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

  • Gastrointestinal Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

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.

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Authors and Affiliations

  1. Departments of Surgery, Stanford University School of Medicine, Stanford Comprehensive Cancer Center, Stanford, CA, USA

    Yijun Chen MD, James Rosing MD & Jeffrey A. Norton MD

  2. Departments of Pathology, Stanford University School of Medicine, Stanford Comprehensive Cancer Center, Stanford, CA, USA

    Teri A. Longacre MD

  3. Departments of Gastroenterology, Stanford University School of Medicine, Stanford Comprehensive Cancer Center, Stanford, CA, USA

    Jacques Van Dam MD

  4. Departments of Radiology, Stanford University School of Medicine, Stanford Comprehensive Cancer Center, Stanford, CA, USA

    R. Brooke Jeffrey MD & Teri A. Longacre MD

  5. Departments of Medicine, Stanford University School of Medicine, Stanford Comprehensive Cancer Center, Stanford, CA, USA

    Kerry Kingham MS, James M. Ford MD, Nicki Chun MS & Allison Kurian MD, MSc

  6. Departments of Genetics, Stanford University School of Medicine, Stanford Comprehensive Cancer Center, Stanford, CA, USA

    Kerry Kingham MS, James M. Ford MD & Nicki Chun MS

Authors
  1. Yijun Chen MD
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  2. Kerry Kingham MS
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  3. James M. Ford MD
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  4. James Rosing MD
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  5. Jacques Van Dam MD
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  6. R. Brooke Jeffrey MD
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  7. Teri A. Longacre MD
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  8. Nicki Chun MS
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  9. Allison Kurian MD, MSc
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  10. Jeffrey A. Norton MD
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Corresponding author

Correspondence to Jeffrey A. Norton MD.

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Chen, Y., Kingham, K., Ford, J.M. et al. A Prospective Study of Total Gastrectomy for CDH1-Positive Hereditary Diffuse Gastric Cancer. Ann Surg Oncol 18, 2594–2598 (2011). https://doi.org/10.1245/s10434-011-1648-9

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  • DOI: https://doi.org/10.1245/s10434-011-1648-9

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