Slide 1 DIAGNOSIS AND TREATMENT 1 Slide 2 DISCLOSURES Successful completion: Participants must attend the entire program, including any resulting Q & A, and submit required documentation. Conflict of interest: This presentation is supported by Covidien-GI Solutions. Planners disclose no conflict of interest; the speaker discloses a relationship with the supporting company. Commercial company support: Fees are underwritten by education funding and commercial support provided by Covidien-GI Solutions. Non-commercial company support: None. Non-endorsement of products: Educational Dimensions, the Accredited Provider, is philosophically dedicated to the provision of quality CNE and does not endorse products or services provided by the commercial support entity. Off-label product use: None. Alternative or Complementary Therapy: None. 2 Slide 3 EXPECTED OUTCOMES The Nurses will have increased knowledge on the disease state and treatment options for Barrett s esophagus, thus being better prepared for patient education and teaching Nurses will be better informed regarding the latest techniques for endoscopic eradication therapies 3
Slide 4 OBJECTIVES Describe the precursors and disease process for Barrett's esophagus Detail the various approaches to managing Barrett s esophagus 4 Slide 5 BARRETT S ESOPHAGUS INTESTINAL METAPLASIA Image source of Professor N. Barrett internet search public domain. First described by Professor Norman Barrett in 1950 as a tubular portion of stomach being trapped in the chest Related to the esophagus in 1953 (Allison/Johnstone) Metaplasia = change in cell-type Prof. Norman Barrett Intestinal Metaplasia is when the esophageal squamous cells change to specialized intestinal cells Barrett NR (October 1950). "Chronic peptic ulcer of the oesophagus and 'esophagitis'". Br J Surg 38 (150): 175 82 Allison PR, Johnstone AS (June 1953). The oesophagus lined with gastric mucous membrane. Thorax 8 (2): 87 101. Barrett NR (June 1957). "The lower esophagus lined by columnar epithelium". Surgery 41 (6): 881 94. Spechler SJ, Goyal RK (February 1996). "The columnar-lined esophagus, intestinal metaplasia, and Norman Barrett". Gastroenterology 110 (2): 614 21 5 Slide 6 WHAT IS BARRETT S ESOPHAGUS? Image: http://www.gastroenterologistpaloalto.com/images/radiofrequency ablation1.jpg Image: http://www.gastrohep.net/freespeech/case250405-fig03.jpg 6
Slide 7 WHAT IS GASTROESOPHAGEAL REFLUX DISEASE GERD? Chronic heartburn (GERD symptom) is a physical condition Inability of the lower esophageal sphincter (LES) to prevent reflux of acid from the stomach into the esophagus Causative factor of Barrett s Esophagus Image: http://blog.itechtalk.com/wp-content/2009/12/gerd.jpg 7 Slide 8 CAUSE OF INTESTINAL METAPLASIA BARRETT S ESOPHAGUS A response to chronic exposure of gastric acid Cells of the Esophageal lining undergoes changes in organization Results in formation of Intestinal Metaplasia (Barrett s esophagus) http://digestiveonline.com/images/content/gerd.gif 8 Slide 9 ESOPHAGEAL HISTOLOGY Esophageal Epithelium ~500µm Lamina Propria Muscularis Mucosae ~1000µm Submucosa Muscularis Propria Image: http://www.barrx.com/images/uploads/humanesophagus-specimen.jpg 9
