Indications for Total Gastrectomy in CDH1 Mutation Carriers and Outcomes of Risk-Reducing Minimally Invasive and Open Gastrectomies.

Importance: CDH1 variants are increasingly identified on commercially available multigene panel tests, calling for data to inform counseling of individuals without a family history of gastric cancer.
Objectives: To assess association between CDH1 variant pathogenicity or family history of gastric or lobular breast cancer and identification of signet ring cell cancer and to describe outcomes of risk-reducing minimally invasive and open total gastrectomy. Design, Setting, and Participants: This cohort study was performed from January 1, 2006, to January 1, 2020, in 181 patients with CDH1 germline variants from a single institution. Interventions: Genetic counseling, esophagogastroduodenoscopy, and possible total gastrectomy. Main Outcomes and Measures: CDH1 variant classification, family cancer history, findings of signet ring cell carcinoma at esophagogastroduodenoscopy and surgery, postoperative events and weight changes, and follow-up.
Results: Of 181 individuals with CDH1 germline variants (mean [SD] age at time of testing, 44 [15] years; 126 [70%] female), 165 harbored a pathogenic or likely pathogenic variant. Of these patients, 101 underwent open (n = 58) or minimally invasive (n = 43) total gastrectomy. Anastomotic leaks that required drainage were infrequent (n = 3), and median long-term weight loss was 20% (interquartile range [IQR], 10%-23%). In those undergoing minimally invasive operations, more lymph nodes were retrieved (median, 28 [IQR, 20-34] vs 15 [IQR, 9-19]; P < .001) and the hospital stay was 1 day shorter (median, 6 [IQR, 5-7] vs 7 [IQR, 6-7] days; P = .04). Signet ring cell cancer was identified in the surgical specimens of 85 of 95 patients (89%) with a family history of gastric cancer and 4 of 6 patients (67%) who lacked a family history. Among the latter 6 patients, 4 had a personal or family history of lobular breast cancer, including 2 with signet ring cell cancer. Of the 16 patients with pathogenic or likely pathogenic CDH1 variants who presented with locally advanced or metastatic gastric cancer, 3 (19%) had no family history of gastric cancer or personal or family history of lobular breast cancer. Conclusions and Relevance: Total gastrectomy may be warranted for patients with pathogenic or likely pathogenic CDH1 variants and a family history of gastric or lobular breast cancer and may be appropriate for those without a family history. A minimally invasive approach is feasible and may be preferred for selected patients.