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 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.
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.