Year 2021 / Volume 113 / Number 10
Review
Current clinical and research fluid biomarkers to aid risk stratification of pancreatic cystic lesions

714-720

DOI: 10.17235/reed.2021.7948/2021

Ana García García de Paredes, Ferga Claudine Gleeson, Elizabeth Rajan, Enrique Vázquez-Sequeiros,

Abstract
Pancreatic cystic lesions (PCL) are composed of a heterogeneous group of entities that are increasingly diagnosed, generally as incidental findings in asymptomatic patients. In conjunction with this growing incidence, the potential for malignant transformation of mucin-producing cysts makes PCL a challenging clinical conundrum for the clinician, patient, and healthcare system. Cyst characterization based on morphology is often difficult and inaccurate. Therefore, several intracystic fluid biomarkers have been evaluated as ancillary testing to enhance the difficult balance between sparing a patient from an unnecessary high-risk pancreatic surgery and missing the opportunity to prevent or diagnose pancreatic adenocarcinoma at an early disease stage. There are two questions that are key to guide the care of patients with PCL: 1) is it a non-mucinous cyst that does not require any follow-up? and 2) if mucinous, does the cyst harbor advanced neoplasia (high-grade dysplasia or invasive carcinoma) that requires surgical resection, or is it a low-risk lesion that will benefit from a surveillance program? The purpose of this review is to give a general and practical overview of the different cyst fluid biomarkers that have been studied to address these specific questions, from classic biochemical markers such as carcinoembryonic antigen to novel genetic and epigenetic markers such as microRNA or intracystic bacterial DNA.
Share Button
New comment
Comments
No comments for this article
References
1. Zerboni G, Signoretti M, Crippa S, et al. Systematic review and meta-analysis: Prevalence of incidentally detected pancreatic cystic lesions in asymptomatic individuals. Pancreatology 2019;19:2-9.
2. European Study Group on Cystic Tumours of the P. European evidence-based guidelines on pancreatic cystic neoplasms. Gut 2018;67:789-804.
3. Choi SH, Park SH, Kim KW, et al. Progression of Unresected Intraductal Papillary Mucinous Neoplasms of the Pancreas to Cancer: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2017;15:1509-20 e4.
4. Springer S, Masica DL, Dal Molin M, et al. A multimodality test to guide the management of patients with a pancreatic cyst. Sci Transl Med 2019;11 (501):eaav4772. doi: 10.1126/scitranslmed.aav4772
5. Tanaka M, Heckler M, Liu B, et al. Cytologic Analysis of Pancreatic Juice Increases Specificity of Detection of Malignant IPMN-A Systematic Review. Clin Gastroenterol Hepatol 2019;17:2199-211 e21.
6. Brugge WR, Lewandrowski K, Lee-Lewandrowski E, et al. Diagnosis of pancreatic cystic neoplasms: a report of the cooperative pancreatic cyst study. Gastroenterology 2004;126:1330-6.
7. Faias S, Cravo MM, Chaves P, et al. A comparative analysis of glucose and carcinoembryonic antigen in diagnosis of pancreatic mucinous cysts: a systematic review and meta-analysis. Gastrointest Endosc 2021. Published Online First: 25 January 2021 Online ahead of print.
8. van der Waaij LA, van Dullemen HM, Porte RJ. Cyst fluid analysis in the differential diagnosis of pancreatic cystic lesions: a pooled analysis. Gastrointest Endosc 2005;62:383-9.
9. Simons-Linares CR, Yadav D, Lopez R, et al. The utility of intracystic glucose levels in differentiating mucinous from non-mucinous pancreatic cysts. Pancreatology 2020;20:1386-92.
10. Zikos T, Pham K, Bowen R, et al. Cyst Fluid Glucose is Rapidly Feasible and Accurate in Diagnosing Mucinous Pancreatic Cysts. Am J Gastroenterol 2015;110:909-14.
11. Faias S, Pereira L, Roque R, et al. Excellent Accuracy of Glucose Level in Cystic Fluid for Diagnosis of Pancreatic Mucinous Cysts. Dig Dis Sci 2020;65:2071-8.
12. Stigliano S, Zaccari P, Severi C. Pancreatic intra-cystic CA 19-9 dosage in the management of pancreatic cysts: Useful or confounding? Dig Liver Dis 2021;53:131-3. doi.org/10.1016/j.dld.2020.10.031
13. Maker AV, Katabi N, Qin LX, et al. Cyst fluid interleukin-1beta (IL1beta) levels predict the risk of carcinoma in intraductal papillary mucinous neoplasms of the pancreas. Clin Cancer Res 2011;17:1502-8.
14. Gaiser RA, Halimi A, Alkharaan H, et al. Enrichment of oral microbiota in early cystic precursors to invasive pancreatic cancer. Gut 2019;68:2186-94.
15. Maker AV, Hu V, Kadkol SS, et al. Cyst Fluid Biosignature to Predict Intraductal Papillary Mucinous Neoplasms of the Pancreas with High Malignant Potential. J Am Coll Surg 2019;228:721-9.
16. Maker AV, Katabi N, Gonen M, et al. Pancreatic cyst fluid and serum mucin levels predict dysplasia in intraductal papillary mucinous neoplasms of the pancreas. Ann Surg Oncol 2011;18:199-206.
17. Morris-Stiff G, Lentz G, Chalikonda S, et al. Pancreatic cyst aspiration analysis for cystic neoplasms: mucin or carcinoembryonic antigen--which is better? Surgery 2010;148:638-44; discussion 44-5.
18. Mensah ET, Smyrk T, Zhang L, et al. Cyclooxygenase-2 and Cytosolic Phospholipase A2 Are Overexpressed in Mucinous Pancreatic Cysts. Clin Transl Gastroenterol 2019;10:e00028.
19. Yip-Schneider MT, Carr RA, Wu H, et al. Prostaglandin E2: A Pancreatic Fluid Biomarker of Intraductal Papillary Mucinous Neoplasm Dysplasia. J Am Coll Surg 2017;225:481-7.
20. Faias S, Pereira L, Luis A, et al. KRAS in Cyst Fluid Obtained by Endoscopic Ultrasound-Fine-Needle Aspiration in Pancreatic Cystic Lesions: A Systematic Review and Meta-analysis. Pancreas 2019;48:749-58.
21. Singhi AD, McGrath K, Brand RE, et al. Preoperative next-generation sequencing of pancreatic cyst fluid is highly accurate in cyst classification and detection of advanced neoplasia. Gut 2018;67:2131-41.
22. Khalid A, Zahid M, Finkelstein SD, et al. Pancreatic cyst fluid DNA analysis in evaluating pancreatic cysts: a report of the PANDA study. Gastrointest Endosc 2009;69:1095-102.
23. Hata T, Dal Molin M, Suenaga M, et al. Cyst Fluid Telomerase Activity Predicts the Histologic Grade of Cystic Neoplasms of the Pancreas. Clin Cancer Res 2016;22:5141-51.
24. Majumder S, Taylor WR, Yab TC, et al. Novel Methylated DNA Markers Discriminate Advanced Neoplasia in Pancreatic Cysts: Marker Discovery, Tissue Validation, and Cyst Fluid Testing. Am J Gastroenterol 2019;114:1539-49.
25. Utomo WK, Looijenga LH, Bruno MJ, et al. A MicroRNA Panel in Pancreatic Cyst Fluid for the Risk Stratification of Pancreatic Cysts in a Prospective Cohort. Mol Ther Nucleic Acids 2016;5:e350.
Related articles

