DISCLOSURES. This program meets the requirements for GI specific Category 1 contact hours. M

Transcription

1 DISCLOSURES Educational Dimensions is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center s Commission on Accreditation. Successful completion: Participants must attend the entire program, including any resulting Q & A, and submit required documentation. Conflict of interest: Planners disclose no conflict of interest; the speaker discloses a relationship with the supporting company. The speaker has signed a statement agreeing to present information fairly and without bias. Commercial company support: Fees are underwritten by education funding provided by Covidien-GI Solutions. Non-commercial company support: None. Alternative or Complementary Therapy: None. This program meets the requirements for GI specific Category 1 contact hours. 1

2 DIAGNOSIS AND TREATMENT 2

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

4 OBJECTIVES Describe the disease process for Barrett's esophagus Contrast various approaches to managing Barrett s esophagus 4

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): Allison PR, Johnstone AS (June 1953). The oesophagus lined with gastric mucous membrane. Thorax 8 (2): Barrett NR (June 1957). "The lower esophagus lined by columnar epithelium". Surgery 41 (6): Spechler SJ, Goyal RK (February 1996). "The columnar-lined esophagus, intestinal metaplasia, and Norman Barrett". Gastroenterology 110 (2):

6 WHAT IS BARRETT S ESOPHAGUS? Image: ablation1.jpg Image: 6

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: 7

8 CAUSE OF INTESTINAL METAPLASIA BARRETT S ESOPHAGUS A response to chronic exposure of gastric acid Cells of the esophageal lining undergo changes in organization Results in formation of Intestinal Metaplasia (Barrett s esophagus) 8

9 ESOPHAGEAL HISTOLOGY Esophageal Epithelium ~500µm Lamina Propria Muscularis Mucosae ~1000µm Submucosa Muscularis Propria Image: 9

10 STAGES OF BARRETT S ESOPHAGUS Non Dysplastic Intestinal Metaplasia (NDIM) Indefinite Low-Grade Dysplasia High-Grade Dysplasia Barrett s Esophagus left untreated could lead to Intramucosal Carcinoma (Adenocarcinoma) Fleischer DE, Odze R, et al. The Case for Endoscopic Treatment of Non-dysplastic and Low-Grade Dysplastic Barrett s Esophagus, Dig Dis Sci DOI /s

11 CAN YOU TELL WHAT STAGE THESE HISTOLOGY SLIDES SHOW? Inter-observer agreement is moderate at best, and in some studies it is poor 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 Non-dysplastic 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 /s Image from: Huang Q, et al. BMC Clin Pathol Aug 12;5:7

12 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 )

13 EVOLUTION OF BARRETT S AND CANCER Squamous esophagus Injury Acid & bile reflux nitrous oxide Chronic inflammation Barrett's metaplasia Genetics Gender, race, & other factors (cox-2) Low-grade dysplasia High-grade dysplasia Invasive Adenocarcinoma Accumulate Genetic Changes Morales CP et al. Lancet 2002; 360: Sharma P, Falk GW, Weston AP, et al. Dysplasia and cancer in a large multicenter cohort of patients with Barrett s esophagus. Clin Gastroenterol Hepatol 2006; 4:

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:

15 RELATIVE CHANGE IN ESOPHAGEAL ADENOCARCINOMA INCIDENCE Esophagus Melanoma Prostate Lung/Breast Colorectal From: Pohl H, Welch HG. Natl Cancer Inst

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: Gerson LB, Shetler K, and Triadafilopoulos G. Prevalence of Barrett s esophagus in asymptomatic individuals. Gastroenterology 2002;123:

17 BARRETT S PREVALENCE ESTIMATES 1.6% of general adult population (3.3 M) Ronkainen J, et al. Prevalence of BE Gastroenterology 2005;129: % 5.6% of general adult population ( M) Tristan J, et al. The Prevalence of BE in the US (model)...ddw Hayeck TJ, et al. The Prevalence of BE in the US (model) Dis Esophagus 2010;23: % of persons over age 40 (8.7 M) Rex DK, et al. Screening for Barrett s... Gastroenterology 2003; 125:

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 C. Thermal Cryotherapy Circumferential and Focal RFA Sharma P. Strategies and recommendations for diagnosing and managing Barrett's esophagus Dec 31, 2009 New England Journal of Medicine. 18

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 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 < 19

20 HUMAN ESOPHAGUS Esophageal mucosa Biopsy depth Submucosa with esophageal G glands G Muscularis mucosa Muscularis propria. Image: Prateek Sharma, M.D.. N Engl J Med 361;26 NEJM.org December 24,