Slide 10 STAGES OF BARRETT S ESOPHAGUS Non Dysplastic Intestinal Metaplasia (NDIM) Indefinite Low-Grade Dysplasia High-Grade Dysplasia Which can lead to Intramucosal Carcinoma (Adenocarcinoma) 10 Slide 11 CAN YOU TELL WHAT STAGE THESE HISTOLOGY SLIDES SHOW? Inter-observer agreement is moderate at best, and in some studies it is poor Non-dysplastic It s called discordance For the diagnosis for Barrett s with dysplasia, it is recommended that two pathologist should agree or bring in a third to concur Low-grade dysplasia High-grade dysplasia Adenocarcinoma Fleischer DE, Odze R, et al. The Case for Endoscopic Treatment of Non-dysplastic nd Low-Grade Dysplastic Barrett s Esophagus, Dig Dis Sci DOI 10.1007/s10620-010-1218-1. 11 Image from: Huang Q, et al. BMC Clin Pathol. 2005 Aug 12;5:7 Slide 12 GRADING OF BARRETT S ESOPHAGUS AND ASSOCIATED RISK LEVEL Esophageal Adenocarcinoma 1.4 % per patient per year (IM to HGD and EAC) High Grade Dysplasia 6.6% per patient per year (HGD to EAC) Low Grade Dysplasia 1.7% per patient per year (LGD to EAC) 4.0% per patient per year (IM to LGD) Non- Dysplastic 0.5% per patient per year (IM to EAC) 0.9% per patient per year (IM to HGD )
Slide 13 EVOLUTION OF BARRETT S AND CANCER Squamous esophagus Chronic inflammation Barrett's metaplasia Low-grade dysplasia Injury Acid & bile reflux nitrous oxide Genetics Gender, race, & other factors (cox-2) High-grade dysplasia Invasive Adenocarcinoma Accumulate Genetic Changes Morales CP et al. Lancet 2002; 360: 1587-89 13 Slide 14 DID YOU KNOW THAT BARRETT S AND A COLON POLYP HAVE SOMETHING IN COMMON? Barrett s 0.5%/patient/year cancer 0.9%/patient/year HGD Colon Polyp 0.5%/patient/year cancer 7.5M colonoscopies/year Sharma P, Falk GW, Weston AP, Reker D, Johnston M, Sampliner RE. Dysplasia and Cancer in a Large Multicenter Cohort of Patients with Barrett s Esophagus. Clinical Gastroenterology and Hepatology 2006;4:566-572 14 Slide 15 RELATIVE CHANGE IN ESOPHAGEAL ADENOCARCINOMA INCIDENCE Esophagus Melanoma Prostate Lung/Breast Colorectal From: Pohl H, Welch HG. Natl Cancer Inst 2005 15
Slide 16 DEMOGRAPHICS OF BARRETT S ESOPHAGUS About 13% of Caucasian men over age 50 who have chronic reflux GERD will develop Barrett's esophagus A study by the Veteran Affairs Healthcare System and Stanford University found that 25% of patients over 50 without GERD symptoms had Barrett's esophagus Westhoff B, Brotze S, Weston A, et al. The frequency of Barrett s esophagus in high-risk patients with chronic gerd. Gastrointestinal Endosc. 2005; 61:226-231. Gerson LB, Shetler K, and Triadafilopoulos G. Prevalence of Barrett s esophagus in asymptomatic individuals. Gastroenterology 2002;123:461-467 16 Slide 17 BARRETT S PREVALENCE ESTIMATES 1.6% of general adult population (3.3 M) Ronkainen J, et al. Prevalence of BE Gastroenterology 2005;129:1825-31. 3.9% 5.6% of general adult population (7.8-11.2 M) Tristan J, et al. The Prevalence of BE in the US (model)...ddw 2009. Hayeck TJ, et al. The Prevalence of BE in the US (model) Dis Esophagus 2010;23:451-7. 6.8% of persons over age 40 (8.7 M) Rex DK, et al. Screening for Barrett s... Gastroenterology 2003; 125:1670-77. 17 Slide 18 THREE MANAGEMENT STRATEGIES FOR BARRETT S ESOPHAGUS 1. Surveillance and Medical Management 2. Surgery and or Endoscopic Mucosal Resection 3. Ablation: Destroy the abnormal cells to allow normal squamous cells to re-populate. A. Chemical Photodynamic Therapy APC B. Freezing Cryotherapy C. Thermal Circumferential and Focal RFA December 31, 2009 Strategies and recommendations for diagnosing and managing Barrett's esophagus are presented in a review published in the December 24 issue of the New England Journal of Medicine. 18