Review

New non-invasive biomarkers for colorectal cancer screening

DOI: 10.17235/reed.2020.7233/2020

Letter

Giant pancreatic cystic lymphangioma

DOI: 10.17235/reed.2020.7003/2020

Digestive Diseases Image

Pancreatic enzyme replacement for refractory multiple large pancreatic cysts

DOI: 10.17235/reed.2019.6030/2018

Editorial

Cyst wall brushing. Exploring the limits of cytology

DOI: 10.17235/reed.2018.5771/2018

Citation tools
García García de Paredes A, Gleeson F, Rajan E, Vázquez-Sequeiros E. Current clinical and research fluid biomarkers to aid risk stratification of pancreatic cystic lesions. 7948/2021


Download to a citation manager

Download the citation for this article by clicking on one of the following citation managers:

Metrics
This article has received 1546 visits.
This article has been downloaded 324 times.

Statistics from Dimensions


Statistics from Plum Analytics

Publication history

Received: 07/03/2021

Accepted: 25/04/2021

Online First: 05/05/2021

Published: 06/10/2021

Article revision time: 26 days

Article Online First time: 59 days

Article editing time: 213 days


Share
This article has been rated by 7 readers.
Reader rating:
Valora este artículo:




Asociación Española de Ecografía Digestiva Sociedad Española de Endoscopia Digestiva Sociedad Española de Patología Digestiva
The Spanish Journal of Gastroenterology is the official organ of the Sociedad Española de Patología Digestiva, the Sociedad Española de Endoscopia Digestiva and the Asociación Española de Ecografía Digestiva
Cookie policy Privacy Policy Legal Notice © Copyright 2023 y Creative Commons. The Spanish Journal of Gastroenterology