of pancreatic cysts, an opportunity for the early detection of pancreatic cancer, is increasing, owing to an aging population and improvements in imaging technology. The classification of pancreatic cystic precursors currently relies on imaging and cyst fluid evaluations, including cytology and protein and genomic analyses. However, there are persistent limitations that obstruct the accuracy and quality of information for clinicians, including the limited volume of the complex, often acellular, and proteinaceous milieu that comprises pancreatic cyst fluid. The constraints of currently available clinical assays lead clinicians to the subjective and inconsistent application of diagnostic tools, which can contribute to unnecessary surgery and missed pancreatic cancers. Herein, we describe the pathway toward pancreatic cyst classification and diagnosis, the volume requirements for several clinically available diagnostic tools, and some analytical and diagnostic limitations for each assay. We then discuss current and future work on novel markers and methods, and how to expand the utility of clinical pancreatic cyst fluid samples. Results of ongoing studies applying SERS as a detection mode suggest that 50 µL of pancreatic cyst fluid is more than sufficient to accurately rule out non-mucinous pancreatic cysts with no malignant potential from further evaluation. This process is expected to leave sufficient fluid to analyze a follow-up, rule-in panel of markers currently in development that can stratify grades of dysplasia in mucinous pancreatic cysts and improve clinical decision-making.