Management of Barrett s Esophagus Lauren B. Gerson MD, MSc Associate Clinical Professor, UCSF Director of Clinical Research Gastroenterology Fellowship Program California Pacific Medical Center San Francisco, CA Case Presentation 71 year old Asian female on proton pump inhibitor therapy for non-specific chest pain Diagnosed with BE on initial endoscopy Pathology demonstrates intestinal metaplasia She undergoes yearly endoscopic examinations Copyright 2015 American College of Gastroenterology 1
71 year-old Asian Female What is the most likely diagnosis? i What is the best management strategy? What is this patient s risk of esophageal adenocarcinoma? Rubenstein AJG 2011 Definition of BE Sharma, Gastroenterology 2006 Copyright 2015 American College of Gastroenterology 2
2015 American College of Gastroenterology Barrett s Esophagus Guideline GRADE System for ACG Guidelines GRADE system (www.gradepro.org) Level of evidence High (implying that further research was unlikely to change the authors confidence in the estimate of the effect) Moderate (further research would be likely to have an impact on the confidence in the estimate of effect) Low (further research would be expected to have an important impact on the confidence in the estimate of the effect and would be likely to change the estimate). Strength of a recommendation Strong when the desirable effects of an intervention clearly outweigh the undesirable effects Conditional when there is uncertainty about the trade-offs Copyright 2015 American College of Gastroenterology 3
52 year-old Caucasian male with chronic GERD Symptoms > 5 years, BMI=32, Father with BE EGD with Prague C2M5 Pathology: non-dysplastic BE 4 cm hiatal hernia present Symptoms well-controlled on daily PPI He wants to know his risk of cancer and whether he should undergo surgery Management Questions What is his risk for esophageal adenocarcinoma? Should this patient remain on PPI therapy? Should you have him take daily aspirin? Would you recommend hiatal hernia repair? Would you perform radiofrequency ablation? What is the recommended surveillance protocol? Copyright 2015 American College of Gastroenterology 4
Risk of Cancer Based on Degree of Dysplasia Dysplasia Type Studies/Patie nts Incidence 95% CI References ND to EAC 57 studies 3.3/10003/1000 PY 28-3 2.8-3.88 Desai, 2012 (N=11,434) 50 studies (N=14,109) 6.3/1000 PY 4.7-8.4 Sikkema, 2010 LGD to EAC LGD to HGD/EAC HGD to EAC 24 studies (N=2694) 4 studies (N=236) 5.4/1000 PY 3-8 Singh, 2014 173/1000 PY 100-250 Singh, 2014 7/100 PY 5-8 Rastogi, 2008 Shaheen et al, AJG 2015 Guideline, Submitted The Patient Should Remain on Daily PPI ASA or NSAIDs not routinely advised Singh 2014 (Strong recommendation, Moderate level evidence) Corley 2003 (Conditional recommendation, High level evidence) Copyright 2015 American College of Gastroenterology 5
Further Management Issues Hiatal hernia repair is not recommended to reduce risk of EAC in patients with BE (Strong recommendation, high level evidence) RFA is not recommended for NDBE given the low risk of EAC and potential risks of RFA ( Strong recommendation, very low level evidence) Surveillance recommendations Every 3-5 years 4 quadrant biopsies every 2 cm EMR for mucosal abnormalities Brush Biopsy Management of Low Grade Dysplasia 60 year-old male with history of long-segment flat BE. First EGD with NDBE GERD daily after dinner and uses TUMS up to 5-10 per day. Waking up from sleep 3/week Recent biopsies demonstrating low-grade dysplasia from distal 2 cm of the BE segment. No nodules present. NDBE Copyright 2015 American College of Gastroenterology 6