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%. Luna RA, Gilbert E, Hunter JG. High-grade dysplasia and intramucosal adenocarcinoma in Barrett's esophagus: the role of esophagectomy in the era of endoscopic eradication therapy. Curr Opin Gastroenterol 2012;28: Markar SR, Karthikesalingam A, Low DE. Outcomes assessment of the surgical management of esophageal cancer in younger and older patients. Ann Thorac Surg 2012;94:

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. 22

23 ENDOSCOPIC MUCOSAL RESECTION (EMR) One Technique: Several Techniques 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: 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; 23

24 ENDOSCOPIC MUCOSAL RESECTION (EMR) Advantages:I 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 mages: 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

25 HUMAN ESOPHAGUS Esophageal Mucosa Image: Submucosa with esophageal G glands G Muscularis mucosa EMR Depth Radical EMR CR-D : 100% CR-IM : 92% Strictures: 88% # Therapeutic Sessions: 6 Muscularis propria Esophagectomy Operative mortality rate of 3-12% 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

26 Indications ARGON PLASMA COAGULATION 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 Image: 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

27 HUMAN ESOPHAGUS Esophageal mucosa Image: 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% Muscularis propria Multiple cases of adenocarcinoma arising under the squamous reepithelialization have been observed after APC. Deviere J. Argon plasma coagulation therapy for ablation of Barrett s oesophagus Gut December; 51(6): Menon et al. Endoscopic treatments for Barrett s esophagus: a systematic review of safety and effectiveness compared to esophagectomy BMC Gastroenterology 2010, 10:

28 Indications Goal: PHOTODYNAMIC THERAPY High-Grade Dysplasia (HGD) Barrett's esophagus Eliminate HGD using an endoscopic therapy rather than surgical esophagectomy PDT 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: 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);

29 HUMAN ESOPHAGUS Esophageal mucosa Image: 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% Muscularis propria Photosensitivity: 26.4% Menon et al. Endoscopic treatments for Barrett s esophagus: a systematic review of safety and effectiveness compared to esophagectomy BMC Gastroenterology 2010, 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 /aja 2011: 255[epub ahead of print] 29

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 Wang KK, Nijhawan PK. Complications of photodynamic therapy in gastrointestinal disease. Gastrointest Endosc Clin N Am 2000; 10: 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);

31 Indications Goal: 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 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

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 April ; 71(4): doi: /j.gie CRYOTHERAPY One retrospective study of 98 patients reported 60 patients completed the therapy 58 patients had complete response to removing HGD=97%, BUT Submucosa with esophageal G glands G Muscularis mucosa) of those, 52 of them had showed only downgrading of histology: 87% HGD to Non-Dysplastic, not a complete removal of disease. Muscularis propria 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: 32

33 Advantages: CRYOTHERAPY Able to treat large, or stricture areas Coating of ice creates a whitened appearance Thru the scope device Limitations and possible complications: User variability Gastric distention Limited support in the 2011 AGA position statement Limited data, no RCT Image: AGA Institute Medical Position Panel, Gastro,

34 RADIOFREQUENCY CIRCUMFERENTIAL AND FOCAL ABLATION Fleischer DE et al. Endoscopic Ablation of BE a multicenter study with 2.5 year follow-up GIE 2007 Fleischer DE, et al. Endoscopic Radiofrequency Ablation for Barrett s Esophagus: Five-Year Durability Outcomes from a Prospective Multi-Center Trial. GIE Indications Goal: Barrett s esophagus Non-nodular, NDIM, LGD and HGD 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 Shaheen NJ, et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med May 28;360(22):

35 RADIOFREQUENCY CIRCUMFERENTIAL AND FOCAL ABLATION Technique: Endoscopic evaluation of Barrett s extent Size Ablate with visual placement Clean Repeat 35

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. 90+ publications Ablation Target Submucosa with esophageal G glands Muscularis propria Image: G Circumferential and Focal RFA Controlling ablation depth minimizes complications Muscularis mucosa (Ablation Target Depth) Fleischer DE et al. Endoscopic Ablation of BE a multicenter study with 2.5 year follow-up GIE 2007 Fleischer DE, et al. Endoscopic Radiofrequency Ablation for BE: Five-Year Durability Outcomes from a Prospective Multi-Center Trial. GIE 2010 Shaheen NJ, et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med May 28;360(22): Shaheen, et al. Durability of Radiofrequency Ablation in Barrett s Esophagus with Dysplasia. Gastroenterology

