Mačinga P, Zahradník J, Hucl T, Janoštiak R. Bridging the intraductal papillary mucinous neoplasm risk stratification gap: A critical review of current and emerging biomarkers. World J Gastrointest Oncol 2026; 18(8): 120019 [DOI: 10.4251/wjgo.120019]
Corresponding Author of This Article
Radoslav Janoštiak, PhD, Professor, BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, Vestec 25250, Czech Republic. radoslav.janostiak@lf1.cuni.cz
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Oncology
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review-article
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Mačinga P, Zahradník J, Hucl T, Janoštiak R. Bridging the intraductal papillary mucinous neoplasm risk stratification gap: A critical review of current and emerging biomarkers. World J Gastrointest Oncol 2026; 18(8): 120019 [DOI: 10.4251/wjgo.120019]
World J Gastrointest Oncol. Aug 15, 2026; 18(8): 120019 Published online Aug 15, 2026. doi: 10.4251/wjgo.120019
Bridging the intraductal papillary mucinous neoplasm risk stratification gap: A critical review of current and emerging biomarkers
Peter Mačinga, Jiří Zahradník, Tomáš Hucl, Radoslav Janoštiak
Peter Mačinga, Tomáš Hucl, Department of Gastroenterology and Hepatology, Institute for Clinical and Experimental Medicine, Prague 14021, Czech Republic
Jiří Zahradník, Radoslav Janoštiak, BIOCEV, First Faculty of Medicine, Charles University, Vestec 25250, Czech Republic
Author contributions: Mačinga P and Janoštiak R conceived and designed the study, collected the data, drafted the manuscript, and prepared the tables; Mačinga P, Janoštiak R, Zahradník J contributed to data analysis; Zahradník J critically reviewed the manuscript for important intellectual content; Hucl T critically reviewed the manuscript and provided expert clinical input. All authors read and approved the final version of the manuscript.
Supported by Czech Health Research Council, No. NU23J-06-00043; Charles University PRIMUS Program, No. PRIMUS/22/MED/007; and European Union-Next Generation EU, Programme EXCELES, No. LX22NPO5102.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Corresponding author: Radoslav Janoštiak, PhD, Professor, BIOCEV, First Faculty of Medicine, Charles University, Průmyslová 595, Vestec 25250, Czech Republic. radoslav.janostiak@lf1.cuni.cz
Received: February 13, 2026 Revised: March 31, 2026 Accepted: April 20, 2026 Published online: August 15, 2026 Processing time: 172 Days and 2 Hours
Abstract
Intraductal papillary mucinous neoplasms (IPMNs) are the most common cystic precursor to pancreatic ductal adenocarcinoma. However, current clinical guidelines do not sufficiently distinguish indolent lesions from high-grade dysplasia or invasive carcinoma. The existing risk stratification frameworks are either sensitivity-focused (e.g., International Association of Pancreatology, European, American College of Gastroenterology) or specificity-oriented (e.g., American Gastroenterological Association). They must balance the risk of missed cancer against substantial overtreatment. Therefore, numerous diagnostic and prognostic biomarkers have been investigated, including cyst fluid carcinoembryonic antigen, cytology, next-generation sequencing panels, cytokines such as interleukin 1β and prostaglandin E2, glycoproteins such as carbohydrate antigen 19-9 and mucin 5AC, and cell-surface markers such as Das-1. Although several markers were promising in early studies, their performance has been limited by small cohorts, surgically-enriched populations, inconsistent histopathologic endpoints, frequent pooling of high-grade dysplasia and invasive carcinoma, and heterogeneous sample platforms. Few biomarkers have undergone rigorous multicenter validation or cost-effectiveness assessment, and many require technically complex workflows that limit widespread adoption. This critical review summarizes the current evidence and delineates the methodological, biological, and translational barriers that impede accurate IPMN risk stratification. We also identify key pitfalls in the biomarker literature and outline the priorities necessary to bridge the gap between early proof-of-concept studies and clinical integration into IPMN management.
Core Tip: Current guidelines for intraductal papillary mucinous neoplasm management inadequately distinguish indolent lesions from high grade dysplasia, resulting in both overtreatment and missed cancer. This evidence review critically examines established and emerging circulating and cyst fluid biomarkers, including molecular, inflammatory, and glycoprotein markers. We emphasize diagnostic performance, methodological limitations, and translational barriers. We highlight the impact of pooled histological endpoints, small surgical cohorts, assay heterogeneity, and lack of multicenter validation on the accuracy of the current studies. Finally, we outline the requirements needed to clinically integrate these biomarkers into intraductal papillary mucinous neoplasm risk stratification.
