Advanced endoscopic imaging for detecting and guiding therapy of early neoplasias of the esophagus

Abstract

Esophageal cancers, largely adenocarcinoma in Western countries and squamous cell cancer in Asia, present a significant burden of disease and remain one of the most lethal of cancers. Key to improving survival is the development and adoption of new imaging modalities to identify early neoplastic lesions, which may be small, multifocal, subsurface, and difficult to detect by standard endoscopy. Such advanced imaging is particularly relevant with the emergence of ablative techniques that often require multiple endoscopic sessions and may be complicated by bleeding, pain, strictures, and recurrences. Assessing the specific location, depth of involvement, and features correlated with neoplastic progression or incomplete treatment may optimize treatments. While not comprehensive of all endoscopic imaging modalities, we review here some of the recent advances in endoscopic luminal imaging, particularly with surface contrast enhancement using virtual chromoendoscopy, highly magnified subsurface imaging with confocal endomicroscopy, optical coherence tomography, elastic scattering spectroscopy, angle-resolved lowcoherence interferometry, and light scattering spectroscopy. While there is no single ideal imaging modality, various multimodal instruments are also being investigated. The future of combining computer-aided assessments, molecular markers, and improved imaging technologies to help localize and ablate early neoplastic lesions shed hope for improved disease outcome.

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“…The incidence of EAC is increasing in Western countries, likely due to widespread risk factors as gastro-esophageal reflux, central obesity, and increasing age [62]. Although the incidence of ESCC has declined in China in recent years, the absolute incidence is high because of the large population [35].…”

“…Probe-based CLE (pCLE) provides both surface and subsurface images of esophageal mucosa, capturing near-microscopic images at approximately 150 µm of depth via a flexible mini-probe introduced through the accessory channel of standard endoscopes [62]. However, the endoscope-integrated system for CLE (eCLE), which provided images at different depths from 0 to 250 mlm and allowed a free accessory channel for esophageal biopsy, is no longer available on the market [62]. CLE investigations require contrast agents, including intravenous fluorescein sodium or topical acriflavine hydrochloride and cresyl violet.…”

“…CLE investigations require contrast agents, including intravenous fluorescein sodium or topical acriflavine hydrochloride and cresyl violet. When fluorescein is administered intravenously, it stains the extracellular matrix of the surface epithelium, whereas topical acriflavine and cresyl violet stain the nuclei of superficial layers of the mucosa [62]. In 2011, the Miami consensus classification of CLE provided guidelines to distinguish normal squamous epithelium, BE with and without dysplasia and intramucosal carcinoma [63].…”

“…A balloon-based system generates a circumferential scan of 6 cm segments of the esophagus to a depth of 3 mm into the mucosal and submucosal layers with 7 µm axial resolution [65]. Unlike CLE, VLE does not require intravenous contrast agents [62]. In 2017, VLE diagnostic criteria for the diagnosis of squamous esophagus, NDBE and BE was proposed [66].…”

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“…Reverse transcriptase quantitative polymerase chain reaction (RTqPCR) analyses of selected target genes were carried out using SYBR Green I-based real-time PCR, as described 33 , and specific primers against CCL5 , CXCL1 , CXCL3 , CYLD , IL1B , IL23A , MMP3, PPBP and GAPDH (Supplementary Table S2 ). The data was calculated as the ratio of each gene to GAPDH.…”