Copyright ©The Author(s) 2019. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2019; 25(26): 3450-3467
Published online Jul 14, 2019. doi: 10.3748/wjg.v25.i26.3450
Genetic testing vs microforceps biopsy in pancreatic cysts: Systematic review and meta-analysis
Sandra Faias, Luisa Pereira, Ângelo Luís, Paula Chaves, Marília Cravo
Sandra Faias, Department of Gastroenterology, Instituto Português de Oncologia de Lisboa de Francisco Gentil, EPE, Lisboa 1099-023, Portugal
Sandra Faias, Paula Chaves, Faculdade de Ciências da Saúde, Universidade da Beira Interior, Covilhã 6200-506, Portugal
Sandra Faias, Luisa Pereira, Ângelo Luís, GRUBI-Grupo de Revisões Sistemáticas, Universidade da Beira Interior, Covilhã 6200-506, Portugal
Luisa Pereira, Centro de Matemática e Aplicações (CMA-UBI), Universidade da Beira Interior, Covilhã 6200-506, Portugal
Ângelo Luís, Centro de Investigação em Ciências da Saúde (CICS-UBI), Universidade da Beira Interior, Covilhã 6200-506, Portugal
Paula Chaves, Department of Pathology, Instituto Português de Oncologia de Lisboa de Francisco Gentil, EPE, Lisboa 1099-023, Portugal
Marília Cravo, Department of Gastroenterology, Hospital Beatriz Ângelo, Loures 2674-514, Portugal
Marília Cravo, Faculdade de Medicina, Universidade de Lisboa, Lisboa 1099-023, Portugal
Author contributions: All authors have contributed to the study concept and design; Faias S, Pereira L and Luís  acquired and interpreted the data and drafted the manuscript, under the supervision of all senior authors; Chaves P and Cravo M critically revised the manuscript; and all authors approved the final version of the manuscript.
Conflict-of-interest statement: The authors have no conflict of interest to disclose.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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:
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: Sandra Faias, MD, Attending Doctor, Research Fellow, Department of Gastroenterology, Instituto Português de Oncologia de Lisboa de Francisco Gentil, EPE, Lisboa 1099-023, Portugal.
Telephone: +351-914310209 Fax: +351-217229855
Received: February 18, 2019
Peer-review started: February 18, 2019
First decision: April 8, 2019
Revised: April 17, 2019
Accepted: May 18, 2019
Article in press: May 18, 2019
Published online: July 14, 2019

Carcinoembryonic antigen (CEA) and cytology in pancreatic cystic fluid are suboptimal for evaluation of pancreatic cystic neoplasms. Genetic testing and microforceps biopsy are promising tools for pre-operative diagnostic improvement but comparative performance of both methods is unknown.


To compare the accuracy of genetic testing and microforceps biopsy in pancreatic cysts referred for surgery.


We performed a literature search in Medline, Scopus, and Web of Science for studies evaluating genetic testing of cystic fluid and microforceps biopsy of pancreatic cysts, with endoscopic ultrasound with fine-needle aspiration (EUS-FNA) prior to surgery and surgical pathology as reference standard for diagnosis. We evaluated the diagnostic accuracy for: 1- benign cysts; 2- mucinous low-risk cysts; 3- high-risk cysts, and the diagnostic yield and rate of correctly identified cysts with microforceps biopsy and molecular analysis. We also assessed publication bias, heterogeneity, and study quality.


Eight studies, including 1206 patients, of which 203 (17%) referred for surgery who met the inclusion criteria were analyzed in the systematic review, and seven studies were included in the meta-analysis. Genetic testing and microforceps biopsies were identical for diagnosis of benign cysts. Molecular analysis was superior for diagnosis of both low and high-risk mucinous cysts, with sensitivities of 0.89 (95%CI: 0.79-0.95) and 0.57 (95%CI: 0.42-0.71), specificities of 0.88 (95%CI: 0.75-0.95) and 0.88 (95%CI: 0.80-0.93) and AUC of 0.9555 and 0.92, respectively. The diagnostic yield was higher in microforceps biopsies than in genetic analysis (0.73 vs 0.54, respectively) but the rates of correctly identified cysts were identical (0.73 with 95%CI: 0.62-0.82 vs 0.71 with 95%CI: 0.49-0.86, respectively).


Genetic testing and microforceps biopsies are useful second tests, with identical results in benign pancreatic cysts. Genetic analysis performs better for low- and high-risk cysts but has lower diagnostic yield.

Keywords: Pancreatic cysts, Endoscopic ultrasound, Endoscopic ultrasound with fine-needle aspiration, Genetic testing, Microforceps biopsy, Molecular analysis, KRAS, Carcinoembryonic antigen, Cytology

Core tip: With the increasing diagnosis of asymptomatic pre-malignant pancreatic cysts, there is a growing need for accurate and affordable diagnostic tests. The goal is to detect and resect early malignancy, while avoiding unnecessary follow-up in benign cysts and surgery in low-risk cysts. Genetic testing is promising, but with current diagnostic limitations, significant costs, logistic difficulties in preserving material for future analysis, and technical complexity, its generalized use seems difficult. If microforceps biopsy proves in larger studies to be safe and to allow correct diagnosis, it may be immediately implemented, because the endoscopic procedure is standard, and histology is widespread in clinics.