Copyright: ©Author(s) 2026. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution-NonCommercial (CC BY-NC 4.0) license. No commercial re-use. See permissions. Published by Baishideng Publishing Group Inc.
Intracystic glucose is superior to carcinoembryonic antigen in diagnosing mucinous pancreatic cysts in genomic era: Systematic review and meta-analysis
Giacomo Emanuele Maria Rizzo, Giuseppe Infantino, Giovanni Marchegiani, Jorge D Machicado, Marco Del Chiaro, Ilaria Tarantino, Gemma Rossi, Paolo Giorgio Arcidiacono, Giuseppe Vanella, Lucia Guilabert, Sara Nikolić, Gabriele Capurso
Giacomo Emanuele Maria Rizzo, Giuseppe Infantino, Ilaria Tarantino, Gastroenterology and Endoscopy Unit, IRCCS-ISMETT, Palermo 90127, Sicilia, Italy
Giacomo Emanuele Maria Rizzo, Giuseppe Infantino, Ilaria Tarantino, UPMC Italy, Palermo 90127, Sicilia, Italy
Giacomo Emanuele Maria Rizzo, Gastroenterology and Digestive Endoscopy, La Maddalena Cancer Center, Palermo 90146, Sicilia, Italy
Giovanni Marchegiani, Department of Surgery, Oncology and Gastroenterology (DiSCOG), Hepato Biliary Pancreatic (HPB) and Liver Transplant Surgery, Padua University Hospital, Padova 35100, Veneto, Italy
Jorge D Machicado, Department of Gastroenterology, University of Michigan Health, Ann Arbor, MI 48107, United States
Marco Del Chiaro, Department of Surgery, University of Colorado School of Medicine, Aurora, Aurora, CO 80010, United States
Gemma Rossi, Paolo Giorgio Arcidiacono, Giuseppe Vanella, Gabriele Capurso, Division of Pancreatobiliary Endoscopy and Endosonography, Pancreas Translational & Clinical Research Center, IRCCS San Raffaele Scientific Institute, Vita-Salute San Raffaele University, Milan 20132, Lombardy, Italy
Lucia Guilabert, Department of Gastroenterology, Dr. Balmis General University Hospital, Instituto de Investigación Sani-taria y Biomédica de Alicante, Alicante 03001, Valencia, Spain
Sara Nikolić, Department of Gastroenterology, Internal Medicine Clinic, University Medical Centre Maribor, Maribor 2000, Slovenia
Co-first authors: Giacomo Emanuele Maria Rizzo and Giuseppe Infantino.
Author contributions: Rizzo GEM and Infantino G contributed to conceptualization, resources, research, writing - original draft; Rizzo GEM contributed to software; Rizzo GEM and Capurso G contributed to methodology; Rizzo GEM, Infantino G, Marchegiani G, Machicado JD, Chiaro MD, Tarantino I, Rossi G, Arcidiacono PG, Vanella G, Guilabert L, Nikolic S, and Capurso G contributed to review & editing, comments; Rizzo GEM, Marchegiani G, Machicado JD, Chiaro MD, Tarantino I, Arcidiacono PG, Vanella G, Capurso G contributed to supervision; Marchegiani G, Machicado JD, Chiaro MD, Tarantino I, Rossi G, Arcidiacono PG, Guilabert L, and Capurso G contributed to validation; Capurso G contributed to writing - original draft, research.
Conflict-of-interest statement: Giacomo Emanuele Maria Rizzo, Giuseppe Infantino, Giovanni Marchegiani, Jorge D. Machicado, Ilaria Tarantino, Gemma Rossi, Paolo Giorgio Arcidiacono, Giuseppe Vanella, Lucia Guilaber, Sara Nikolic and Gabriele Capurso have no conflict of interest to declare. Marco Del Chiaro has the following COI: Co-PI of a Boston Scientific multicenter study on the use of intra-operative pancreatoscopy in IPMN patients and recipient of a research grant from Haemonetics (INC).
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Corresponding author: Giacomo Emanuele Maria Rizzo, MD, PhD, Gastroenterology and Endoscopy Unit, IRCCS-ISMETT, UPMC Italy, Via Tricomi, 5, Palermo 90127, Sicilia, Italy.
g.rizzo.gr@gmail.com
Received: March 3, 2026
Revised: March 14, 2026
Accepted: April 20, 2026
Published online: May 24, 2026
Processing time: 78 Days and 15.1 Hours
BACKGROUND
A differential diagnosis between mucinous and non-mucinous pancreatic cysts is critical for clinical decision making, as mucinous cysts have malignant potential. While intracystic carcinoembryonic antigen (CEA) remains widely used and molecular markers hold promise, intracystic glucose (IG) has emerged as a promising, easily assessable, and economical alternative.
AIM
To investigate the diagnostic performances of IG, alone or compared to CEA.
METHODS
A systematic review and meta-analysis was conducted until April 2025. Pooled estimates of diagnostic metrics and their comparisons were calculated using a random effects model. A bivariate summary receiver operating characteristic model was used. Subgroup analyses and risks of bias assessment were also conducted.
RESULTS
Sixteen studies (1398 patients) were included. Compared with CEA, IG showed higher pooled sensitivity (95% vs 57%) and accuracy (90% vs 72%), with a lower negative likelihood ratio (LR- 0.08 vs 0.46), whereas CEA demonstrated higher specificity (97% vs 85%) and a higher positive likelihood ratio (LR+ 11 vs 6). The area under the receiver operating characteristic was 0.96 for IG and 0.82 for CEA. Pairwise analysis confirmed the superiority of IG in terms of sensitivity [odd ratio (OR): 9.36] and accuracy (OR: 3.35), while specificity favored CEA (OR: 0.43). Specificity of CEA was influenced by many factors, even by the definitive diagnostic method (histology/cytology vs other modalities, 93% vs 98%, P = 0.02).
CONCLUSION
This study reinforced the current recommendations supporting the use of IG as a first-line rule-out biomarker for mucinous pancreatic cysts due to its high sensitivity, while CEA may retain a complementary role as a rule-in test in clinical scenarios where higher specificity is required, such as surgical referral.
Core Tip: Accurate diagnosis of pancreatic cysts is fundamental for patient management. Intracystic glucose (IG), a simple and cost-effective marker, showed promising results compared to carcinoembryonic antigen (CEA) and emerging molecular markers. Nonetheless, low quality evidences and weak recommendation have been reported in the guidelines. In this study, sixteen studies showed glucose had higher accuracy [odd ratio (OR): 3.35] and sensitivity (OR: 9.36) than CEA, while CEA had greater specificity (OR: 0.43). These findings support the use of IG as a methodologically stable biomarker, particularly suitable as a rule-out test for mucinous cysts. Therefore, this study reinforces the role of IG as a first-line diagnostic biomarker in identifying mucinous pancreatic cysts. Physicians can easily use IG in identifying mucinous cysts with greater certainty.
