Observational Study
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Endosc. Jun 16, 2022; 14(6): 402-415
Published online Jun 16, 2022. doi: 10.4253/wjge.v14.i6.402
Role of endoscopic ultrasound and cyst fluid tumor markers in diagnosis of pancreatic cystic lesions
Hussein Hassan Okasha, Abeer Abdellatef, Shaimaa Elkholy, Mohamad-Sherif Mogawer, Ayman Yosry, Magdy Elserafy, Eman Medhat, Hanaa Khalaf, Magdy Fouad, Tamer Elbaz, Ahmed Ramadan, Mervat E Behiry, Kerolis Y William, Ghada Habib, Mona Kaddah, Haitham Abdel-Hamid, Amr Abou-Elmagd, Ahmed Galal, Wael A Abbas, Ahmed Youssef Altonbary, Mahmoud El-Ansary, Aml E Abdou, Hani Haggag, Tarek Ali Abdellah, Mohamed A Elfeki, Heba Ahmed Faheem, Hani M Khattab, Mervat El-Ansary, Safia Beshir, Mohamed El-Nady
Hussein Hassan Okasha, Abeer Abdellatef, Shaimaa Elkholy, Mohamad-Sherif Mogawer, Kerolis Y William, Hani Haggag, Mohamed El-Nady, Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, Cairo 11451, Egypt
Ayman Yosry, Magdy Elserafy, Eman Medhat, Tamer Elbaz, Ahmed Ramadan, Ghada Habib, Mona Kaddah, Department of Endemic Diseases, Cairo University, Cairo 11451, Egypt
Hanaa Khalaf, Magdy Fouad, Haitham Abdel-Hamid, Department of Tropical Medicine and Gastroenterology, Minia University, Minia 61511, Egypt
Mervat E Behiry, Department of Internal Medicine, Kasr Al-Aini Hospitals, Cairo University, Cairo 11562, Egypt
Amr Abou-Elmagd, Department of Gastroenterology, Armed forces College of Medicine, Cairo 11451, Egypt
Ahmed Galal, Endoscopy and Internal Medicine Consultant at Dr/Ahmed Galal Endoscopy Center, Alexandria 35516, Egypt
Wael A Abbas, Department of Internal Medicine, Faculty of Medicine, Assuit University, Assuit 71111, Egypt
Ahmed Youssef Altonbary, Department of Gastroenterology and Hepatology, Mansoura University, Mansoura 35511, Egypt
Mahmoud El-Ansary, Department of Gastroenterology and Hepatology, Theodor Bilharz Research Institute, Cairo 11451, Egypt
Aml E Abdou, Department of Microbiology and Immunology, Faculty of Medicine for girls Al-Azhar University, Cairo 11451, Egypt
Tarek Ali Abdellah, Heba Ahmed Faheem, Department of Internal Medicine, Faculty of Medicine, Ain shams University, Cairo 11451, Egypt
Mohamed A Elfeki, Department of Internal Medicine, Bani-suef University, Bani-suef, Bani-suef 62511, Egypt
Hani M Khattab, Department of Pathology, Faculty of Medicine, Cairo University, Cairo 11451, Egypt
Mervat El-Ansary, Department of Clinical Pathology, Faculty of Medicine, Cairo University, Cairo 11451, Egypt
Safia Beshir, Department of Environmental Medicine & Clinical Pathology, National Research Centre, Cairo 11451, Egypt
Author contributions: El-Nady M, Abeer Awad, Shaimaa El-Kholy, and Abdel-Hamid H were involved equally in writing the manuscript; Elbaz T, Ramadan A, Behiry ME, Y William K, Habib G, Kaddah M, Abou-ElMagd A, Abbas WA, Altonbary AY, El-Ansary M, Abdou AE, Haggag H, Abdellah TA, Elfeki MA, and Faheem HA were involved equally in collecting the data; Mogawer MS, Yosry A, Elserafy M, Medhat E, Khalaf H, Fouad M, Ahmed M Shalaby, Galal A, Khattab HM, El-Ansary M, and Beshir S were involved equally in reading and revising the manuscript; Okasha HH revised and approved the final manuscript; all authors have read and approved the final manuscript.
Institutional review board statement: Our institution’s Research Ethical Committee approved the study, and all patients gave their informed written consent before inclusion in the study, according to the ethical guidelines of the 1975 Declaration of Helsinki.
Conflict-of-interest statement: No conflict of interest exists.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Abeer Abdellatef, MD, Lecturer, Department of Internal Medicine and Hepatogastroenterology, Kasr Al-Aini Hospitals, Cairo University, Kasr Al-Aini Hospitals, Cairo University, PO 11451, Kasr Al-Aini Street, Cairo 11451, Egypt. beero4a@yahoo.com
Received: October 22, 2021
Peer-review started: October 22, 2021
First decision: November 15, 2021
Revised: November 28, 2021
Accepted: May 5, 2022
Article in press: May 5, 2022
Published online: June 16, 2022
Processing time: 233 Days and 11.4 Hours
ARTICLE HIGHLIGHTS
Research background

