Clinical decision tree for optimizing endoscopic assessment of signet ring cell carcinoma in hereditary diffuse gastric cancer surveillance.

Journal: Endoscopy
Published Date: Jul 30, 2025

Abstract

Prophylactic total gastrectomy is the definitive treatment for hereditary diffuse gastric cancer syndrome (HDGC). Endoscopic surveillance informs the requirement for and optimal timing of surgery. However, endoscopic recognition of early signet ring cell carcinoma (SRCC) remains challenging. We developed an endoscopic framework to optimize SRCC assessment during HDGC surveillance.We retrospectively analyzed data from 147 individuals with HDGC undergoing endoscopic surveillance to evaluate the diagnostic accuracy of the endoscopic Cambridge criteria. We used machine learning to develop a clinical decision tree (cDT) to guide the application of the Cambridge criteria. We then prospectively validated the cDT in 66 CDH1 pathogenic-variant carriers. The interobserver agreement and diagnostic accuracy of the Cambridge criteria and cDT were assessed through a multi-reader multi-case study.Retrospective analysis of 537 endoscopies showed that the Cambridge criteria achieved 82.8% (48/58) sensitivity and 78.2% (140/179) specificity for SRCC diagnosis. The presence and number of neoplastic pale areas were independent predictors of higher cancer burden in HDGC individuals. In the prospective study, cDT had 77.8% (21/27) sensitivity and 90.7% (49/54) specificity, and improved performance of both experts and non-experts.We developed and validated a practical endoscopic framework for enhancing SRCC assessment during HDGC endoscopic surveillance.

Authors

  • Lianlian Wu
    Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, China.
  • Judith Honing
    gastroenterology, Erasmus mc, rotterdam, Netherlands.
  • Anjui Wu
    Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland.
  • Sonia S Kupfer
    Department of Medicine, The University of Chicago, Chicago, Illinois, United States of America.
  • Tanya M Bisseling
    Department of Gastroenterology and Hepatology, Radboud umc, Nijmegen, Netherlands.
  • Jolanda M van Dieren
    Gastrointestinal oncology, the Netherlands Cancer Institute, Amsterdam, Netherlands.
  • W Keith Tan
    Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland.
  • Colin Y C Lee
    Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland.
  • Andreas V Hadjinicolaou
    Division of Gastroenterology and Hepatology, Department of Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom of Great Britain and Northern Ireland.
  • Yuan Huang
    School of Electrical Engineering and Information, Sichuan University, Chengdu 610065, China.
  • Juan de la Revilla Negro
    Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom of Great Britain and Northern Ireland.
  • Mohmmed Tauseef Sharip
    Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom of Great Britain and Northern Ireland.
  • Joshua Elias
    Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom of Great Britain and Northern Ireland.
  • Hui Jun Lim
    Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland.
  • Nandini Karthik
    Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland.
  • Greta Markert
    Cancer Research UK Cambridge, Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom of Great Britain and Northern Ireland.
  • William Prew
    Cancer Research UK Cambridge, Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom of Great Britain and Northern Ireland.
  • Maria O'Donovan
    MRC Cancer Unit, University of Cambridge, Cambridge, UK.
  • Marc Tischkowitz
    Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland.
  • Vijayendran Sujendran
    Cambridge Oesophagus-gastric Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom of Great Britain and Northern Ireland.
  • J Robert O'Neill
    Cambridge Oesophagus-gastric Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom of Great Britain and Northern Ireland.
  • Florian Markowetz
    Cancer Research UK Cambridge Centre, University of Cambridge, Cambridge CB2 0RE, UK; Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge CB2 0RE, UK. Electronic address: florian.markowetz@cruk.cam.ac.uk.
  • Rebecca C Fitzgerald
    MRC Cancer Unit, University of Cambridge, Cambridge, United Kingdom.
  • Massimiliano di Pietro
    Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland.

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