Published online Jul 14, 2019. doi: 10.3748/wjg.v25.i26.3450
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 of pancreatic cystic fluid (PCF) obtained pre-operatively with endoscopic ultrasound with fine-needle aspiration (EUS-FNA) are suboptimal for diagnostic evaluation of pancreatic cystic neoplasms. Genetic testing of PCF and microforceps biopsy obtained by EUS-FNA are promising tools for pre-operative diagnostic improvement. The comparative performance of both methods has not been previously studied.
In the last decade numerous studies have shown that genetic analysis of aspirates obtained by EUS-FNA provided a better characterization of pancreatic cysts than standard CEA and cytology. Next-generation sequencing (NGS) is a very sensitive technique for detection of genetic mutations in pre-defined panels of cancer genes, even in samples with limited DNA content, such as PCF. NGS requires storage, infrastructure, data processing, expert personnel, and large numbers of samples need to be cost-effective. These reasons make the implementation of NGS in clinical practice still a matter of debate. The clinical need of better diagnostic tests in pancreatic cysts led to the development of a through-the-needle miniature biopsy device for use during EUS-FNA. The Moray micro forceps biopsy device (US Endoscopy, Mentor, Ohio) is disposable and can pass through a standard 19-gauge EUS-FNA needle that is already used routinely. It allows tissue sampling from the cyst wall, septa or mural nodules and the obtention of a histological evaluation of the epithelial architecture and subepithelial stroma, with improved pancreatic cyst diagnosis.
To compare the diagnostic accuracy of genetic testing and microforceps in the diagnosis of pancreatic cystic neoplasms 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 EUS-FNA prior to surgery. We used surgical pathology as reference standard for diagnosis. We evaluated the diagnostic accuracy for: benign cysts; mucinous low-risk cysts; high-risk cysts; the diagnostic yield; and rate of correctly identified cysts with microforceps biopsy and molecular analysis.
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. The diagnostic yield was higher in microforceps biopsies than in genetic analysis, but the rates of correctly identified cyst types were identical.
This study underlines the diagnostic value of both MA and MFB, with higher diagnostic accuracy of MA than MFB for both low-risk and high-risk mucinous cysts. Genetic analysis should not be replaced by MFB in this context. However, MA has higher accuracy in the diagnosis of malignant and high-risk cysts.
For the present time, MA and MFB can only be recommended as complementary or as second line tests in case CEA and cytology of PCF are non-diagnostic. In the future, for MA to become relevant in routine clinical care, its role must be confirmed, in order to become a first line test with clinical impact in cyst diagnosis, prognosis, and patient management. MA, both in PCF and peripheral blood, for multiple simultaneous biomarkers and non-invasive diagnosis and risk stratification would be valuable. If MFB proves in larger studies to be safe and to allow a correct diagnosis of pancreatic cysts, it may be immediately implemented in clinics. MFB may be especially useful for benign lesions, for which both surgery and surveillance are unnecessary, with uncertain diagnosis due to current diagnostic limitations. For both tests, larger validation studies are missing.