Barrett s Esophagus. Abdul Sami Khan, M.D. Gastroenterologist Aurora Healthcare Burlington, Elkhorn, Lake Geneva, WI

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1 Barrett s Esophagus Abdul Sami Khan, M.D. Gastroenterologist Aurora Healthcare Burlington, Elkhorn, Lake Geneva, WI A 58 year-old, obese white man has had heartburn for more than 20 years. He read a magazine article saying that heartburn is a risk factor for Barrett s esophagus, which can lead to cancer of the esophagus. The article went on to say that people with heartburn should have an endoscopy to look for Barrett s esophagus. The article scared him, and he asks you what he should do. Endoscopy reveals Barrett s esophagus. Biopsy specimens show high-grade dysplasia.

2 Me Co tapl Ep lum asti ith na c eli r um Metaplastic Columnar Epithelium Barrett s Esophagus Stratified Squamous Epithelium The condition in which a metaplastic columnar epithelium that predisposes to cancer development replaces the stratified squamous epithelium that normally lines the distal esophagus Affects 5.6% of adult Americans AGA Medical Position Statement. Gastroenterology 2011;140:1084. Barrett s Metaplasia Esophageal Adenocarcinoma Metaplasia One adult cell type replaces another type Response to Chronic Tissue Injury GERD Reflux Esophagitis Stratified Squamous Epithelium (Normal Esophagus) Specialized Intestinal Metaplasia (Barrett s Esophagus)

3 GEJ (Gastro-Esophageal Junction) Z-Line (Squamo-Columnar Junction) X Columnar Lined Esophagus Specialized Intestinal Metaplasia Adapted from Spechler. Gastroenterology 1999;117:218. Risk Factors for Barrett s Esophagus and Esophageal Adenocarcinoma Chronic GERD Heartburn, hiatal hernia Age >50 years Uncommon in children Male gender White ethnicity Less common in African-Americans Uncommon in Asians Obesity Intra-abdominal fat distribution Guidelines for Endoscopy in GERD Upper endoscopy is indicated in men and women with heartburn and alarm symptoms (dysphagia, bleeding, anemia, weight loss, and recurrent vomiting). Upper endoscopy is indicated in men and women with typical GERD symptoms that persist despite a therapeutic trial of 4 to 8 weeks of twice-daily proton pump inhibitor therapy. ACP Guidelines. Shaheen. Ann Intern Med 2012;157:808. Upper endoscopy is not required in the presence of typical GERD symptoms. Endoscopy is recommended in the presence of alarm symptoms and for screening of patients at high risk for complications [Barrett s esophagus]. ACG Guidelines. Katz. Am J Gastroenterol 2013;108:308.

4 AGA Medical Position Statement on Endoscopic Screening for Barrett s Esophagus We recommend against screening the general population with GERD for Barrett s esophagus. In patients with multiple risk factors associated with esophageal adenocarcinoma, we suggest screening for Barrett s esophagus. Chronic GERD, hiatal hernia, age 50, male gender, white race, elevated BMI, intra-abdominal body fat distribution Gastroenterology 2011;140:1084. Norman Barrett Incidence per 1,000,000 U.S. Incidence of Esophageal Adenocarcinoma Has Been Rising Incidence Time Trend 15 7-Fold Increase In 3 Decades per million per million Pohl H. Cancer Epidemiol Biomarkers Prev 2010;19:1468. Estimates of Cancer Risk for Individual Patients with Non-Dysplastic Barrett s Have Been Getting Lower 1990s Estimate: 1% per year 1 in 100 patients per year Drewitz. Am J Gastroenterol 1997;92: s Estimate: 0.5% per year 1 in 200 patients per year Shaheen. Gastroenterology 2000;119: Estimate: 0.25% per year 1 in 400 patients per year

