Central Surgical AssociationProphylactic total gastrectomy for familial gastric cancer*
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
References (21)
Predisposition to cancer in the Bonaparte family
Am J Surg
(1938)- et al.
Familial gastric polyposis revisited: autosomal dominant inheritance confirmed
Cancer Genet Cytogenet
(1991) - et al.
Diffuse type gastric and lobular breast carcinoma in a familial gastric cancer patient with an E-cadherin germline mutation
Am J Pathol
(1999) Familial gastric cancer
N Z Med J
(1964)- et al.
Genetic etiology of gastric carcinoma
Genet Epidemiol
(1986) - et al.
Hereditary linitis plastica of the stomach
Am J Gastroenterol
(1995) - et al.
E-cadherin gene mutations provide clues to diffuse type gastric carcinomas
Cancer Res
(1994) - et al.
Inactivation of the E-cadherin gene in primary gastric carcinomas and gastric carcinoma cell lines
Jpn J Cancer Res
(1996) - et al.
E-cadherin gene mutations in signet ring cell carcinoma of the stomach
Jpn J Cancer Res
(1996) - et al.
E-cadherin germline mutations in familial gastric cancer
Nature
(1998)
Cited by (131)
Global distribution of prophylactic total gastrectomy in E-cadherin (CDH1) mutations
2022, Seminars in OncologyHereditary diffuse gastric cancer (HDGC). An overview
2022, Clinics and Research in Hepatology and GastroenterologyHereditary gastric cancer: Challenges for the pathologist in 2020
2020, Annales de PathologieTotal Gastrectomy for CDH-1 Mutation Carriers: An Institutional Experience
2020, Journal of Surgical ResearchCitation Excerpt :The postsurgical patient experience includes anticipated eating difficulty, weight loss, and occasional dumping syndrome. Previous studies have reported a range of 10-21 kg or 13-25% weight loss between 5 and 10 mo after the prophylactic total gastrectomy.12,14,16,17,25 Our series utilizes a jejunal pouch reconstruction, which allows for improved eating with an anatomic reservoir.
Cancer of the Stomach
2019, Abeloff’s Clinical Oncology
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Reprint requests: Frank R. Lewis, MD, 2799 West Grand Blvd, Detroit, MI 48202.