Slide 19 SURVEILLANCE Technique: AGA recommends the Seattle protocol Four quadrants every 1cm - 2 cm through the Intestinal Metaplasia visible areas Intervals: Based on pathology of :dysplasia 3-6-12 months or non-dysplasia 3-5 years Goal: The early detection of dysplasia and early cancer Limitations: Does not remove Barrett s, and increases patient anxiety Samples only 4-6% of esophagus Sampling errors and pathology discordance Surveillance intervals are arbitrary and have never been subject to a clinical trial. Endoscopic Surveillance, 2005 ClevelandClinic.org, The Cleveland Clinic, 9 August 2005 <http://cms.clevelandclinic.org/digestivedisease/body.cfm?id=240>. 19 Slide 20 HUMAN ESOPHAGUS Esophageal mucosa Biopsy depth Submucosa with esophageal G glands G Muscularis mucosa Muscularis propria. Image: http://www.barrx.com/images/uploads/humanesophagus-specimen.jpg Prateek Sharma, M.D.. N Engl J Med 361;26 NEJM.org December 24, 2009 20 Slide 21 Reserved for patients with high grade dysplasia and cancer Definitive therapy Operative mortality rate of 3-12% Rate of serious operative complications of 30-50%. 21
Slide 22 ENDOSCOPIC MUCOSAL RESECTION (EMR) Indications Focal, raised lesion(s) Larger areas suspicious for malignancy Complement to other therapies Goal: Remove lesion(s) so the tissue can be examined under a microscope to determine if all of the cancer (or dysplasia) has been removed. Images:http://www.hopkins-gi.org/Upload/200809021614_28380_000.jpg 22 Slide 23 ENDOSCOPIC MUCOSAL RESECTION (EMR) Several Techniques One Technique: The focal EMR is done using a small cap that has a small wire loop that fits on the end of the endoscope. The nodule is suctioned into the cap and the wire loop is closed while cautery is applied. Step 1: Injection of Target Lesion Step 2: Positioning the Snare Step 3: Suction and Snare of Lesion Images:http://www.hopkins-gi.org/Upload/200809021614_28380_000.jpg Second Technique: The focal EMR is done using a small ligation band, followed by a cautery loop The cautery loop is around the nodule and energy applied. Once the nodule is released from the mucosal wall, it is retrieved in the usual fashion. Images; http://www.cookmedical.com/esc/datasheetfeature.do?id=4439 23 Slide 24 ENDOSCOPIC MUCOSAL RESECTION (EMR) Advantages: Enables evaluation of changes in diseased tissue Can be used to obtain large biopsies for diagnosis and local tumor staging Frequently reveals more advanced tumor stages Often recommended in combination with additional ablation techniques Limitations and possible complications Creates a scarring effect If done circumferentially EMR has up to an 88% chance of causing a stricture Images: http://www.atillaertan.com/images/photo-sl-endoscopic-2.jpg 24
Slide 25 HUMAN ESOPHAGUS Esophageal Mucosa Image: http://www.barrx.com/images/uploads/humanesophagus-specimen.jpg Submucosa with esophageal G glands G Muscularis mucosa EMR Depth Esophagectomy CR-D : 100% CR-IM : 92% Radical EMR Strictures: 88% # Therapeutic Sessions: 6 Muscularis propria Operative mortality rate of 3-23% Rate of serious operative complications of 30-50%. Surgical Depth van Vilsteren FG, et al. Stepwise radical endoscopic resection versus radiofrequency ablation for Barrett s oesophagus with high-grade dysplasia or early cancer: a multicentre randomized trial. Gut, epub January 2011. 