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

Samuel A Schueler; Lauren A Gamble; Bryan F Curtin; Samantha M Ruff; Maureen Connolly; Cathleen Hannah; Martha Quezado; Markku Miettinen; Maureen George; Andrew M Blakely; Jonathan M Hernandez; Theo Heller; Christopher Koh; Jeremy L Davis

doi:10.21037/jgo-20-430

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

J Gastrointest Oncol. 2021 Apr;12(2):216-225. doi: 10.21037/jgo-20-430.

Affiliations

¹ Digestive Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA.
² Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
³ Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA.
⁴ Clinical Center Nursing Department, National Institutes of Health, Bethesda, MD, USA.

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.

Associated data

ClinicalTrials.gov/NCT03648879