5 Endoscopic Surveillance Might Not Decrease Mortality from Esophageal Adenocarcinoma 8,272 pts. with Barrett s esophagus (BE) Surveillance endoscopy withinadenocarcinoma 3 years was NOT associated 351 pts. with esophageal (EAC) with decreased risk of death from esophageal cancer 70 EAC in pts. with prior diagnosis of BE ( 6 months) (adjusted odds ratio 0.99; 95% CI ) Cases Controls 38 pts. with confirmed death 101 living Barrett s pts. matched from esophageal cancer for age, sex, follow-up duration 55% 60% surveillance endoscopy performed within 3 years surveillance endoscopy performed within 3 years Corley DA. Gastroenterology 2013;145:312. Do Proton Pump Inhibitors (PPIs) Prevent Cancer in Barrett s Esophagus? PPIs are the most effective medical treatment for reflux esophagitis Decrease gastric acid production Decrease acid reflux Heal reflux esophagitis Evidence that PPIs prevent carcinogenesis in Barrett s esophagus is indirect and not proven in controlled trials. PPIs Reduce the Risk of Neoplastic Progression in Barrett s Esophagus 540 Barrett s patients, median follow-up 5.2 years PPI Nonusers PPI use associated with 75% reduction in risk of neoplastic progression PPI Users Kastelein F. Clin Gastroenterol Hepatol 2013;11:

6 AGA Medical Position Statement on the Treatment of GERD in Barrett s Esophagus GERD therapy with medication effective to treat GERD symptoms and to heal reflux esophagitis is clearly indicated. Antireflux surgery is not more effective than medical therapy for prevention of cancer in Barrett s esophagus. Norman Barrett Age 13 We recommend against attempts to eliminate esophageal acid exposure (PPIs in doses >once daily or antireflux surgery) for cancer prevention. Gastroenterology 2011;140:1084. AGA Medical Position Statement on Endoscopic Surveillance for Barrett s Esophagus We suggest that endoscopic surveillance [with biopsy] be performed in patients with Barrett s esophagus. We suggest the following surveillance intervals: Norman Barrett No dysplasia: 3-5 years Low-grade dysplasia: 6-12 months High-grade dysplasia in the absence of eradication therapy: 3 months Gastroenterology 2011;140:1084. The Cancer Risk for High-Grade Dysplasia in Barrett s is Sufficient to Warrant Intervention ~6% per year High Grade Dysplasia Cancer Rastogi. Gastrointest Endosc 2008;67:394. Spechler. Am J Gastroenterol 2005;100:927. AGA Medical Position Statement. Gastroenterology 2011;140:1084.

7 Management Options for High-Grade Dysplasia in Barrett s Esophagus Intensive endoscopic surveillance (every 3 months) Endoscopic ablation Endoscopic mucosal resection Esophagectomy AGA Medical Position Statement on the Management of Barrett s Esophagus We recommend endoscopic eradication therapy rather than surveillance for treatment of patients with confirmed high-grade dysplasia in Barrett s esophagus. Norman Barrett Gastroenterology 2011;140:1084. HGD Muscularis mucosae T1 Mucosa Submucosa T2 Epithelium Lamina propria Basement membrane Drawing courtesy of Tom Rice

8 T Staging of Esophageal Cancer Muscularis mucosae Mucosa T1 Submu cosa Mucosa Submucosa ris Muscula propria T4 T2 T3 None considered curable by endoscopic therapy. Drawing courtesy of Tom Rice HGD T1 T2 High Grade Dysplasia Muscularis mucosae Mucosa Submucosa Intramucosal Carcinoma T1a T1b T1b: LN mets >10% Potentially curable with endoscopic therapy Potentially metastatic Drawing courtesy of Tom Rice Systematic Review: Risk of Lymph Node Metastases for High Grade Dysplasia (HGD) or Intramucosal Carcinoma (IMC) in Barrett s Esophagus Reviewed studies that included: - Patients who had esophagectomy for HGD or IMC and - Final surgical pathology results (lymph node status) Identified 70 relevant articles 1,874 patients who had esophagectomy for HGD (524 patients) or IMC (1,350 patients) Lymph node metastases in 26 of 1,874 patients (1.39%, 95% CI.86% %) Dunbar K, Spechler S. Am J Gastroenterol 2012;107:850.

