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Endoscopy
DOI: 10.1055/a-2634-7895
Innovations and brief communications

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

Lianlian Wu
1   Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2152)
,
Judith Honing
2   gastroenterology, Erasmus mc, rotterdam, Netherlands
,
Anjui Wu
1   Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2152)
,
Sonia S Kupfer
3   Hepatology and Nutrition, The University of Chicago, Chicago, United States (Ringgold ID: RIN2462)
,
Tanya M. Bisseling
4   Department of Gastroenterology and Hepatology, Radboud umc, Nijmegen, Netherlands
5   Department of Pathology, Radboud umc, Nijmegen, Netherlands
,
Jolanda M van Dieren
6   Gastrointestinal oncology, the Netherlands Cancer Institute, Amsterdam, Netherlands
,
W. Keith Tan
1   Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2152)
,
Colin Y C Lee
1   Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2152)
,
Andreas V. Hadjinicolaou
7   Division of Gastroenterology and Hepatology, Department of Medicine, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2153)
8   Early Cancer Institute, Department of Oncology, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2152)
,
Yuan Huang
9   Department of applied mathematics and theoretical physics, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2152)
10   Department of Medicine, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2152)
,
Juan de la Revilla Negro
11   Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2153)
,
Mohmmed Tauseef Sharip
11   Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2153)
,
Joshua Elias
11   Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2153)
,
Hui Jun Lim
1   Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2152)
,
Nandini Karthik
1   Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2152)
,
Greta Markert
12   Cancer Research UK Cambridge, Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN92690)
,
William Prew
12   Cancer Research UK Cambridge, Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN92690)
,
Maria O’Donovan
13   Department of Histopathology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2153)
,
Marc Tischkowitz
14   Department of Medical Genetics, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2152)
,
Vijayendran Sujendran
15   Cambridge Oesophagus-gastric Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2153)
,
J Robert O'Neill
15   Cambridge Oesophagus-gastric Centre, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2153)
,
Florian Markowetz
12   Cancer Research UK Cambridge, Cancer Research UK Cambridge Research Institute, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN92690)
,
Rebecca C Fitzgerald
1   Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2152)
,
Massimiliano di Pietro
1   Early Cancer Institute, University of Cambridge, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2152)
16   Digestive Diseases, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom of Great Britain and Northern Ireland (Ringgold ID: RIN2153)
› Author Affiliations
Supported by: Addenbrookes Charitable Trust 300132
Supported by: Medical Research Council G111260
Supported by: Cancer Research UK EDDPJT-Nov23/100006
› Further Information
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Background and study aims Prophylactic total gastrectomy (PTG) is the definitive treatment for hereditary diffuse gastric cancer syndrome (HDGC). Endoscopic surveillance informs the requirement and optimal timing to surgery. However, endoscopic recognition of early signet ring cell carcinoma (SRCC) remains challenging. We aim to develop an endoscopic framework to optimise SRCC assessment during HDGC surveillance. Patient and methods We retrospectively analysed data from 147 HDGC individuals undergoing endoscopic surveillance to evaluate the diagnostic accuracy of endoscopic Cambridge criteria,We used machine learning to develop a clinical decision tree (cDT) to guide the application of Cambridge criteria. We then prospectively validated cDT in 66 CDH1 pathogenic-variant carriers. The inter-observer agreement and diagnostic accuracy of Cambridge criteria and cDT were assessed through multi-reader multi-case study. Results Retrospective analysis of 537 endoscopies showed 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 are independent predictors of higher cancer burden in HDGC individuals. In prospective study, cDT had 77.8% (21/27) sensitivity and 90.7% (49/54) specificity and improved performance of both experts and non-experts. Conclusion We developed and validated a practical endoscopic framework to enhance SRCC assessment during HDGC endoscopic surveillance.



Publication History

Received: 17 February 2025

Accepted after revision: 12 June 2025

Accepted Manuscript online:
12 June 2025

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