Prophylactic total gastrectomy for familial gastric cancer

Background. An autosomal dominant syndrome of diffuse gastric cancer has be en reported with germline mutations in the E-cadherin (CDH1) gene and has b een identified in approximately 14 families and 50 individuals worldwide. P enetrance of the gene is 70% to 80%, and thr average age of onset of gastri c cancer is 37 years. These characteristics have led to the consideration o f prophylactic total gastrectomy in family members with CDH1 mutations. Methods. We report here the first use of prophylactic gastrectomy in 6 asym ptomatic 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 w as performed via an upper midline incision, and reconstruction of the gastr ointestinal tract was done via a Roux-en-Y esophagojejunostomy. Complete, r emoval of all gastric mucosa was documented intraoperatively, and confirmat ion 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 patient s 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 mu ltiple 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.