Enhanced endoscopic detection of occult gastric cancer in carriers of pathogenic CDH1 variants.
Cancer early detection
Endoscopy
Gastric cancer
Hereditary cancer syndromes
Journal
Journal of gastroenterology
ISSN: 1435-5922
Titre abrégé: J Gastroenterol
Pays: Japan
ID NLM: 9430794
Informations de publication
Date de publication:
02 2021
02 2021
Historique:
received:
04
08
2020
accepted:
02
11
2020
pubmed:
19
11
2020
medline:
15
12
2021
entrez:
18
11
2020
Statut:
ppublish
Résumé
Germline inactivating variants in the CDH1 tumor suppressor gene impart an elevated lifetime risk of diffuse gastric cancer. The current endoscopic surveillance method depends upon random gastric biopsies for early cancer detection. Asymptomatic adults with pathogenic or likely pathogenic CDH1 variants referred for endoscopic gastric cancer surveillance were included in this retrospective cohort. Upper gastrointestinal endoscopy was performed according to the consensus Cambridge method, in the early period, or a systematic (Bethesda) protocol as part of an ongoing natural history study. The primary outcome measure was cancer detection. Collectively, 135 endoscopic surveillance procedures were performed in 120 patients. Twenty-six (19%, 26/135) procedures were performed using Cambridge method and 109 (81%) using the Bethesda protocol. Gastric signet ring cell carcinomas were detected in 15% (4/26) using the Cambridge method and 36% (40/109) using the Bethesda protocol (p < 0.05). Almost half (44.2%, 53/120) of patients later elected for prophylactic total gastrectomy, of whom 51 (96%, 51/53) had a signet ring cell carcinoma (T1a) discovered by histopathology. On a per endoscopy basis, the false-negative rates of detection using Cambridge method and Bethesda protocol were 80% (12/15) and 37.7% (17/45), respectively (p < 0.01). Gastric cancer detection was more frequent with implementation of a systematic surveillance protocol in CDH1 variant carriers. Given the decision for prophylactic surgery is often made by patients in the context of family history and pathologic result of surveillance biopsies, we propose the Bethesda protocol offers patients an opportunity to make more informed decisions.
Sections du résumé
BACKGROUND
Germline inactivating variants in the CDH1 tumor suppressor gene impart an elevated lifetime risk of diffuse gastric cancer. The current endoscopic surveillance method depends upon random gastric biopsies for early cancer detection.
METHODS
Asymptomatic adults with pathogenic or likely pathogenic CDH1 variants referred for endoscopic gastric cancer surveillance were included in this retrospective cohort. Upper gastrointestinal endoscopy was performed according to the consensus Cambridge method, in the early period, or a systematic (Bethesda) protocol as part of an ongoing natural history study. The primary outcome measure was cancer detection.
RESULTS
Collectively, 135 endoscopic surveillance procedures were performed in 120 patients. Twenty-six (19%, 26/135) procedures were performed using Cambridge method and 109 (81%) using the Bethesda protocol. Gastric signet ring cell carcinomas were detected in 15% (4/26) using the Cambridge method and 36% (40/109) using the Bethesda protocol (p < 0.05). Almost half (44.2%, 53/120) of patients later elected for prophylactic total gastrectomy, of whom 51 (96%, 51/53) had a signet ring cell carcinoma (T1a) discovered by histopathology. On a per endoscopy basis, the false-negative rates of detection using Cambridge method and Bethesda protocol were 80% (12/15) and 37.7% (17/45), respectively (p < 0.01).
CONCLUSIONS
Gastric cancer detection was more frequent with implementation of a systematic surveillance protocol in CDH1 variant carriers. Given the decision for prophylactic surgery is often made by patients in the context of family history and pathologic result of surveillance biopsies, we propose the Bethesda protocol offers patients an opportunity to make more informed decisions.
Identifiants
pubmed: 33206267
doi: 10.1007/s00535-020-01749-w
pii: 10.1007/s00535-020-01749-w
pmc: PMC9169699
mid: NIHMS1801997
doi:
Substances chimiques
Antigens, CD
0
CDH1 protein, human
0
Cadherins
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
139-146Subventions
Organisme : Intramural NIH HHS
ID : ZIA BC011861
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA DK075150
Pays : United States
Organisme : Intramural NIH HHS
ID : ZID BC011291
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIE BC011992
Pays : United States
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