The role of endoscopy in the management of hereditary diffuse gastric cancer syndrome

Abstract

Hereditary diffuse gastric cancer (HDGC) syndrome is an inherited cancer risk syndrome associated with pathogenic germline CDH1 variants. Given the high risk for developing diffuse gastric cancer, CDH1 carriers are recommended to undergo prophylactic total gastrectomy for cancer risk reduction. Current guidelines recommend upper endoscopy in CDH1 carriers prior to surgery and then annually for individuals deferring prophylactic total gastrectomy. Management of individuals from HDGC families without CDH1 pathogenic variants remains less clear, and management of families with CDH1 pathogenic variants in the absence of a family history of gastric cancer is particularly problematic at present. Despite adherence to surveillance protocols, endoscopic detection of cancer foci in HDGC is suboptimal and imperfect for facilitating decision-making. Alternative endoscopic modalities, such as chromoendoscopy, endoscopic ultrasound, and other non-white light methods have been utilized, but are of limited utility to further improve cancer detection and risk stratification in HDGC. Herein, we review what is known and what remains unclear about endoscopic surveillance for HDGC, among individuals with and without germline CDH1 pathogenic variants. Ultimately, the use of endoscopy in the management of HDGC remains a challenging arena, but one in which further research to improve surveillance is crucial.