Present Day Management of Barrett s Esophagus

Transcription

1 Slide 1 Present Day Management of Barrett s Esophagus Kinnari R. Kher, M.D. Slide 2 Goals Risk factors for development of Barrett s esophagus Risks for progression to Esophageal Adenocarcinoma Current Treatment of Barrett s esophagus No financial disclosures Slide 3 Definition Change in the lining (Metaplasia) of the esophagus from squamous to columnar epithelium Intestinal metaplasia = Goblet cells Protection from acid, but premalignant potential

2 Slide 4 History Pioneering thoracic surgeon ( ) Postulated Congenitally shortened esophagus; later accepted the concept of a sliding hiatal hernia Also initially supported a developmental etiology for metaplastic columnar-lined esophagus Mr. Norman Barrett Slide 5 Endoscopic Appearance library.med.utah.edu Image courtesy Academic Medical Center, Netherlands Slide 6 From Metaplasia to Dysplasia to Carcinoma Ong, World J Gastroenterol, 2010

3 Slide 7 Barrett s Esophagus Esophageal AdenoCarcinoma Images courtesy Academic Medical Center, The Netherlands Slide 8 Chronic GERD causes Barrett s 1 in 5 have weekly GERD symptoms 2 in 5 have monthly symptoms Heartburn, Acid regurgitation Atypical GERD (cough, asthma, laryngitis, chest pain) Slide 9 Evolution of Barrett s Injury: Acid and bile reflux Genetics: Gender, race, other factors Accumulate genetic changes Diagram courtesy Covidien, Inc.

4 Slide 10 Barrett s Esophagus and Esophageal Adenocarcinoma Barrett s esophagus is the primary risk factor for the development of esophageal adenocarcinoma fold increased risk even without dysplasia Pohl, J Natl Cancer Inst, 2005 de Jonge, Gut, 2010 Hvid-Jensen, N Engl J Med, 2011 Surveillance, Epidemiology and End Results (SEER) (accessed Sept 23, 2013) Slide 11 Esophageal Adenocarcinoma Is One of the Fastest Growing Cancers of the Past Four Decades Esophagus Melanoma Prostate Lung/Breast Colorectal Pohl, J Natl Cancer Inst, 2005 Slide 12 Age-adjusted 5-year survival

5 Slide 13 Protocol to date: Surveillance biopsies every 2 cm x 4 quadrants Surveillance Is Hampered by Sampling Error Does not reduce deaths from Esophageal cancer Falk, Tech Gastrointest Endosc, 2000 Sharma, Clin Gastroenterol Hepatol, 2006 Slide Year Cancer Risk of ~ 3% for all cases Bhat, J Natl Cancer Inst, 2011 Slide 15 Well-Studied & Commonly Accepted Clinical Factors May Further Elevate This Progression Risk Caucasian Male Smoker Obese

6 Slide 16 Well-Studied & Commonly Accepted Clinical Factors May Further Elevate This Progression Risk Caucasian Male Smoker Obese bullandbearnaperville.com Slide 17 Additional Risk Factors Young Age Large Hiatal Hernia Family History of Barrett s Esophagus and Esophageal Adenocarcinoma Long Segment Barrett s Esophagus nothingiswrittenfilm.blogspot.com thoracic.surgery.virginia.edu Slide 18 Long Segment Non Dysplastic Barrett s Progresses to High Grade Dysplasia/Carcinoma at a Significantly Elevated Rate Short Segment Long Segment 28% increase in risk of progression per 1 cm increase in length (p<0.001) Anaparthy, Clin Gastroenterol Hepatol, 2013

7 Slide 19 Dysplasia carries a Substantial Annual Cancer Progression Risk Low Grade Dysplasia confirmed by two pathologists 3.4% annual progression risk' High Grade Dysplasia 10% annual progression risk² 'Curvers, Am J Gastroenterol, 2010 ²Bennett, Gastroenterology, 2012 Slide 20 What modalities of treatment have we been using? Slide 21 Surgical Therapy Esophagectomy Argon Plasma Coagulation Cryoablation PhotoDynamic Therapy Endoscopic Mucosal Resection Endoscopic Therapies APC PDT Cryo EM R Images courtesy Covidien.com

8 Slide 22 Human Esophagus Epithelium Lamina Propria Muscularis Mucosae Submucosa Muscularis Propria G G Radiofrequency Ablation Photodynamic therapy/argon Plasma Coagulation/ Cryotherapy Endoscopic Mucosal Resection Grade AJ, Gastrointest Endosc, 1999 Overholt BF, Gastrointest Endosc, 2007 Fleischer DE, Endoscopy, 2010 Shaheen NJ, Gastrointest Endosc, 2010 Smith CD, Surgical Endosco, 2007 Shaheen NJ, N Engl J Med, 2009 Sharma P, Gut, 2006 Surgical Depth Slide 23 Barrx TM Flex Generator Circumferential Ablation: Focal Ablation: BarrxTM 360 BarrxTM Ultra Long BarrxTM 90 BarrxTM 60 BarrxTM Channel US USA, September 2013 Slide 24 Circumferential Ablation Images courtesy Covidien, Inc.

