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Upper Gastrointestinal (lips to ileocecal valve, including esophagus and stomach)

E441: Lymph node status in patients with CDH1 mutation who undergo prophylactic total gastrectomy.

Introduction: Hereditary diffuse gastric cancer (HDGC) is frequently associated with pathogenic mutations of the E-cadherin (CDH1) gene, which confers significantly increased risk of developing diffuse type/signet ring cell gastric cancer. Prophylactic total gastrectomy (PTG) is often recommended in patients with a pathogenic CDH1 mutation; however, limited data exists regarding the extent of lymphadenectomy that should be performed at the time of PTG. The objective of this study is to evaluate the lymph node status of patients with CDH1 mutation who undergo PTG.

Methods: A retrospective chart review was conducted for a consecutive series of patients at a single institution who were taken to the operating room for PTG from 2006-2021. Clinicopathologic variables were reviewed to determine the frequency of nodal involvement and survival outcomes.  

Results: Seventy-nine patients were included in this study. The median age at time of surgery was 37 years (range 16-72); 73% were female. Seventy-four patients (94%) identified as White, non-Hispanic. PTG was performed via a laparoscopic-assisted approach in 70 patients (89%). Regional lymphadenectomy was performed in 76 patients (96%); formal D1 lymphadenectomy was performed in 1 patient, and formal modified D2 lymphadenectomy was performed in 2 patients. Foci of signet ring cells were identified in 74 resection specimens (94%). A median of 16 (range 0-700) foci of cancer were identified. The greatest depth of invasion was Tis in two patients, T1a in 70 patients (89%), T3 in one patient and T4 in one patient. A median of 10 lymph nodes (range 0-32) were evaluated. No pathologically positive lymph nodes were identified in any resection specimen. Median follow-up has been 37 months (range 3-181); 78 patients (99%) are alive as of the time of authorship of this abstract as one patient died of non-cancer related causes.

Conclusions: In a large study of consecutive patients with pathogenic CDH1 mutation undergoing PTG, no pathologically positive lymph nodes were identified among resection specimens. In addition, no patients died of gastric cancer or developed metastatic disease. If similar findings are reproduced in a larger patient cohort and with longer follow-up, this data would support omission of extended lymphadenectomy in this patient population.

Learning Objectives:

  • think critically about the need for extended lymphadenectomy in prophylactic gastrectomy for CDH1 mutation
  • Know why prophylactic total gastrectomy is indicated in patients with CDH1 mutation
  • Know why patients with CDH1 mutation are at higher risk of developing gastric cancer