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


METHODS
Prospective, cohort observational study.


METHODS
Tertiary referral center.


METHODS
Patients fulfilling criteria for HDGC who opted to undergo endoscopy.


METHODS
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.


METHODS
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.


CONCLUSIONS
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.
Department of Gastroenterology, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom.
Yean Cheant
YC
Lim
MRC Cancer Unit, Hutchison-MRC Research Centre, Cambridge, United Kingdom.
Massimiliano
M
di Pietro
Department of Histopathology, Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, United Kingdom.
Maria
M
O'Donovan
Familial Gastric Cancer Registry, University Department of Oncology, Cambridge, United Kingdom.
Susan
S
Richardson
Familial Gastric Cancer Registry, University Department of Oncology, Cambridge, United Kingdom.
Irene
I
Debiram
Department of Oesophago-Gastric Surgery, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom.
Susan
S
Dwerryhouse
Department of Oesophago-Gastric Surgery, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom.
Richard H
RH
Hardwick
Department of Medical Genetics, University of Cambridge and Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom.
Marc
M
Tischkowitz
MRC Cancer Unit, Hutchison-MRC Research Centre, Cambridge, United Kingdom.
Carlos
C
Caldas
Nottingham Digestive Diseases Centre, Nottingham, United Kingdom.
Krish
K
Ragunath
MRC Cancer Unit, Hutchison-MRC Research Centre, Cambridge, United Kingdom.
Rebecca C
RC
Fitzgerald
D000328:Adult; D000368:Aged; D015703:Antigens, CD; D014408:Biomarkers, Tumor / Q000235:genetics; D001706:Biopsy; D015820:Cadherins / Q000235:genetics; D018279:Carcinoma, Signet Ring Cell / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D005743:Gastrectomy; D005773:Gastroscopy / Q000379:methods*; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D062048:Narrow Band Imaging; D017063:Outcome Assessment, Health Care; D011446:Prospective Studies; D013270:Stomach / Q000473:pathology* / Q000601:surgery; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology* / Q000601:surgery
D015703:Antigens, CD; D014408:Biomarkers, Tumor; C513384:CDH1 protein, human; D015820:Cadherins; D005819:Genetic Markers