25 Slide 26 ARGON PLASMA COAGULATION Indications Focal area of Barrett s (NDIM) Goal: Remove the Barrett s lesion Technique: Utilizes an argon gas device that employs chemical energy Through a hand-held device, it creates an electrical arc on the tissue to a specific focal area Advantages: Hand held Small focal areas Pereira-Lima JC, Am J Gastroenterol 2000; 95:1661-8 Kahaleh M, Endoscopy 2002; 34:950-5. Image:http://www.bing.com/images/search?q=endoscopic+musc oal+resection++photos&qpvt=endoscopic Limitations and possible complications Technically demanding Non-uniform ablation effect User variability Buried glands Anatomy of distal esophagus not considered, its not round 26 Slide 27 HUMAN ESOPHAGUS Esophageal mucosa Image: http://www.barrx.com/images/uploads/humanesophagus-specimen.jpg APC Submucosa with esophageal G glands G Muscularis mucosa) Varied results CR-IM: 42%-98% Strictures: 2.9%-10% Persistent Buried Barrett's (SSIM): 8%- 30% Deviere J. Argon plasma coagulation therapy for ablation of Barrett s oesophagus Gut. 2002 December; 51(6): 763 764. Muscularis propria Multiple cases of adenocarcinoma arising under the squamous reepithelialization have been observed after APC. Menon et al. Endoscopic treatments for Barrett s esophagus: a systematic review of safety and effectiveness compared to esophagectomy BMC Gastroenterology 2010, 10:111 http://www.biomedcentral.com/1471-230x/10/111. 27
Slide 28 Indications PHOTODYNAMIC THERAPY PDT High Grade Dysplasia (HGD) Barrett's esophagus Goal: Eliminate HGD using an endoscopic therapy rather than surgical esophagectomy Technique: A. Photosensitizer drug given intravenously B. Affected esophagus exposed to non-ablative laser light for ~12 minutes B. Oxygen free radicals induced in high light dose areas C. Free radicals induce cell death Images: http://www.gaspa.com/wp-content/uploads/2009/11/photodynamic-therapy- Overholt BF, Lightdale CJ, Wang KK et al. Photodynamic therapy with porfimer sodium for ablation of high-grade dysplasia in Barrett's esophagus: international, partially blinded, randomized phase III trial. Gastrointestinal Endoscopy, 2005,62(4);488-498. 28 Slide 29 HUMAN ESOPHAGUS Esophageal mucosa Image: http://www.barrx.com/images/uploads/humanesophagus-specimen.jpg PDT Submucosa with esophageal G glands G Muscularis mucosa Meta Analysis of 101 studies CR-IM: 51.6% CR-D: 77.5% Strictures: 18.5% Buried Barrett s (SSIM): 14.2% Photosensitivity: 26.4% Muscularis propria Menon et al. Endoscopic treatments for Barrett s esophagus: a systematic review of safety and effectiveness compared to esophagectomy BMC Gastroenterology 2010, 10:111 http://www.biomedcentral.com/1471-230x/10/111. Gray NA, Odze RD, Spechler SJ., Buried metaplasia after Endoscopic Ablation n of Barrett's Esophagus: a Systematic Review. AM J Gastroenterology, 2011 Aug 9, doi 10.1038/aja 2011: 255[epub ahead of print] 29 Slide 30 Advantages: PDT Photodynamic therapy was the first treatment to have been shown to significantly decrease high-grade dysplasia and cancer in patients with Barrett s esophagus Limitations and possible complications Its use has been limited, primarily because of its costs and side effects Subsquamous Barrett's (buried glands) Strictures that are stenotic and fibrotic Photosensitivity Chest pain Nausea Vomiting Photosensitivity Stricture Subsquamous Barrett s 30 Wang KK, Nijhawan PK. Complications of photodynamic therapy in gastrointestinal disease. Gastrointest Endosc Clin N Am 2000; 10:487-95. Overholt BF, Lightdale CJ, Wang KK et al. Photodynamic therapy with porfimer sodium for ablation of high-grade dysplasia in Barrett's esophagus: international, partially blinded, randomized phase III trial. Gastrointestinal Endoscopy, 2005,62(4);488-498.