Nowadays, the awareness of pancreatic cystic lesions has become an essential issue, especially with the increased incidence of asymptomatic pancreatic cysts in the general population. Therefore, the proper diagnosis, meticulous differentiation, and staging of these pancreatic cystic lesions (PCLs) are crucial for proper management and avoiding unnecessary treatment of benign lesions and missing early treatment of the malignant/pre-malignant lesions. Endoscopic ultrasound (EUS) examination of cyst morphology with cytopathological and chemical analysis and cyst fluid analysis could improve the diagnostic capability. Also, many developed markers are valuable for predicting a malignant pancreatic cyst.

Research motivation

EUS examination of cyst morphology with cytopathological and chemical analysis and cyst fluid analysis could improve the differentiation between malignant and benign pancreatic cysts. Also, carcinoembryonic antigen (CEA), glucose, and the serine protease inhibitor Kazal-type 1 (SPINK1) are valuable markers for predicting a malignant pancreatic cyst.

Research objectives

To evaluate the role of cyst fluid analysis of different tumor markers such as cancer antigens (e.g., CA19-9 and CA72-4), carcinoembryonic antigen (CEA), SPINK1, interleukin 1 beta (IL-1β), vascular endothelial growth factor A (VEGF-A), prostaglandin E2 (PGE2), amylase, and mucin stain in diagnosing pancreatic cysts and differentiating malignant from benign lesions.

Research methods

This study included 76 patients diagnosed with PCLs using different imaging modalities. All patients underwent EUS and EUS-FNA for characterization and sampling of different PCLs.

Research results

The mean age of studied patients was 47.4 ± 11.4 years, with a slight female predominance (59.2%). Mucin stain showed high statistical significance in predicting malignancy with a sensitivity of 87.1% and specificity of 95.56%. It also showed a positive predictive value and negative predictive value of 93.1% and 91.49%, respectively (P < 0.001). We found that positive mucin stain, cyst fluid glucose, SPINK1, amylase, and CEA levels had high statistical significance (P < 0.0001). In contrast, IL-1β, CA 72-4, VEGF-A, VEGFR2, and PGE2 did not show any statistical significance. Univariate regression analysis for prediction of malignancy in PCLs showed a statistically significant positive correlation with mural nodules, lymph nodes, cyst diameter, mucin stain, and cyst fluid CEA. Meanwhile, logistic multivariable regression analysis proved that mural nodules, mucin stain, and SPINK1 were independent predictors of malignancy in PCLs.

Research conclusions

EUS examination of cyst morphology with cytopathological analysis and cyst fluid analysis could improve the differentiation between malignant and benign pancreatic cysts. Also, CEA, glucose, and SPINK1 could be used as promising markers to predict malignant pancreatic cysts.

Research perspectives

Further studies addressing new markers are recommended, which will provide a panel of laboratory data to recognize the malignant and potentially malignant lesions to establish a standard protocol for diagnosis and management. Also, cyst fluid DNA is considered a potential diagnostic agent with particular possible use in differentiating between benign and malignant cysts. Further investigation regarding this biomarker is recommended.