Utilizing fourth-generation endocytoscopy and the 'enlarged nuclear sign' for in vivo diagnosis of early gastric cancer

Abstract

Background and study aims Fourth-generation endocytoscopy is an ultra-high magnification endoscopic technique designed to provide excellent quality in vivo histologic assessment of gastrointestinal lesions. This study aims to evaluate the diagnostic accuracy of endocytoscopy in early gastric cancer diagnosis. Patients and methods A single-center, retrospective analysis of prospectively collected data from all gastric endocytoscopic examinations was conducted. Two expert endoscopists, blinded to white-light and narrow-band imaging findings as well as histopathologic diagnosis, independently reviewed and diagnosed all endocytoscopic images. A newly recognized "enlarged nuclear sign" was detected, and its implication in early gastric cancer diagnosis was evaluated. The diagnostic performance of fourth-generation endocytoscopy was assessed while using the gold standard histopathology as a reference. Results Forty-three patients (mean age±SD, 72.6 ± 12.1 years; 31 males) were enrolled. Based on histopathology, 23 had well-differentiated adenocarcinomas, four adenomas, and 16 non-neoplastic lesions. The sensitivity, specificity, and accuracy of fourth-generation endocytoscopy for gastric cancer diagnosis were 87.0 % (95 % CI: 67.9 - 95.5), 80.0 % (95 % CI: 58.4 - 91.9), and 83.7 % (95 % CI: 70.0 - 91.9) by endoscopist A; and 91.3 % (95 % CI: 73.2 - 97.6), 75.0 % (95 % CI: 53.1 - 88.8), and 83.7 % (95 % CI: 70.0 - 91.9) by endoscopist B. The inter-observer agreement, Kappa statistic = 0.71 (95 % CI: 0.50 - 0.93), was good. The sensitivity, specificity, and accuracy of the enlarged nuclear sign for early gastric cancer diagnosis were 87.0 % (95 % CI: 67.9 - 95.5), 95.0 % (95 % CI: 76.4 - 99.1), and 90.7 % (95 % CI: 78.4 - 96.3) by endoscopist A; and 82.6 % (95 % CI: 62.9 - 93.0), 85.0 % (95 % CI: 64.0 - 94.8), and 83.7 % (95 % CI: 70.0 - 91.9) by endoscopist B. The inter-observer agreement, Kappa statistic = 0.68 (95 % CI: 0.51 - 0.89) was good. Conclusion: Fourth-generation endocytoscopy appears to aid in the diagnosis of early gastric cancer, particularly well-differentiated adenocarcinomas, due to its good diagnostic accuracy and identification of the "enlarged nuclear sign," and deserves further evaluation in future studies.

Fig. 1

CM double staining. a An 11-cc staining solution is prepared consisting of 10 cc of crystal violet and 1 cc of methylene blue. b In a separate 10-cc syringe, 1 cc of the solution is aspirated with 9 cc of air and is used for spraying.

Fig. 2

EC classification of gastric mucosa. Representative pictures differentiating EC1 (normal), EC2 (adenoma), and EC3 (carcinomas).

Fig. 3

Normal gastric mucosa. a Endocytoscopic findings of normal gastric mucosa showing regular glands, smooth surfaces and soft edges, well-preserved lumen, and small uniformly sized rounded nuclei with poor staining. b Histologic appearance of normal gastric mucosa

Fig. 4

Well-differentiated adenocarcinoma. a Endocytoscopic findings of well-differentiated adenocarcinoma showing irregular and distorted glands and the strongly stained “enlarged nuclear sign” (yellow arrows). b Histologic appearance of well-differentiated adenocarcinoma.

Fig. 5

“Enlarged nuclear sign”. Representative pictures of the “enlarged nuclear sign” (yellow arrows) by endocytoscopy a and by histopathology b depicting the striking characteristic of nuclear “taking over” the cell surface.

Fig. 6

Early gastric cancer case diagnosed using fourth-generation endocytoscopy. a, b A lesion in the antrum observed by white-light endoscopy. c Endocytoscopic findings revealed non-neoplastic glands of the surrounding mucosa, d while the highly dysplastic area showed distortion of glands and presence of the “enlarged nuclear sign” (yellow arrows).