Slide 31 Indications Barrett's esophagus with high-grade dysplasia and persistent low-grade dysplasia Early stage esophageal cancer not amenable to standard therapies including surgery, chemotherapy, and radiation therapy Goal: By freezing the tissues using extreme cold, (-196 Celsius) it will remove the abnormal cells and allow re-growth of new, healthy cells in their place. Technique: CRYOTHERAPY There are currently two different types of cryotherapy available Rapid flow of CO 2 or liquid nitrogen Sprayed to the affected esophageal lining Repeat treatments necessary 3 up to 8 times reported Images: websites for CSA and GI Supply CSA Website accessed 8. 2011 31 Slide 32 HUMAN ESOPHAGUS Ablation Target Nicholas J. Shaheen, MD, MPH, et al. Safety and efficacy of endoscopic spray cryotherapy for Barrett s esophagus with high-grade dysplasia. Gastrointest Endosc. 2010 April ; 71(4): 680 685. doi:10.1016/j.gie.2010.01.018. CRYOTHERAPY One retrospective study of 98 patients reported 60 patients completed the therapy 58 patients had complete response to removing HGD=97%, BUT of those, 52 of them had showed only downgrading of histology: 87% HGD to Non-Dysplastic, not a complete removal of disease. Submucosa with esophageal G glands Muscularis propria G Muscularis mucosa) 34 patients had a completed response to Intestinal metaplasia= 57%. Did not achieve CR-IM in all patients or remove all of the Barrett s Image: http://www.barrx.com/images/uploads/humanesophagus-specimen.jpg 32 Slide 33 CRYOTHERAPY Advantages: Able to treat large, or stricture areas Coating of ice creates a whitened appearance Thru the scope device Limitations and possible complications: No visual endpoint as to when there is enough treatment User variability Gastric distention Limited support in the 2011 AGA position statement Limited data, no RCT Image: http://www.csamedical.com/treatment/endoscopic.html 33
Slide 34 RADIOFREQUENCY CIRCUMFERENTIAL AND FOCAL ABLATION Fleischer DE, Overholt BF, Sharma VK, et al. Long-term (2.5 year) follow-up of the AIM-II trial for ablation of Barrett esophagus: results after primary circumferential ablation followed by secondary focal ablation. Gastrointest Endosc 2007; 65: AB 135. Indications Barrett s esophagus Non-nodular, NDIM, LGD and HGD Goal: Delivery of ablative energy in less than 1 second allows long or short segments of Barrett s to be treated quickly Consistent application of bipolar energy uniformly removes the esophageal epithelium, reducing potential for buried glands and improving patient tolerability Controlled treatment depth of less than 1,000 μm reduces risk of stricture formation Fleischer DE, Overholt BF, Sharma VK, et al. Endoscopic Radiofrequency Ablation for Barrett s Esophagus: Five-Year Durability Outcomes from a Prospective Multi-Center Trial. Gastrointest Endosc 2010;71:AB117-118 34 Slide 35 RADIOFREQUENCY CIRCUMFERENTIAL AND FOCAL ABLATION Technique: Endoscopic evaluation of Barrett s extent Size Ablate with visual placement Clean Repeat 35 Slide 36 HUMAN ESOPHAGUS RFA resulted in complete eradication of disease in 98% of NDBE patients, with 2.5-years follow-up. At 5 years, 92% of patients maintained durable cure, and no patients demonstrated neoplastic progression. Rigorous RCT Dysplasia (per protocol) CR-IM: 83% CR-LGD: 95% CR-HGD: 90% Strictures: 1.7% procedures Published in the NEJM Durability 91 to 98% dysplasia & IM eradication rate at 2 & 3 yrs. Ablation Target Submucosa with esophageal G glands Muscularis propria Image: http://www.barrx.com/images/uploads/humanesophagus-specimen.jpg G Circumferential and Focal RFA Controlling ablation depth minimizes complications Muscularis mucosa (Ablation Target Depth) 90+ publications Fleischer DE, Overholt BF, Sharma VK, et al. Long-term (2.5 year) follow-up of the AIM-II trial for ablation of Barrett esophagus: results after primary circumferential ablation followed by secondary focal ablation. Gastrointest Endosc 2007; 65: AB 135. Fleischer DE, Overholt BF, Sharma VK, et al. Endoscopic Radiofrequency Ablation for Barrett s Esophagus: Five-Year Durability Outcomes from a Prospective Multi-Center Trial. Gastrointest Endosc 2010;71:AB117-118 Shaheen NJ, et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med. 2009 May 28;360(22):2277-88 36