Cancer Lauren B. Gerson, MD, MSc, FACG Dysplasia Interpretation Poorly reproducible (6/6 studies) Low-grade Indefinite High-grade Negative.40 to.60 moderate agreement;.60 to.80 substantial agreement; >.80 nearly perfect agreement Montgomery et al, Hum Pathol 2001; 32:379 Limitations of Random Biopsies The distribution of goblet cells is patchy within the columnar lined distal esophagus. The yield of intestinal metaplasia on biopsies obtained from the columnar lined esophagus will depend on the length of columnar mucosa as well as the number of biopsies obtained. Dr. Prateek Sharma, Barrett s Esophagus and Esophageal Adenocarcinoma, 2001 Copyright 2015 American College of Gastroenterology 7
1 Lauren B. Gerson, MD, MSc 1 Increased DY IM (%) Overall Screening Surveillance Pubication Type No. Pts Increased DY IM% 95% CI I 2 p value 1 article 5 abstract 1548 42% 21-82% 98% 0.0 1 article 1 abstract 893 68% 52-88% 95% 0.0 1 article 1 abstract 570 19% 13-27% 0% 0.6 Post-Ablation 3 abstracts 85 83% 37-184% 69% 0.04 Increased DY Publication Increased DY Dysplasia (%) Types No. Pts Dysplasia 95% CI I 2 p value Overall Surveillance 2 articles 2 abstract 761 30% 16-55% 95% 0.0 2 articles 1 abstract 721 36% 15-64% 97% 0.0 Post-Ablation 1 abstract 40 20% 5-155% 27% 0.24 Table 2. Results of the Meta-Analysis CumulativeprogresionratetoHGD/Ca 1.0 0.8 0.6 0.4 0.2 0.0 LGD Al patients NDBE ID 0 20 40 60 80 10 120 Folow-upinmonths Figure 2. Kaplan Meier curve with cumulative risk of developing high-grade dysplasia (HGD) or carcinoma (Ca) for the whole inception cohort and patients with a consensus diagnosis of low-grade dysplasia (LGD), indefinite for dysplasia (ID), or non-dysplastic Barrett s esophagus (NDBE). Curvers, AJG 2010 Copyright 2015 American College of Gastroenterology 8
Management of LGD Review by 2 pathologists (at least one with GI expertise) should occur in the setting of dysplasia (Strong recommendation, moderate level l evidence) ) Anti-secretory therapy with PPI Repeat endoscopy in 12 month s time Options for confirmed LGD: Endoscopic surveillance Radiofrequency ablation 24 studies, 2694 pts Mean F/U > 2 years Rate to EAC = 0.54% Rate to HGD/EAC = 1.7% Heterogeneity y( (I 2 =63%) Singh, GIE 2014 Copyright 2015 American College of Gastroenterology 9
* Or Yearly Surveilllance Shaheen et al. AJG Guideline 2015, Submitted Shaheen et al. AJG Guideline 2015, Submitted Copyright 2015 American College of Gastroenterology 10
Should You Perform Endoscopic Ultrasound? Routine staging in nodular BE with EUS has no benefit and should not occur prior to EMR (Strong recommendation, moderate level evidence) In patients with T1b disease, EUS may have a role in assessment of regional LN (Strong recommendation, moderate level evidence) Post-Endoscopic Therapy, Now What? Recurrence rates 20-30%; 25% dysplastic Definition varies depending upon whether GEJ/cardia is included Endoscopic surveillance is recommended (Low level evidence) If HGD/IMC, recommend every 3 months for the first year, then q6 months and then every year (Low level evidence) White light imaging/nbi incuding retroflexed views (Low level evidence) Control of symptoms with PPI (Very low level evidence) Gupta, Gastroenterology 2013 Copyright 2015 American College of Gastroenterology 11
Take Home Points Screen the Right Patients Define Your Landmarks Correctly! Do A Good Job with Your Biopsy Protocol and consider brushing Offer Surveillance to Appropriate Candidates Refer to Tertiary Center for EMR and/or RFA Work with an Experienced GI Pathologist Continue Surveillance Post-RFA Thank You for Your Attention Copyright 2015 American College of Gastroenterology 12