Surgical management of hereditary diffuse gastric cancer
- Debrah Wirtzfeld, MD, MSc, FRCSC, FACS
Debrah Wirtzfeld, MD, MSc, FRCSC, FACS
- Associate Professor of Surgery, Oncology, Community Health Sciences and Biochemistry & Medical Genetics
- University of Manitoba
- Pamela Hebbard, MD, FRCS
Pamela Hebbard, MD, FRCS
- Assistant Professor of Surgery
- University of Manitoba
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 .
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'.)
INDICATIONS FOR PROPHYLACTIC TOTAL GASTRECTOMY
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. .
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- INDICATIONS FOR PROPHYLACTIC TOTAL GASTRECTOMY
- CDH1 mutation carriers from HDGC families
- CDH1 mutation carriers not from HDGC families
- TIMING OF PROPHYLACTIC TOTAL GASTRECTOMY
- - Young patients
- - Old patients
- Eating disorders
- Women of child-bearing age
- PREOPERATIVE EVALUATION
- Genetic and family counseling
- Nutritional evaluation and counseling
- Preoperative imaging and endoscopy
- - Abdominal imaging
- - Endoscopy
- GASTRECTOMY AND RECONSTRUCTION
- Margins of resection
- Laparoscopic versus open gastrectomy
- Extent of lymph node dissection
- PERIOPERATIVE MORBIDITY AND MORTALITY
- PATIENTS WHO REFUSE SURGERY
- SUMMARY AND RECOMMENDATIONS