Confocal Laser Endomicroscopy in Gastrointestinal and Pancreatobiliary Diseases: A Systematic Review and Meta-Analysis

Abstract

Confocal laser endomicroscopy (CLE) is an endoscopic-assisted technique developed to obtain histopathological diagnoses of gastrointestinal and pancreatobiliary diseases in real time. The objective of this systematic review is to analyze the current literature on CLE and to evaluate the applicability and diagnostic yield of CLE in patients with gastrointestinal and pancreatobiliary diseases. A literature search was performed on MEDLINE, EMBASE, Scopus, and Cochrane Oral Health Group Specialized Register, using pertinent keywords without time limitations. Both prospective and retrospective clinical studies that evaluated the sensitivity, specificity, or accuracy of CLE were eligible for inclusion. Of 662 articles identified, 102 studies were included in the systematic review. The studies were conducted between 2004 and 2015 in 16 different countries. CLE demonstrated high sensitivity and specificity in the detection of dysplasia in Barrett's esophagus, gastric neoplasms and polyps, colorectal cancers in inflammatory bowel disease, malignant pancreatobiliary strictures, and pancreatic cysts. Although CLE has several promising applications, its use has been limited by its low availability, high cost, and need of specific operator training. Further clinical trials with a particular focus on cost-effectiveness and medicoeconomic analyses, as well as standardized institutional training, are advocated to implement CLE in routine clinical practice.

Advanced endoscopic imaging in gastric neoplasia and preneoplasia

“…A recent meta-analysis43 performed on CLE and gastric diseases, focused on three domains: (1) detection and diagnosis of polyps and neoplastic lesions (three studies, sensitivity 85% (95% CI 78% to 91%, I 2 =52.3%), specificity 99% (95% CI 98% to 99%, I 2 =92.92%), AUC=0.929), (2) gastritis and gastric metaplasia (six studies, sensitivity 94% (95% CI 92% to 96%, I 2 =54.8%), specificity 95% (CI 92% to 97%, I 2 =55.6%), AUC=0.983) and (3) H. pylori -related gastritis (two studies, sensitivity 86% (95% CI 76% to 93%, I 2 =0), specificity 93% (95% CI 87% to 97%, I 2 =2.6%)). The pooled analyses demonstrated CLE yields remarkable sensitivity and specificity, in per patient analysis in all three domains.…”

Novel diagnostic and therapeutic modalities using endoscopic ultrasound in pancreatic disease

“…13,30 Fluorescent light is then reflected from the selected tissue through the aperture, which excludes any light reflected at angles that do not refocus into the lens. [31][32][33][34] In essence, this adjunct to EUS acts as an "optical biopsy" by providing realtime tissue histopathology. 32,35 Intravenous fluorescent agents are used to image the tissue mucosa.…”

“…[33][34][35] Currently, two primary modalities of CLE are available: endoscope-based confocal laser endomicroscopy (eCLE) created by Pentax (Pentax America, Montvale, NJ, USA) and Optiscan (Optiscan, Notting Hill, Australia) which incorporates the confocal scanner into the distal tip of conventional endoscopes and a probe-based confocal laser endomicroscopy (pCLE) which is miniaturized to 250-300 μm, allowing it to be introduced through endoscopic accessory channels (Cellvizio; Mauna Kea Technologies, Paris, France). 13,33,34,35 This is an exciting advancement in EUS, as it can guide treatment decisions for various diseases in real-time while also preventing unnecessary biopsies. eCLE has been used to optimize endoscopic detection of colonic polyps, dysplasia in Barrett esophagus, and neoplasia in inflammatory bowel disease.…”

“…This is largely due to pCLE's size, which allows it to be passed through the EUS-FNA needle system with the CholangioFlex confocal probe (Mauna Kea Technologies) and access the bile and pancreatic ducts. 13,[32][33][34][35]38 Distinguishing malignant from benign biliary strictures remains a common diagnostic challenge despite the advent of improved computed tomography (CT), magnetic resonance, and endoscopic imaging. Despite use of brush cytology to aid in endoscopic diagnosis, sensitivity remains less than ideal, often not exceeding 70%.…”

“…Fugazza et al 34 recently performed a meta-analysis of 8 available studies on the evaluation of biliary strictures with pCLE to find a pooled sensitivity of 90% (95% confidence interval [CI] = 0.86-0.94) and specificity of 72% (95% CI = 0.65-0.79). This data suggests that pCLE may have aid in improving earlier detection of pancreatobiliary malignancies and influencing appropriate management.…”