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Crescent City GI Update 2018 Ochsner Clinic, NOLA Optimizing Endoscopic Evaluation of Barrett s Esophagus What Should I Do in My Practice? Gregory G. Ginsberg, M.D. Professor of Medicine University of Pennsylvania Perelman School of Medicine Gastroenterology Division Executive Director of Endoscopic Services Penn Medicine and Abramson Cancer Center 20 min Learning Objectives: At the conclusion of this presentation, the participant should be able to: Discuss the latest publications that support screening and surveillance in BE Appreciate the nuances of dysplasia detection and confirmation Optimize endoscopic evaluation of BE 1

Barrett s Esophagus Replacement of normal squamous mucosa Specialized Intestinal Metaplasia (SIM) Response to chronic GE-reflux Endoscopically recognizable Biopsy confirmed Why Do We Care About Barrett s Esophagus? BE is common, 3-13% general population Adeno CA Esophagus & EG-J Most, if not all, associated with Barrett s 30 to 125-fold increase cancer risk 0.1% to 0.5% per year cancer risk Metaplasia Dysplasia Carcinoma Opportunity for screening, surveillance, and early detection Progression to cancer is preventable with intervention Spechler & Souza. NEJM 2014;371:836-845 2

Esophageal Adenocarcinoma Sequence Acid Reflux Barrett s Intervention? LGD Intervention? HGD Intervention IMCA Intervention Invasive Ca Esophageal Adenocarcinoma and Barrett s Esophagus Poor prognosis, 15% 5-yr survival Symptomatic presentation coincides with advanced stage disease 1 in 400 people with BE in the USA develops EAC each year <5% of patients undergoing resection for EAC have a previous diagnosis of BE 3

Is Screening and Surveillance for BE Effective? There are no accurate, cost-effective, minimally invasive techniques available to screen for BE Screening for and surveillance of BE have not been proven to prevent death due to EAC While most authorities and GI professional societies believe that screening and surveillance are effective we ve had a hard time proving it! Who to screen for BE? Chronic GERD 15% Central obesity Smoking Make gender White race Hiatal hernia Age > 50 Enriched population Effective acid suppression therapy Careful HDWL and NBI exam Biopsy tissue sampling If negative, no further surveillance 4

Cohort study of patients with BE in the VAMC hospitals during 2004 2009 Excluded those with conditions that affect overall survival Identified those diagnosed with EAC after BE diagnosis through 2011 Conducted chart reviews to identify BE surveillance program Indication for endoscopy at EAC diagnosis Verify diagnosis, stage, therapy and cause of death El-Serag HB, et al. Gut 2016;65:1252 1260 Examined the association between surveillance indication for EAC diagnosis with or without surveillance program and EAC stage and treatment receipt in logistic regression models, and with time to death or cancer-related death using a Cox proportional hazards regression model. 5

Among 29,536 patients with BE, 424 patients developed EAC during a mean follow-up of 5.0 years. Of those, 209 (49.3%) patients were diagnosed as a result of BE surveillance endoscopy El-Serag HB, et al. Gut 2016;65:1252 1260 Compared to patients diagnosed by non-be surveillance endoscopy these patients were more likely to: Be diagnosed at an early stage Receive esophagectomy Survive longer Have lower cancer-related mortality El-Serag HB, et al. Gut 2016;65:1252 1260 6

El-Serag HB, et al. Gut 2016;65:1252 1260 The reduction in cancer-related death was largely explained by the early stage of EAC at the time of diagnosis. Success of Endoscopic Therapy Enhances the Utility of BE Screening and Surveillance Further reduce the development of advanced EAC 7

Surveillance: ACG Guidelines Dysplasia Documentation Follow-up Management None 2 EGD w/ biopsy (1 yr apart) 3 5 year EGD to detect progression Surveillance Low-Grade Highest grade on repeat (determines time of next EGD) EGD Q 6-12 mo to detect progression Surveillance High-Grade Pathologist Confirmation Repeat EGD w/ biopsy Rule out cancer EGD Q 3 mo to detect progression Intervention Surveillance Esophagectomy Intervention EMR/Ablation Wang KK, Sampliner RE. Am J. Gastro 2008. The Goal of Surveillance is to Detect Dysplasia Non-dysplastic BE Low grade dysplasia High grade dysplasia Early cancer 8

How well are we doing with surveillance? Meta-analysis of 24 studies reporting on 820 missed and incident EACs 25.3% were classified as missed (95% CI) 74.7% as incident EACs (95% CI) When the analysis was restricted to nondysplastic BE cohorts (15 studies) 23.9% of EACs were classified as missed (95% CI). Meta-analysis of 10 studies with follow-up periods of 5 years (a total of 239 EACs) 22.0% were classified as missed (95% CI) 9

Can we do a better job at surveillance? How Do We Detect Dysplasia? Effective acid suppression Careful HD white light exam With the eyes of an experienced operator Electronic enhanced imaging Targeted >> random tissue sampling Diagnostic EMR Second opinion by pathology expert or consensus expert review Early repeat exam for uncertainty 10

Over-diagnosis dilemma Reactive changes or HGD? Erosive esophagitis? Review pathology by expert in this field Repeat biopsies after highdose PPI Barrett s Inspection Time (BIT) Longer BIT led to more HGD/EAC detection (p=0.001) despite no difference in BE length (p=0.10) Gupta N et al. DDW 2011 11

NBI Principles Short Wavelength Shallow imaging Long Wavelength Deep imaging White light illumination WLE Narrow band illumination NBI Filters peak Hgb absorption spectra Enhanced vascular pattern 12

Barrett s Detection WLE NBI NBI with Magnification 1. Irregular/disrupted mucosal patterns BE with HGD/EC WLE NBI 2. Irregular vascular patterns 3. Abnormal blood vessels Kara MA. GIE 2006;64:155 100% sites > one feature 85% sites > 2 features 13

Barrett s International NBI Group (BING) aimed to develop and validate an NBI classification system for identification of dysplasia and cancer in patients with BE When images are assessed with a high degree of confidence, the system can classify BE with >90% accuracy and a high level of interobserver agreement 14

Dysplasia Detection BE 1 Importance of a Careful Exam in All Cases 15

Endoluminal Resection (ELR) for Focal HGD/ImCa ELR for Accurate Diagnosis, and Staging and Definitive Therapy Pathology: Moderately differentiated adenocarcinoma, confined to the lamina propria, without lymphovascular invasion; intestinal metaplasia with HGD 16

ELR for Barrett s HGD/ImCa Focal macroscopically distinguishable lesions Provides specimen for histological inspection Depth of invasion Margins of resection Degree of differentiation Lymphovascular invasion Accurate staging Upgrade dysplasia ~40% Ahmad et al. GIE 2002;55:390-396. Nijhawan & Wang. GIE 2000;52:328-332. Cap-Assistant Surveillance Endoscopy 17

Optimizing Endoscopic Evaluation of Barrett s Esophagus What Should I Do in My Practice? Screen at-risk individuals who are apt to benefit from surveillance Surveillance at 1, 3 and 5-year intervals Use HDWL and NBI with targeted biopsies Cleanse and variably distend the esophagus Take your time Incorporate the BING classification Use a cap 18