Diagnostic accuracy of EUS-guided through-the-needle-biopsies and simultaneously obtained fine needle aspiration for cytology from pancreatic cysts: A systematic review and meta-analysis

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Abstract

Objectives

To address the diagnostic accuracy of endoscopic ultrasound guided through-the-needle-biopsies (TTNBs) and simultaneously obtained cytology samples from pancreatic cysts compared to the final histopathological diagnosis of the surgical specimen, and to give an overview of ancillary tests performed on TTNBs.

Methods

A literature search was conducted in MEDLINE, Embase and Scopus. Studies were included in the meta-analysis, if they had data for TTNB, cytology and a surgical specimen of pancreatic cysts as reference standard. The assessment of the risk of bias and quality of the included studies was conducted using the modified QUADAS-2 tool.

Results

Ten studies with 99 patients were included in the meta-analysis. Data regarding study design and clinicopathological features were extracted systematically. For TTNB, pooled sensitivity was 0.86 (95 % CI 0.62−0.96), specificity 0.95 (95 % CI 0.79−0.99) and area under the curve (AUC) 0.86 for the diagnosis of a mucinous cyst and pooled sensitivity was 0.78 (95 % CI 0.61−0.89), specificity 0.99 (95 % CI 0.90−0.99) and AUC 0.92 for the diagnosis of a high-risk cyst. For a specific diagnosis, pooled sensitivity was 0.69 (95 % CI 0.50−0.83), specificity 0.47 (95 % CI 0.28−0.68) and AUC 0.49. For cytology performed simultaneously, pooled sensitivity was 0.46 (95 % CI 0.35−0.57), specificity 0.90 (95 % CI 0.46−0.99) and AUC 0.64 for the diagnosis of mucinous cysts, and pooled sensitivity was 0.38 (95 % CI 0.23−0.55), specificity 0.99 (95 % CI 0.90−0.99) and AUC 0.84 for the diagnosis of a high-risk cyst. For a specific diagnosis, pooled sensitivity was 0.29 (95 % CI 0.21−0.39), specificity 0.45 (95 % CI 0.25−0.66) and AUC 0.30. Furthermore, immunohistochemical stains can be useful to establish the specific cyst subtype.

Conclusions

TTNBs have a higher sensitivity and specificity than cytology for the diagnosis of mucinous cyst and high- risk cysts of the pancreas.

Introduction

The incidence of pancreatic cystic lesions (PCLs) is rising due to extensive use of imaging techniques as part of routine clinical practice [1]. Some PCLs have the potential for malignant transformation and are considered precursor lesions for pancreatic ductal adenocarcinoma (PDAC) such as intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) whereas serous cystic neoplasms (SCNs) are considered benign entities [2]. This presents a dilemma for the multidisciplinary team in deciding which cysts to resect and which to enroll in a clinical follow up program. Currently, the Fukuoka guidelines [3] and the recent European guideline [4] provides the diagnostic algorithm for the clinical management of PCLs, and Endoscopic Ultrasound (EUS) with fine needle aspiration (FNA) is the foundation of the algorithm, stratifying the PCLs according to the presence of worrisome features such as mural nodules, wall thickening or pancreatic duct dilatation. The aspirated cyst fluid is analyzed for Carcinoembryonic Antigen (CEA) and cytology, both of which have a low sensitivity for detecting mucinous cysts [5]. Endoscopic ultrasound guided through-the-needle-biopsy (TTNB) is a novel diagnostic method for endoscopic evaluation of pancreatic cysts. TTNBs are obtained using a microbiopsy forceps used in conjunction with an ultrasonic endoscope where it is passed through a 19-gauge EUS-FNA needle. TTNBs have shown promising results regarding diagnostic yield [6] and the adequacy of the tissue for histology as well as for molecular analysis [7].

Several retrospective and prospective series have been published regarding the utility and diagnostic yield of TTNBs with promising results [6,[8], [9], [10], [11], [12]]. The primary aim of this review and meta-analysis is to evaluate the sensitivity and specificity of the TTNB and FNA for cytology when compared to the resected specimen. Furthermore, to summarize the specimen processing and additional diagnostic tests being performed on TTNBs in order to facilitate uniform diagnostics of TTNBs across centers for management of PCLs.

Section snippets

Materials and methods

The systematic review presented here is conducted in accordance with the PRISMA-DTA statement [13]. The protocol for this systematic review was registered on PROSPERO (ID: CRD42020164214).

Systematic review

The literature search generated 674 results (Fig. 1). The titles and abstracts were screened and initially, 594 papers were excluded due to irrelevance of topic. Additionally, one paper was included by screening references [17]. Thirty papers were reviewed by full-text, and 15 papers were excluded based on the exclusion criteria described above. Fifteen papers were included in the qualitative synthesis [[7], [8], [9], [10], [11], [12],[17], [18], [19], [20], [21], [22], [23], [24], [25]] and

Discussion

A systematic review of the literature was done, and a meta-analysis was performed for a subset of the included studies, all with available data regarding TTNB and concomitant cytology from pancreatic cysts with a resected specimen as the reference standard. The result of the meta-analysis showed a high sensitivity and specificity of the TTNB for the diagnosis of mucinous cysts as well as high-risk cysts of any kind. The sensitivity and specificity for the cytology-sample performed

Data availability statement

The authors confirm that the data supporting the findings of this study are available within the articles supplementary materials.

CRediT authorship contribution statement

Charlotte Vestrup Rift: Conceptualization, Methodology, Formal analysis, Investigation, Data curation, Writing - original draft, Writing - review & editing, Project administration, Funding acquisition. David Scheie: Conceptualization, Methodology, Writing - review & editing. Anders Toxværd: Conceptualization, Methodology, Writing - review & editing. Bojan Kovacevic: Conceptualization, Methodology, Writing - review & editing. Pia Klausen: Conceptualization, Methodology, Writing - review &

Declaration of Competing Interest

Charlotte Vestrup Rift received research grants from Rigshospitalets Research Foundation, The Novo Nordisk Foundation, Danish Cancer Society, and Danish Cancer Research Foundation. The funding sources had no role in conducting the study or preparing the manuscript. Peter Vilmann received a speaker’s honorarium from US endoscopy, who sells the micro forceps, but the company had no role in conducting the study or preparing the manuscript. The remaining authors declare no conflicts of interests.

Acknowledgements

This work was supported by Rigshospitalets Research Foundation, The Novo Nordisk Foundation, Danish Cancer Society, and Danish Cancer Research Foundation.

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