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Prospective cohort study assessing outcomes of patients from families fulfilling criteria for hereditary diffuse gastric cancer undergoing endoscopic surveillance.

AbstractBACKGROUND:
Prophylactic total gastrectomy is performed in hereditary diffuse gastric cancer (HDGC) patients carrying the CDH1 mutation because endoscopic surveillance often fails to detect microscopic disease.
OBJECTIVE:
The aim of this study was to determine the natural history and outcomes of patients with HDGC undergoing endoscopy.
DESIGN:
Prospective, cohort observational study.
SETTINGS:
Tertiary referral center.
PATIENTS:
Patients fulfilling criteria for HDGC who opted to undergo endoscopy.
INTERVENTION:
Research surveillance program using high-resolution white-light endoscopy with autofluorescence and narrow-band imaging combined with targeted and multiple random biopsies assessed by an expert histopathologist for the presence of signet ring cell carcinoma.
MAIN OUTCOME MEASUREMENTS:
The primary endpoint was the endoscopic yield of microscopic signet ring cell carcinoma according to patient mutation status and subsequent decision to undergo surgery. The secondary endpoint was the additional yield of targeted biopsies compared with random biopsies.
RESULTS:
Between September 2007 and March 2013, 29 patients from 17 families underwent 70 surveillance endoscopies. Signet ring cell carcinoma foci were identified in 14 of 22 (63.6%) patients with confirmed CDH1 germline mutations and 2 of 7 (28.6%) with no pathogenic mutation identified. Eleven of 16 (9 CDH1-positive) patients proceeded to gastrectomy in a median 5.7 months. Five patients delayed surgery. In 1 patient, advanced gastric cancer developed 40.2 months after the first endoscopic findings.
LIMITATIONS:
No control group.
CONCLUSIONS:
Careful white-light examination with targeted and random biopsies combined with detailed histopathology can identify early lesions and help to inform decision making with regard to gastrectomy. Autofluorescence and narrow-band imaging are of limited utility. Delaying gastrectomy in individuals with signet ring cell carcinoma foci carries a high risk and has to be weighed carefully.
AuthorsYean Cheant Lim, Massimiliano di Pietro, Maria O'Donovan, Susan Richardson, Irene Debiram, Susan Dwerryhouse, Richard H Hardwick, Marc Tischkowitz, Carlos Caldas, Krish Ragunath, Rebecca C Fitzgerald
JournalGastrointestinal endoscopy (Gastrointest Endosc) Vol. 80 Issue 1 Pg. 78-87 (Jul 2014) ISSN: 1097-6779 [Electronic] United States
PMID24472763 (Publication Type: Journal Article, Observational Study, Research Support, Non-U.S. Gov't, Video-Audio Media)
CopyrightCopyright © 2014 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.
Chemical References
  • Antigens, CD
  • Biomarkers, Tumor
  • CDH1 protein, human
  • Cadherins
  • Genetic Markers
Topics
  • Adult
  • Aged
  • Antigens, CD
  • Biomarkers, Tumor (genetics)
  • Biopsy
  • Cadherins (genetics)
  • Carcinoma, Signet Ring Cell (genetics, pathology, surgery)
  • Female
  • Follow-Up Studies
  • Gastrectomy
  • Gastroscopy (methods)
  • Genetic Markers
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Middle Aged
  • Narrow Band Imaging
  • Outcome Assessment, Health Care
  • Prospective Studies
  • Stomach (pathology, surgery)
  • Stomach Neoplasms (genetics, pathology, surgery)

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