Prophylactic Laparoscopic Total Gastrectomy for Hereditary Diffuse Gastric Cancer

Abstract

Introduction: Ten percent of gastric cancer (GC) cases are familial. Of the familial cases, one-third results from a mutation in the tumor suppressor gene CDH1, which normally encodes for a transmembrane protein, E-cadherin. The loss of E-cadherin leaves patients at high risk for developing diffuse gastric cancer. These individuals with 'hereditary diffuse gastric cancer' (HDGC) have a high mortality if early diagnosis is not made. Despite its clear genetic origin, optimal management of HDGC family members is controversial. The utility and efficacy of current cancer screening programs for mutation carriers are unproven, which has given credence to the recommendation for prophylactic gastrectomy. We report the first prophylactic laparoscopic total gastrectomy. Case Report: A 53 year-old Caucasian woman was referred to our clinic for a family history of gastric cancer. After an extensive pedigree analysis, it was apparent that her family had an autosomal dominant form of diffuse gastric cancer. The patient was asymptomatic, had no past medical history and her exam was unremarkable. She had the CDH1 gene mutation. Previous upper endoscopies with gastric biopsies were normal. After genetic counseling, she elected to undergo a prophylactic laparoscopic hand-assisted total gastrectomy. The gross specimen appeared normal. Microscopically there were 11 foci of invasive adenocarcinoma limited to the lamina propria in a background of diffuse (signet ring cell) adenocarcinoma in-situ. She had return of bowel function by day 3 and was discharged home on postoperative day 4. More than one-year after the surgery she is disease free and doing well. Discussion: Genomics is playing a greater role in clinical medicine, as exemplified by our case, in which a patient with a CDH1 mutation within a family of HDGC underwent prophylactic laparoscopic gastrectomy. Despite the normal-appearing stomach, there were many microscopic foci of adenocarcinoma. Thus, the surgery was curative. Our case highlights the importance of taking a thorough family history and obtaining a pedigree analysis. In addition, it is evident that endoscopic screening in HDGC cannot rule out diffuse GC, as the stomach and biopsies can be normal despite the presence of adenocarcinoma. Therefore, our case supports the recommendation for prophylactic gastrectomy in HDGC. Furthermore, we report that successful prophylactic gastrectomy can be accomplished laparoscopically.