Elsevier

Surgery

Volume 130, Issue 4, October 2001, Pages 612-619
Surgery

Central Surgical Association
Prophylactic total gastrectomy for familial gastric cancer*

Presented at the 58th Annual Meeting of the Central Surgical Association, Tucson, Ariz, March 7-10, 2001.
https://doi.org/10.1067/msy.2001.117099Get rights and content

Abstract

Background. An autosomal dominant syndrome of diffuse gastric cancer has been reported with germline mutations in the E-cadherin (CDH1) gene and has been identified in approximately 14 families and 50 individuals worldwide. Penetrance of the gene is 70% to 80%, and the average age of onset of gastric cancer is 37 years. These characteristics have led to the consideration of prophylactic total gastrectomy in family members with CDH1 mutations. Methods. We report here the first use of prophylactic gastrectomy in 6 asymptomatic members of 2 families (2 males, 4 females; ages 22, 27, 28, 35, 39, and 40) based on family pedigree and genetic analysis. Total gastrectomy was performed via an upper midline incision, and reconstruction of the gastrointestinal tract was done via a Roux-en-Y esophagojejunostomy. Complete removal of all gastric mucosa was documented intraoperatively, and confirmation was made that only esophageal mucosa remained at the proximal specimen margin. Results. The gastric specimens appeared normal, and the results of routine pathologic examination were negative for cancer. All specimens from patients who tested positive for E-cadherin mutations were subjected to a research protocol of microscopic sectioning in which 150 to 250 tissue blocks were examined. All of these patients had microscopic foci of cancer, often at multiple sites, with overlying normal gastric mucosa. Conclusions. E-cadherin gene mutations in association with familial gastric cancer is a new disease for which prophylactic surgery must be considered. The morbidity of this operation is much higher than that for other genetic diseases, but the alternative is a mortality risk of more than 80% at a young age. (Surgery 2001;130:612-9.)

Section snippets

Clinical history

Four patients in 1 family (B) and 2 in another (D) underwent prophylactic total gastrectomy after detailed analysis of family pedigree and careful counseling. Each family had a pattern of autosomal dominant inheritance of diffuse gastric cancer that could be documented over 4 generations. In 1 of these families, 2 out of 12 members in 4 generations who by pedigree analysis were found to be carriers of the mutation lived to advanced ages without developing gastric cancer and died of other

Results

All patients recovered uneventfully and were discharged at an average of 7 days postoperatively. The only perioperative complication was septic phlebitis at an intravenous site in 1 patient, which prolonged hospitalization for 3 days.

One patient with a hand-sewn anastomosis developed an esophageal stricture, which required multiple pneumatic dilatations in the first 6 postoperative months. Although he remains symptomatic, he has not needed dilatations for several months and is able to

Discussion

The performance of prophylactic total gastrectomy represents a new level of risk for patients with genetically defined disease. Some surgeons may be critical of performing a surgical procedure that carries a significant morbidity and mortality in asymptomatic healthy patients. Nevertheless, the risk of death at an early age from gastric cancer is extremely high when there is a clear family pedigree of autosomal dominant inheritance and the presence of E-cadherin gene mutations. Therefore, the

Summary

A rare but relatively well-defined syndrome of hereditary diffuse gastric cancer has been identified in the last few years that is associated with autosomal dominant inheritance, mutations in the E-cadherin (CDH1) gene, high penetrance of the gene (70% to 80%), onset of cancer at an early age (average, 38 years14), and a consistent pathologic type of diffuse gastric cancer (linitis plastica). This syndrome is analogous genetically to breast carcinoma associated with BRCA1 and medullary thyroid

Discussion

Dr Thomas A. Stellato (Cleveland, Ohio). Dr Lewis and his colleagues have presented a relatively rare disease, hereditary diffuse gastric cancer, with 21st century implications. The disease can be adequately managed through the coordinated efforts of geneticists, molecular biologists, and surgeons. Once a family is suspected of having familial gastric cancer, screening for the presence of E-cadherin gene mutations can identify the overwhelming majority of patients whose only effective treatment

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Reprint requests: Frank R. Lewis, MD, 2799 West Grand Blvd, Detroit, MI 48202.

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