9 Accurate T Staging Crucial to Determine if Curative Endoscopic Therapy Feasible High Grade Dysplasia and Intramucosal Carcinoma Lymph node metastases in 1%-2% Curative endoscopic therapy feasible Submucosal invasion Lymph node metastases in >10% Failure rate for endoscopic therapy unacceptable Endoscopic mucosal resection (EMR) the best procedure for T staging EMR is as much a staging procedure as it is a therapeutic procedure. If EMR shows submucosal invasion, then endoscopic therapy is not advised. Radiofrequency Ablation (RFA) Radiofrequency Energy Generator Closely spaced electrodes

10 Radiofrequency Ablation of Barrett s Esophagus Ablated Barrett s Metaplasia Randomized, Sham-Controlled Trial of Radio-frequency Ablation for Dysplasia in Barrett s Shaheen. N Engl J Med 2009;360: % with Progression Radiofrequency Ablation of Dysplasia Prevents Neoplastic Progression at One Year 16.3% Radiofrequency ablation Sham ablation 9.3% 3.6% 1.2% Progression of Neoplasia Progression to Cancer Shaheen. N Engl J Med 2009;360:

11 Complications of Radiofrequency Ablation in 84 Patients 5 esophageal strictures (6%) 1 UGI Bleed (1%) 2 hospitalizations for chest pain (2%) Shaheen. N Engl J Med 2009;360: Endoscopic Therapy for Mucosal Neoplasia In Barrett s Esophagus 2014 EMR of mucosal irregularities for staging and therapy Ablate the remaining Barrett s metaplasia to minimize metachronous neoplasia PROPOSAL: Routine Polypectomy for Colon Polyps and RFA for Non-Dysplastic Barrett s Esophagus Are Intellectually the Same Non-dysplastic Barrett s esophagus is like a small colon polyp = RFA, like colonoscopy, is safe and effective Limiting RFA only to Barrett s with dysplasia is like limiting polypectomy only to polyps that are large or clearly malignant. El-Serag HB, Graham DY. Gastroenterology 2011;140:386.

12 U.K. Experience with EMR and RFA for Treatment of Mucosal Neoplasia in Barrett s Esophagus 335 pts with HGD (72%), IMC (24%) or LGD (4%) One year protocol Mean 2.5 RFA % free of disease treatmentsof dysplasia 270 (81%) complete eradication 208 (62%) complete eradication of Barrett s metaplasia 10 (3%) progressed to invasive cancer 30 (9%) strictures requiring dilation, perforation Dysplasia 75 Barrett s Metaplasia Months from end of protocol 48 Haidry. Gastroenterology : RFA for Non-Dysplastic Barrett s Esophagus? Generally requires several endoscopies for complete eradication Complication rate low, but not trivial Substantial rate of recurrence of metaplasia Frequency and importance of subsquamous intestinal metaplasia not clear Efficacy in preventing cancer not established Does not obviate surveillance Chronic GERD symptoms and 1 risk factor(s) for adenocarcinoma (Age>50, male, white, hiatal hernia, obesity, intra-abdominal body fat, smoking) No No more screening onbarrett s screening Consider screening endoscopy Barrett s esophagus No dysplasia Low-grade dysplasia Surveillance endoscopy every 3-5 yrs Have diagnosis confirmed by expert pathologist Low-grade dysplasia Surveillance endoscopy every 6-12 months or endoscopic eradication High-grade dysplasia or intramucosal Ca High-grade dysplasia or intramucosal Ca Endoscopic eradication

13 AGA Medical Position Statement on the Management of Barrett s Esophagus Endoscopic eradication therapy is not suggested for the general population of patients with Barrett s esophagus in the absence of dysplasia. RFA should be a therapeutic option for select individuals with non-dysplastic Barrett s esophagus who are judged to be at increased risk for progression to HGD or cancer. Norman Barrett Thank You