Slide 37 RADIOFREQUENCY ABLATION Limitations and possible complications Therapeutic procedural time (~35 minutes for Circumferential and ~17 minutes for Focal) versus diagnostic time of EGD (~20 minutes) Multiple intubations Possible mucosal laceration, esophageal stricture and minor acute bleeding Advantages: Automated energy delivery No user variability Controlled depth of ablation extent to ~800-1000 μm 90+ clinical publications Safety and efficacy to 5 years Clinical reports of > 90% CR-IM and CR-D Fleischer DE, Overholt BF, Sharma VK, et al. Long-term (2.5 year) follow-up of the AIM-II trial for ablation of Barrett esophagus: results after primary circumferential ablation followed by secondary focal ablation. Gastrointest Endosc 2007; 65: AB 135. Post-RFA: 2-5 years Baseline Circumferential ablation 37 Slide 38 HUMAN ESOPHAGUS APC, PDT, CRYO EMR Depth Ablation Target Submucosa with esophageal G glands Muscularis propria G Circumferential and Focal RFA Controlling ablation depth minimizes complications Muscularis mucosa (Ablation Target Depth) Surgical Depth Image: http://www.barrx.com/images/uploads/humanesophagus-specimen.jpg 38 Slide 39 SOCIETY OF AMERICAN GASTROINTESTINAL AND ENDOSCOPIC SURGEONS (SAGES) GUIDELINES Guideline for surgical treatment of GERD Includes section on BE management with evidence grading HGD and IMC can be managed with RFA ± EMR for eradication of lesion and reduction in cancer (Level I evidence) Surgery remains option for HGD and IMC NDBE, IND, LGD may be effectively eradicated with RFA (Level I evidence) Anti-reflux surgery for GERD may be performed in patients with NDBE, IND, LGD in conjunction with endoscopic eradication therapy (i.e., before, during, after RFA) Source: http://www.sages.org/publication/id/22/ 39
Slide 40 THE 2011 AGA MEDICAL POSITION STATEMENT SUGGESTS RFA AS AN OPTION FOR SELECT NON DYSPLASTIC PATIENTS Surveillance Is Unproven: Endoscopic surveillance has become the standard of practice based on the unproven assumption that the practice will reduce deaths from esophageal adenocarcinoma Consider RFA for Patients with IM: we suggest that RFA, with or without EMR, should be a therapeutic option for select individuals with NDBE who are judged to be at increased risk for progression to HGD or cancer. AGA Institute Medical Position Panel, Gastro, 2011 40 Slide 41 Non-Dysplastic BE Management: Endoscopic ablation therapy may be a preferred management option in select patients with NDBE, such as those with a family history of EAC. Progression Risk Factors: Risk factors for BE and EAC include male sex, white race, age older than 50 years, family history of BE, increased duration of reflux symptoms, smoking, and obesity. 41 Slide 42 Low Grade Dysplasia Management: Ablation as an alternative to surveillance should be considered and discussed with these patients. High Grade Dysplasia Management: We recommend that eradication with endoscopic resection or RFA be considered for flat HGD 42
Slide 43 If Barrett s ablation therapy is safe and efficacious, we predict it will and possibly should become a routine response to the discovery of Barrett s esophagus, just as polypectomy is to the discovery of a colorectal polyp. (El-Serag, Graham. Gastroenterology, 2010) Barrett's esophagus Colon Polyp 43 Slide 44 CONCLUSION OF MODULE This concludes the CNE educational activity Understanding Barrett's Esophagus. Please turn in your completed evaluations. 44 Slide 45 CNE BY EDUCATIONAL DIMENSIONS Educational Dimensions is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. Provider approved by: California Board of Registered Nursing, Provider Number 08747 District of Columbia Board of Nursing, Provider Number 50-574 Florida Board of Registered Nursing, Provider Number 50-574 Iowa Board of Nursing, Provider Number 317 West Virginia Board of Examiners for Registered Professional Nurses, Provider Number WV97-0217R for 1 contact hour 45
