E0691 - Diagnostic Yield of Endoscopic Screening for Identification of Signet Ring Cell in Carriers of a Pathogenic Variant in CDH1

Lady Katherine MejiaPerez, MD¹, Margaret M. O'Malley, ¹, Arjun Chatterjee, MD¹, Lisa LaGuardia, ¹, Susan Milicia, RN², Sarah McGee, MS², Joshua Sommovilla, MD¹, Nicholas Smith, MD², David Liska, MD², Carole Macaron, MD¹, Matthew Walsh, MD², Carol A. Burke, MD, FACG^2
1Cleveland Clinic Foundation, Cleveland, OH; ²Cleveland Clinic, Cleveland, OH

Introduction: Individuals with pathogenic variants (PV) in CDH1 are at high risk of hereditary diffuse gastric cancer (HDGC). Pre-operative upper endoscopy (EGD) using the Cambridge protocol (CP) to detect signet ring cells (SRC) and annual EGD in those deferring prophylactic total gastrectomy (TG) is recommended. The recently reported yield for pre-op detection of SCR by CP (30-minute exam of the gastric mucosa with targeted biopsy of pale patches and 30 random biopsies throughout the stomach) compared to the “Bethesda” protocol (targeted biopsy and 88 random biopsies) was 15% versus 36% of patients, respectively. Our aim was to describe the diagnostic yield of EGD surveillance in our center for preoperative detection of SRC in asymptomatic CDH1 carriers.

Methods: Single-center, retrospective cohort study. Included patients with CDH1 PVs who underwent ≥ 1 EGD for HDGC surveillance at Cleveland Clinic between 2007-2022. Our EGD biopsy protocol evolved from CP to include targeted biopsy and 77 random biopsies of the stomach. Our primary outcome was to determine the accuracy of endoscopic biopsy to detect SRC preoperatively in patients undergoing TG.

Results: 61 carriers of CDH1 from 39 families were identified. 12 were excluded (presented with symptomatic cancer, or not in surveillance program). 49 patients [68% female, mean age at 1^st EGD 45 years] underwent 1 to 8 EGDs for a total of 101 EGDs [table]. One endoscopist did 83% of all exams. Mean procedural time was 29 minutes [IQR 24-35]. Twenty-four patients (49%) underwent TG. 21/ 24 (87.5%) had SRC detected in TG specimen and all at early stage. 16/21 (76%) were diagnosed by endoscopic biopsy prior to TG. Of the 5 patients without preoperative endoscopic detection of SRC, 3 had no SRC in the TG specimen. SRC were distributed in the fundus, antrum, body and cardia equally. No recurrent disease has been found during a mean follow-up of 1.5 years. The 37 patients without SRC that did not undergo PTG are recommended to undergo EGD every 12 months and have had a mean follow-up of 2.8 years with no advanced stage or symptomatic cancer.

Discussion: Nearly 90% of asymptomatic patients with PV in CDH1 had SRC detected on TG and all detected at early stage. Our protocol with ≥77 biopsies had higher yield for identification of SRC higher than protocols with fewer biopsies but did not detect SRC preoperatively in 24% of patients. Novel approaches to enhance SRC detection and timing of TG are needed.






Disclosures:


Lady Katherine MejiaPerez, MD¹, Margaret M. O'Malley, ¹, Arjun Chatterjee, MD¹, Lisa LaGuardia, ¹, Susan Milicia, RN², Sarah McGee, MS², Joshua Sommovilla, MD¹, Nicholas Smith, MD², David Liska, MD², Carole Macaron, MD¹, Matthew Walsh, MD², Carol A. Burke, MD, FACG². E0691 - Diagnostic Yield of Endoscopic Screening for Identification of Signet Ring Cell in Carriers of a Pathogenic Variant in CDH1, ACG 2022 Annual Scientific Meeting Abstracts. Charlotte, NC: American College of Gastroenterology.