Enhanced endoscopic detection of occult gastric cancer in carriers of pathogenic CDH1 variants
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ORIGINAL ARTICLE—ALIMENTARY TRACT
Enhanced endoscopic detection of occult gastric cancer in carriers of pathogenic CDH1 variants Bryan Franklin Curtin1,2 • Lauren Ann Gamble3 • Samuel Ali Schueler1 Samantha Marilyn Ruff3 • Martha Quezado4 • Markku Miettinen4 • Grace-Ann Fasaye5 • Monica Passi1 • Jonathan Matthew Hernandez3 • Theo Heller1 • Christopher Koh1 • Jeremy Lee Davis3
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Received: 4 August 2020 / Accepted: 2 November 2020 Ó This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2020
Abstract 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%, Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00535-020-01749-w) contains supplementary material, which is available to authorized users.
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. Keywords Hereditary cancer syndromes Endoscopy Cancer early detection Gastric cancer
& Jeremy Lee Davis [email protected] 1
Digestive Disease Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
2
Division of Gastroenterology and Motility, Mercy Medical Center, Baltimore, MD, USA
3
Surgical Oncology Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA
4
Laboratory of Pathology, N
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