Slide 46 SOURCE LIST Allison PR, Johnstone AS (June 1953). The oesophagus lined with gastric mucous membrane. Thorax 8 (2): 87 101. Barrett NR (October 1950). "Chronic peptic ulcer of the oesophagus and 'esophagitis'". Br J Surg 38 (150): 175 82 Barrett NR (June 1957). "The lower esophagus lined by columnar epithelium". Surgery 41 (6): 881 94. Cadiere GB, Rajan A. Rqibate M, et al. Endoluminal fundoplication (ELF) evolution of Esophyx, a new surgical device for transoral surgery. Minim Invasive Therapy Allied Technology. 2006; 15: 348-355 Fastest Rising Form of Cancer in the U.S. Webmd.com. 2005. WebMD. www.webmd.com/cancer/news/20050118/esophageal-cancer-on-rise Accessed October 2007. Fleischer DE, Overholt BF, Sharma VK, et al. Endoscopic Radiofrequency Ablation for Barrett s Esophagus: Five-Year Durability Outcomes from a Prospective Multi-Center Trial. Gastrointest Endosc 2010;71:AB117-118 Gerson LB, Shetler K, and Triadafilopoulos G. Prevalence of Barrett s esophagus in asymptomatic individuals. Gastroenterology 2002;123:461-467 G.M. Eisen. Ablation therapy for Barrett's esophagus. Gastrointestinal Endosc. 2003; 58: 760-769. 46 Slide 47 SOURCE LIST Heiko Pohl and H.G. Welch. The role of over diagnosis and reclassification in the Marked Increase of esophageal adenocarcinoma incidence. J Natl Cancer Inst. 2005: 97: 142-146. Pohl H, Welch HG. Natl Cancer Inst 2005 Pouw RE, Gondrie JJ, Rygiel AM, et al. Properties of the neosquamous epithelium after radiofrequency ablation of Barrett s esophagus containing neoplasia. Am J Gastroenterol 2009;104:1366-1373. Reid B.J and Weinstein W. M. Barrett's esophagus and adenocarcinoma. Gastroenterology Clinics of North America 1987; 38: 477-492. Ronkainen J, Aro P, Storskrubb T, et al. Prevalence of Barrett s esophagus in the general population: an endoscopic study. Gastroenterology 2005; 129:1825-1831. Shaheen N, Ransohoff DF. Gastroesophageal reflux, Barrett s esophagus and esophageal cancer. Journal of the American Medical Association. 2002; 287: 1972-1981. Shaheen NJ, Sharma P, Overholt BF, Wolfsen HC, Sampliner RE, Wang KK, Galanko JA, Bronner MP, Goldblum JR, Bennett AE, Jobe BA, Eisen GM, Fennerty MB, Hunter JG, Fleischer DE, Sharma VK, Hawes RH, Hoffman BJ, Rothstein RI, Gordon SR, Mashimo H, Chang KJ, Muthusamy VR, Edmundowicz SA, Spechler SJ, Siddiqui AA, Souza RF, Infantolino A, Falk GW, Kimmey MB, Madanick RD, Chak A, Lightdale CJ. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med. 2009 May 28;360(22): 2277-88 47 Slide 48 SOURCE LIST Sharma P, Falk GW, Weston AP, Reker D, Johnston M, Sampliner RE. Dysplasia and Cancer in a Large Multicenter Cohort of Patients with Barrett s Esophagus. Clinical Gastroenterology and Hepatology 2006;4:566-572. Spechler SJ, Goyal RK (February 1996). "The columnar-lined esophagus, intestinal metaplasia, and Norman Barrett". Gastroenterology 110 (2): 614 21 Study provides first estimate of U.S. population affected by Barrett s esophagus. Gastro.org. 2006. American Gastroenterological Association. Accessed August 2007. "What Are the Key Statistics about Cancer of the Esophagus?" Cancer.org. 2006. American Cancer Society. Accessed October 2007. Wani S, Puli SR, Shaheen NJ, Westhoff B, Slehria S, Bansal A, Rastogi A, Sayana H, Sharma P. Esophageal adenocarcinoma in Barrett's esophagus after endoscopic ablative therapy: a meta-analysis and systematic review. Am J Gastroenterol. 2009 Feb;104(2):502-13 Westhoff B, Brotze S, Weston A, et al. The frequency of Barrett s esophagus in high-risk patients with chronic gerd. Gastrointestinal Endosc. 2005; 61:226-231. What Are the Key Statistics about Cancer of the Esophagus?" Cancer.org. 2006. American Cancer Society. Accessed October 2007.. 48