Evaluation of confocal laser endomicroscopy for detection of occult gastric carcinoma in CDH1 variant carriers

Abstract

Background: Hereditary diffuse gastric cancer syndrome, attributed to inactivating germline CDH1 variants, is associated with an elevated lifetime risk of gastric cancer. We sought to evaluate cancer detection using probe-based confocal laser endomicroscopy (pCLE) during endoscopic surveillance.

Methods: A prospective, single-institution study was conducted in asymptomatic adults with pathogenic or likely pathogenic (P/LP) CDH1 variants. Subjects received endoscopic gastric surveillance using pCLE in conjunction with the Cambridge method (CM). Abnormalities visualized by pCLE were biopsied, followed by non-targeted mucosal biopsies according to the CM. Primary endpoint was to determine pCLE sensitivity for detection of occult SRC carcinoma compared to CM.

Results: Thirty-six patients with P/LP CDH1 variants underwent endoscopy using pCLE and CM. Majority were female (75%) with median age 47 years. Targeted biopsies of focal abnormalities on WLE were negative for carcinoma. Overall, 19.4% (7/36) patients had SRC detected on ≥1 biopsy. Non-targeted CM biopsies revealed SRC in 11.1% (4/36), whereas pCLE revealed SRC in 16.7% (6/36). Fifteen patients underwent total gastrectomy; all 15 explants contained occult carcinoma. In those 15 patients, the false-negative SRC detection rates for pCLE and CM were 67% and 87%, respectively.

Conclusions: Confocal endomicroscopy alone has low sensitivity for occult cancer detection in CDH1 variant carriers, although it appeared no worse than the current recommended method and required fewer biopsies per patient. A more reliable endoscopic surveillance is needed as a viable alternative to surgery in this high-risk population (ClinicalTrials.gov, Number: NCT03648879).

Keywords: Hereditary gastric cancer; endoscopy; stomach; surveillance.

Conflict of interest statement

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at: http://dx.doi.org/10.21037/jgo-20-430). The authors have no conflicts of interest to declare.

2021 Journal of Gastrointestinal Oncology. All rights reserved.

Figures

Figure 1

Atypical pCLE images of gastric mucosal pathology with matched biopsy photomicrographs. Abnormal appearing confocal laser endomicroscopic image (A) with cross-sectional view of gastric pits displaced by the expansion of the lamina propria by signet ring cells and (B) corresponding biopsy (hematoxylin and eosin, 40×). Abnormal appearing confocal laser endomicroscopic image (C) with cross-sectional view of gastric pits with minimal displacement by stromal edema within lamina propria (D) and corresponding (4 biopsies), anterior fundus.

Figure 2

Probe-based CLE images of gastric mucosa interpreted as normal and confirmed by biopsy with histopathology. Normal appearing confocal laser endomicroscopic image of gastric fundus (A), body (B), antrum (C), and incisura (D).