9 Slide 25 Pre- & Immediately post- Circumferential Ablation Images courtesy Academic Medical Center, The Netherlands Slide 26 2 years post-circumferential Ablation Images courtesy Academic Medical Center, The Netherlands Slide 27 Focal Ablation Images courtesy Covidien, Inc.

10 Slide 28 Appearance pre- and immediately post- Focal Ablation Images courtesy Charles Lightdale, M.D., New York-Presbyterian Hospital Slide 29 Endoscopic Mucosal Resection (EMR) of Esophageal nodules and Intramucosal carcinoma (IMC) Slide 30 Pre-procedure Instructions Set Realistic Expectations: Chest pain/dysphagia in <25% of patients for upto 4 days Average 3 sessions, 9-12 weeks apart Fill Rx and bring to procedure Administer first dose of pain med in the recovery room 2 months for neosquamous epithelium to grow following RFA & EMR Good follow up is critical for a cure

11 Slide 31 Post-procedure Instructions Diet Liquid x 2 days (avoid hot liquids) and soft x 1 week Activities No physical restrictions What to take High dose PPIs (1 week before & 1 month after RFA) Esomeprazole (Nexium) 40mg PO bid What to Avoid Anti-coagulants (1 wk before & after RFA) Anti-platelet agents Aspirin, NSAIDS, Plavix Anti-thrombotic agents - Coumadin Slide 32 Drugs GI cocktail (1:1 ratio) - 15ml PO q4hr PRN Maalox 2% viscous Lidocaine Sucralfate (Carafate) 1gm PO q6hr PRN min before meals and at bedtime Acetominophen (Tylenol) w/ codeine elixir (15mg/5ml) 15ml PO q4hr PRN Slide 33 When to call/come in Fever Significant chest or abdominal pain Tachycardia Dysphagia Bleeding (hematemesis or melena)

12 Slide 34 Adverse Events (143,264 procedures) Death (procedure related): 0% Stricture: 1.7 in 1,000 Bleeding: 2 in 1,000 procedures Perforation: 1 in 11,938 procedures (.08 in 1,000) Mucosal injury: 1 in 1,000 Slide 35 RFA procedure Slide 36 Contraindications to RFA Esophageal varices Eosinophilic Esophagitis Need for ongoing anticoagulation Prior radiation therapy to mediastinum Pregnancy

13 Slide 37 Slide 38 Complete eradication (Intention-to-Treat) Shaheen NJ, et al. N Engl J Med 2009 Slide 39 Study Conclusion In this multi-center, randomized, shamcontrolled study of RFA in patients with dysplastic Barrett s, there was a: high rate of complete eradication of dysplasia and intestinal metaplasia, and decreased disease progression in the ablation group, as compared with the control group Shaheen NJ, et al. N Engl J Med 2009

14 Slide 40 Other studies support this data For dysplastic Barrett s, RFA reduces progression of the dysplastic sequence Durable for 3 years For nondysplastic Barrett s, if treatment is undertaken, RFA is durable for 5 years Shaheen, N Engl J Med, 2009 Fleischer, Endoscopy, 2010 Phoa, Gastroenterology, 2013 Slide 41 RFA Can Eliminate Genetic Abnormalities Baseline Genetic Abnormalities Pt IHC Ki- IHC p53 CEP 1 CEP 9 p16 p Gain N Loss Loss Post-RFA Genetic Findings N N Loss Loss Gain Gain Loss N Gain N Loss N N N N Loss Gain N N Loss Negative Gain N N N Gain Gain Loss Loss N N N Loss N N N Loss Pouw RE, et al. Am J Gastroenterol 2009 Slide 42 RFA Treats Buried Glands Older treatment options left columnar epithelium in deeper layers of the mucosa Multiple studies have showed 0 to 0.9% rate of buried columnar glands after RFA Image from Yuan, Endoscopy, 2012

15 Slide 43 GI Societal Recommendations ACG AGA ASGE SAGES Panel of Experts RFA is superior to surveillance in High Grade Dysplasia RFA + EMR is the treatment of choice in Intramucosal Carcinoma or Dysplasia with esophageal nodules Slide 44 GI Societal Recommendations ACG AGA ASGE SAGES Panel of Experts For confirmed Low Grade Dysplasia, RFA versus surveillance should be discussed with the patient For Intestinal Metaplasia, RFA should be a therapeutic option for those at increased risk for progression Slide 45 RFA with Nissen Fundoplication SAGES GERD Guidelines Anti-reflux surgery may be performed before, during or after ablative therapy SAGES Guidelines Committee, 2010

16 Slide 46 The US RFA Registry Consists of 5,530 Patients Enrolled at 148 Sites from IMC, 200, 3.7% HGD, 1018, 18.8% Invasive cancer, 59, unknown, 1.1% 29, 0.5% Non- Dysplastic, 2617, 48.3% LGD, 1089, 20.1% Indefinite, 404, 7.5% Pasricha, Gastroenterology, 2013 Slide 47 Conclusions Those with chronic acid reflux must be screened for Barrett s Esophagus Surveillance of Barrett s esophagus does not reduce deaths from esophageal cancer Dysplasia carries a substantial annual cancer progression risk RFA safely reduces progression to HGD and EAC in dysplastic patients