Observational Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastrointest Endosc. Nov 16, 2021; 13(11): 555-564
Published online Nov 16, 2021. doi: 10.4253/wjge.v13.i11.555
Needle-based confocal endomicroscopy in the discrimination of mucinous from non-mucinous pancreatic cystic lesions
Helga Bertani, Raffaele Pezzilli, Flavia Pigò, Mauro Bruno, Claudio De Angelis, Guido Manfredi, Gabriele Delconte, Rita Conigliaro, Elisabetta Buscarini
Helga Bertani, Flavia Pigò, Rita Conigliaro, Gastroenterology and Digestive Endoscopy Unit, Azienda Ospedaliero Universitaria Policlinico di Modena, Modena 41124, Italy
Raffaele Pezzilli, Department of Internal Medicine, Policlinico S.Orsola Malpighi, Bologna 40121, Italy
Mauro Bruno, Claudio De Angelis, Gastroenterology and Digestive Endoscopy Unit, AOU Città della Salute e della Scienza, University of Turin, Turin 10100, Italy
Guido Manfredi, Elisabetta Buscarini, Gastroenterology and Digestive Endoscopy Department, Ospedale Maggiore, Crema 26013, Italy
Gabriele Delconte, Department of Diagnostic Endoscopy and Endoscopic Surgery, Istituto Nazionale Tumori, Milano 20019, Italy
Author contributions: Bertani H and Buscarini E conceived the study; Pezzilli R and Pigò F conducted the statistical analyses; Bertani H and Pigò F drafted the manuscript; Bruno M, De Angelis C, Manfredi G and Delconte G collected the data; Conigliaro R and Buscarini E reviewed the manuscript.
Institutional review board statement: The study was carried out in accordance with the Declaration of Helsinki and was approved by Ethical Committee of Baggiovara Hospital in Modena (Prot. 16/11/2015 prat n 4327).
Informed consent statement: All patients received written information about the study with results and possible complications. They all provide informed consent, as a negation of a written informed consent resulted in exclusion of the patient from the study.
Conflict-of-interest statement: The authors declare no conflicts of interest.
Data sharing statement: The dataset is available. For more information please contact Pigo.flavia@aou.mo.it. We can provide the anonymized version.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
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: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Helga Bertani, MD, Academic Research, Gastroenterology and Digestive Endoscopy Unit, Azienda Ospedaliero Universitaria Policlinico di Modena, Via del Pozzo 71, Modena 41124, Italy. bertani.helga@aou.mo.it
Received: February 23, 2021
Peer-review started: February 23, 2021
First decision: June 17, 2021
Revised: June 25, 2021
Accepted: September 6, 2021
Article in press: September 6, 2021
Published online: November 16, 2021
ARTICLE HIGHLIGHTS
Research background

Some pancreatic cystic lesions (PCLs) have unequivocal malignant potential, but the precise determination of the risk of progression with endoscopic ultrasound (EUS), fine-needle aspiration (FNA), analysis of carcinoembryonic antigen (CEA) level, and cytology is still challenging. Among the novel tools for assessing PCLs, needle-based confocal endomicroscopy (nCLE) has been identified as one of the most sensitive, but some concerns have been raised about its safety and reproducibility.

Research motivation

The first clinical trials published described a correlation between nCLE and histological features, and established the criteria for characterizing the most frequent type of cysts. However, no multicenter prospective studies have been performed at the time of study conception to evaluate the safety of the procedure and interobserver agreement (IOA).

Research objectives

The purpose of this multicenter prospective study was to evaluate the diagnostic accuracy of EUS-guided nCLE to differentiate mucinous from non-mucinous in PCLs compared to standard of care, by analysis of intracystic CEA and amylase level and/or cytology vs surgical pathology.

Research methods

The strength of the study is its observational design in high-volume centers compared to the single-center studies previously published. All nCLE videos were independently reviewed by 6 observers blind to clinical or imaging information; each investigator provided a final diagnosis, and if the disagreement between reviewers was > 20%, videos were discussed together in order to reach a final nCLE consensus diagnosis. In the event of persistent disagreement among investigators, the videos were considered false negatives.

Research results

A total of 59 patients were enrolled in this study to receive EUS-FNA and nCLE. The procedure was technically feasible in 95% of patients; nCLE sensitivity, specificity, and accuracy for the diagnosis of mucinous lesions were 80% [95% confidence interval (CI): 65-90], 100% (95%CI: 72-100), and 84% (95%CI: 72-92), respectively, and for distinguishing mucinous from non-mucinous lesions compared to intracystic CEA > 192 ng/mL were 58% (95%CI: 43-72), 100% (95%CI: 73-100), and 67% (95%CI: 53-78), respectively. IOA for nCLE diagnosis was 0.76, and 10% of adverse events were recorded.

Research conclusions

Our study confirmed the feasibility of nCLE and its excellent performance in the discrimination of mucinous vs non-mucinous lesions. This new finding confirms the possibility of an accurate pre-operative diagnosis. The strength of the study was the multicenter, prospective observational design and the selection of a study group of real undetermined pancreatic cysts without pancreatic duct communication and free of worrisome features; this was also a weakness due to the low number of cases with surgical/histological diagnosis. The excellent performance of nCLE opens various possible scenarios for the management of undetermined PCLs.

Research perspectives

Future research should include fine-needle biopsies with biopsy forceps to improve pathological diagnosis without surgery.