Yean Cheant Lim1, Massimiliano di Pietro2, Maria O'Donovan3, Susan Richardson4, Irene Debiram4, Susan Dwerryhouse5, Richard H Hardwick5, Marc Tischkowitz6, Carlos Caldas2, Krish Ragunath7, Rebecca C Fitzgerald2. 1. Department of Gastroenterology, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom. 2. MRC Cancer Unit, Hutchison-MRC Research Centre, Cambridge, United Kingdom. 3. Department of Histopathology, Cambridge University Hospitals NHS Trust, University of Cambridge, Cambridge, United Kingdom. 4. Familial Gastric Cancer Registry, University Department of Oncology, Cambridge, United Kingdom. 5. Department of Oesophago-Gastric Surgery, Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom. 6. Department of Medical Genetics, University of Cambridge and Cambridge University Hospitals NHS Trust, Cambridge, United Kingdom. 7. Nottingham Digestive Diseases Centre, Nottingham, United Kingdom.
Abstract
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. DESIGN: Prospective, cohort observational study. SETTINGS: Tertiary referral center. PATIENTS: Patients fulfilling criteria for HDGC who opted to undergo endoscopy. INTERVENTION: 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. MAIN OUTCOME MEASUREMENTS: 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. LIMITATIONS: 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.
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. DESIGN: Prospective, cohort observational study. SETTINGS: Tertiary referral center. PATIENTS: Patients fulfilling criteria for HDGC who opted to undergo endoscopy. INTERVENTION: 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. MAIN OUTCOME MEASUREMENTS: 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. LIMITATIONS: 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.
Authors: Apostolos Pappas; Wei Keith Tan; William Waldock; Susan Richardson; Monika Tripathi; Wladyslaw Januszewicz; Geoffrey Roberts; Maria O'Donovan; Rebecca C Fitzgerald; Massimiliano di Pietro Journal: Endoscopy Date: 2020-07-17 Impact factor: 10.093
Authors: Nina Hallowell; Shirlene Badger; Sue Richardson; Carlos Caldas; Richard H Hardwick; Rebecca C Fitzgerald; Julia Lawton Journal: Fam Cancer Date: 2016-10 Impact factor: 2.375
Authors: Samuel A Schueler; Lauren A Gamble; Bryan F Curtin; Samantha M Ruff; Maureen Connolly; Cathleen Hannah; Martha Quezado; Markku Miettinen; Maureen George; Andrew M Blakely; Jonathan M Hernandez; Theo Heller; Christopher Koh; Jeremy L Davis Journal: J Gastrointest Oncol Date: 2021-04
Authors: Rachel S van der Post; Ingrid P Vogelaar; Fátima Carneiro; Parry Guilford; David Huntsman; Nicoline Hoogerbrugge; Carlos Caldas; Karen E Chelcun Schreiber; Richard H Hardwick; Margreet G E M Ausems; Linda Bardram; Patrick R Benusiglio; Tanya M Bisseling; Vanessa Blair; Eveline Bleiker; Alex Boussioutas; Annemieke Cats; Daniel Coit; Lynn DeGregorio; Joana Figueiredo; James M Ford; Esther Heijkoop; Rosella Hermens; Bostjan Humar; Pardeep Kaurah; Gisella Keller; Jennifer Lai; Marjolijn J L Ligtenberg; Maria O'Donovan; Carla Oliveira; Hugo Pinheiro; Krish Ragunath; Esther Rasenberg; Susan Richardson; Franco Roviello; Hans Schackert; Raquel Seruca; Amy Taylor; Anouk Ter Huurne; Marc Tischkowitz; Sheena Tjon A Joe; Benjamin van Dijck; Nicole C T van Grieken; Richard van Hillegersberg; Johanna W van Sandick; Rianne Vehof; J Han van Krieken; Rebecca C Fitzgerald Journal: J Med Genet Date: 2015-05-15 Impact factor: 6.318
Authors: Robert Hüneburg; Tim Marwitz; Peer van Heteren; Tobias J Weismüller; Jonel Trebicka; Ronja Adam; Stefan Aretz; Alberto Perez Bouza; Dimitrios Pantelis; Jörg C Kalff; Jacob Nattermann; Cristian P Strassburg Journal: Endosc Int Open Date: 2016-08-31
Authors: Bryan Franklin Curtin; Lauren Ann Gamble; Samuel Ali Schueler; Samantha Marilyn Ruff; Martha Quezado; Markku Miettinen; Grace-Ann Fasaye; Monica Passi; Jonathan Matthew Hernandez; Theo Heller; Christopher Koh; Jeremy Lee Davis Journal: J Gastroenterol Date: 2020-11-18 Impact factor: 6.772