Evaluation of Confocal Laser Endomicroscopy for Detection of Occult Gastric Carcinoma in CDH1 Variant Carriers

AbstractBackground & AimsHereditary diffuse gastric cancer, attributed to inactivating germline CDH1 variants, is characterized by signet ring cell (SRC) morphology. We sought to evaluate the occult cancer detection rate using probe-based confocal laser endomicroscopy (pCLE) during endoscopic surveillance.MethodsA 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 consensus Cambridge method (CM) of non-targeted mucosal biopsies. Systematic examination was performed with white light endoscopy (WLE) and pCLE. Abnormalities visualized by pCLE were biopsied, followed by non-targeted mucosal biopsies according to the CM. Pathologists were blinded to clinical and endomicroscopic findings. Primary endpoint was to determine pCLE sensitivity for detection of occult SRC carcinoma compared to CM.ResultsThirty-six patients with P/LP CDH1 variants underwent endoscopy using pCLE and CM. Majority were female (75%) with median age 47 years. Median procedure time was 52.5 minutes, without serious adverse events. 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, 5 of whom had SRC at endoscopy, 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.ConclusionsConfocal endomicroscopy alone has low sensitivity for occult cancer detection in CDH1 variant carriers. Reliable endoscopic surveillance is lacking as an alternative to prophylactic surgery in this high-risk population. (http://ClinicalTrials.gov, Number: NCT03648879).