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Surgical management of hereditary diffuse gastric cancer

Debrah Wirtzfeld, MD, MSc, FRCSC, FACS
Pamela Hebbard, MD, FRCS
Section Editor
David I Soybel, MD
Deputy Editor
Wenliang Chen, MD, PhD


Diffuse gastric carcinoma (DGC) is a highly invasive tumor that is characterized by a late presentation and poor prognosis. Diffuse gastric cancer represents about 5 percent of all invasive gastric cancers. An inherited form of DGC, hereditary diffuse gastric cancer (HDGC) can be caused by mutations in the E-cadherin (CDH1) gene [1-3] or the alpha-E-catenin (CTNNA1) gene [4].

Since the lifetime risk of developing gastric cancer for CDH1 mutation carriers from HDGC families is very high (70 percent for men and 56 percent for women), prophylactic total gastrectomy is often recommended for them at an early age [5-10].

The surgical management of HDGC will be reviewed here. The genetics and pathogenesis of HDGC, as well as issues related to screening for HDGC and surveillance for breast and other cancers in CDH1 mutation carriers are discussed separately. (See "Hereditary diffuse gastric cancer" and "Pathology and molecular pathogenesis of gastric cancer", section on 'Diffuse type cancers'.)


For patients from a hereditary diffuse gastric cancer (HDGC) family who have tested positive for a pathogenic germline CDH1 mutation, we recommend a prophylactic total gastrectomy to reduce the risk of developing invasive gastric cancer. For patients with a CDH1 mutation but who are not from an HDGC family, we recommend individualized evaluation at an experienced center before prophylactic total gastrectomy is offered.

CDH1 mutation carriers from HDGC families — Asymptomatic patients with a family history of HDGC and CDH1 mutations have a high probability of developing signet ring cell adenocarcinoma of the stomach that cannot be diagnosed on endoscopy. When symptoms arise, the diagnosis can be made by endoscopy, but such patients may already have metastases and decreased survival. Thus, surveillance endoscopy is of limited value, and prophylactic total gastrectomy is recommended for patients with family history of HDGC and CDH1 mutations. [11].


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Literature review current through: Sep 2016. | This topic last updated: May 23, 2016.
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