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Annals of Surgical Oncology

, Volume 18, Issue 9, pp 2594–2598 | Cite as

A Prospective Study of Total Gastrectomy for CDH1-Positive Hereditary Diffuse Gastric Cancer

  • Yijun Chen
  • Kerry Kingham
  • James M. Ford
  • James Rosing
  • Jacques Van Dam
  • R. Brooke Jeffrey
  • Teri A. Longacre
  • Nicki Chun
  • Allison Kurian
  • Jeffrey A. NortonEmail author
Gastrointestinal Oncology

Abstract

Background

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer syndrome. Up to 30% of families with HDGC have mutations in the E-cadherin gene, CDH1. The role of prophylactic versus therapeutic gastrectomy for HDGC was studied prospectively.

Methods

Eighteen consecutive patients with CDH1 mutations and positive family history were studied prospectively, including 13 without and 5 with symptoms. Proportions were compared by Fisher’s exact test, and survival by the Breslow modification of the Wilcoxon rank-sum test.

Results

Each patient underwent total gastrectomy (TG), and 17 (94%) were found to have signet ring cell adenocarcinoma. Twelve of 13 asymptomatic patients had T1, N0 cancer, and only 2/12 (16%) had it diagnosed preoperatively despite state-of-the-art screening methods. Each asymptomatic patient did well postoperatively, and no patient has recurred. For five symptomatic patients, each (100%) was found to have signet ring cell adenocarcinoma (P = 0.002 versus asymptomatic) by preoperative endoscopy; three (60%) had lymph node involvement and two (40%) had distant metastases at time of operation. Two-year survival was 100% for asymptomatic and 40% for symptomatic patients (P < 0.01).

Conclusion

The data show that asymptomatic patients with family history of HDGC and CDH1 mutation have high probability of having signet ring cell adenocarcinoma of the stomach that is not able to be diagnosed on endoscopy; when symptoms arise, the diagnosis can be made by endoscopy, but they have metastases and decreased survival. Surveillance endoscopy is of limited value, and prophylactic gastrectomy (PG) is recommended for patients with family history of HDGC and CDH1 mutations.

Keywords

Gastric Cancer Total Gastrectomy Signet Ring Cell Hereditary Diffuse Gastric Cancer CDH1 Mutation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Society of Surgical Oncology 2011

Authors and Affiliations

  • Yijun Chen
    • 1
  • Kerry Kingham
    • 5
    • 6
  • James M. Ford
    • 5
    • 6
  • James Rosing
    • 1
  • Jacques Van Dam
    • 3
  • R. Brooke Jeffrey
    • 4
  • Teri A. Longacre
    • 2
    • 4
  • Nicki Chun
    • 5
    • 6
  • Allison Kurian
    • 5
  • Jeffrey A. Norton
    • 1
    Email author
  1. 1.Departments of SurgeryStanford University School of Medicine, Stanford Comprehensive Cancer CenterStanfordUSA
  2. 2.Departments of PathologyStanford University School of Medicine, Stanford Comprehensive Cancer CenterStanfordUSA
  3. 3.Departments of GastroenterologyStanford University School of Medicine, Stanford Comprehensive Cancer CenterStanfordUSA
  4. 4.Departments of RadiologyStanford University School of Medicine, Stanford Comprehensive Cancer CenterStanfordUSA
  5. 5.Departments of MedicineStanford University School of Medicine, Stanford Comprehensive Cancer CenterStanfordUSA
  6. 6.Departments of GeneticsStanford University School of Medicine, Stanford Comprehensive Cancer CenterStanfordUSA

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