37 RADIOFREQUENCY ABLATION Limitations and possible complications Therapeutic procedural time (28-36 minutes for Circumferential and 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 ~ μm 90+ clinical publications Safety and efficacy to 5 years Clinical reports of > 90% CR-IM and CR-D Post-RFA: 2-5 years Fleischer DE,et al. Endoscopic Ablation of BE a multicenter study with 2.5 year follow-up GIE Fleischer DE, et al. Endoscopic Radiofrequency Ablation for BE: Five-Year Durability Outcomes from a Prospective Multi-Center Trial. GIE 2010 Shaheen NJ, Sharma P, Overholt BF, et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med May 28;360(22): Baseline Circumferential ablation 37

38 HUMAN ESOPHAGUS Ablation Target Circumferential and Focal RFA APC, PDT, CRYO Submucosa with esophageal G glands G Controlling ablation depth minimizes complications EMR Depth Muscularis propria Muscularis mucosa (Ablation Target Depth) Surgical Depth Image: 38

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: 39

40 THE 2011 AGA MEDICAL POSITION STATEMENT SUGGESTS RFA AS AN OPTION FOR BARRETT S ESOPHAGUS PATIENTS AGA Medical Position Statement (Gastroenterology 2011;140: ) HGD: Endotherapy with RFA, PDT, or EMR is recommended rather than surveillance LGD: RFA should be a therapeutic option for treatment of patients with confirmed LGD NDBE: 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,

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 ASGE Standards of Practice Committee. Guideline - Role of endoscopy in BE and other premalignant conditions of the esophagus. GIE 2012

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 ASGE Standards of Practice Committee. Guideline - Role of endoscopy in BE and other premalignant conditions of the esophagus. GIE

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

44 CONCLUSION OF MODULE This concludes the CNE educational activity Understanding Barrett's Esophagus. Please turn in your completed evaluations. 44

45 ACCREDITATION Educational Dimensions is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's Commission on Accreditation. One contact hour will be awarded to participants successfully completing the entire activity, including any question and answer session. Provider approved by: California Board of Registered Nursing, Provider Number District of Columbia Board of Nursing, Provider Number Florida Board of Registered Nursing, Provider Number Iowa Board of Nursing, Provider Number 317 West Virginia Board of Examiners for Registered Professional Nurses, Provider Number WV R 45

46 SOURCE LIST Allison PR, Johnstone AS (June 1953). The oesophagus lined with gastric mucous membrane. Thorax 8 (2): Barrett NR (October 1950). "Chronic peptic ulcer of the oesophagus and 'esophagitis'". Br J Surg 38 (150): Barrett NR (June 1957). "The lower esophagus lined by columnar epithelium". Surgery 41 (6): 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: Deviere J. Argon plasma coagulation therapy for ablation of Barrett s oesophagus Gut December; 51(6): Eisen GM. Ablation therapy for Barrett's esophagus. Gastrointestinal Endosc. 2003; 58: Fastest Rising Form of Cancer in the U.S. Webmd.com WebMD. Accessed October Fleischer DE et al. Endoscopic Ablation of BE a multicenter study with 2.5 year follow-up GIE Fleischer DE, et al. Endoscopic Radiofrequency Ablation for BE: Five-Year Durability Outcomes from a Prospective Multi- Center Trial. Gastrointest Endosc 2010;71:AB Fleischer DE, Odze R, et al. The Case for Endoscopic Treatment of Non-dysplastic and Low-Grade Dysplastic Barrett s Esophagus, Dig Dis Sci DOI /s Gerson LB, Shetler K, and Triadafilopoulos G. Prevalence of Barrett s esophagus in asymptomatic individuals. Gastroenterology 2002;123: Gray NA, Odze RD, Spechler SJ., Buried metaplasia after Endoscopic Ablation of Barrett's Esophagus: a Systematic Review. AM J Gastroenterology, 2011 Aug 9, doi /aja 2011: 255[epub ahead of print] 46

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: Luna RA, Gilbert E, Hunter JG. High-grade dysplasia and intramucosal adenocarcinoma in Barrett's esophagus: the role of esophagectomy in the era of endoscopic eradication therapy. Curr Opin Gastroenterol 2012;28: Markar SR, Karthikesalingam A, Low DE. Outcomes assessment of the surgical management of esophageal cancer in younger and older patients. Ann Thorac Surg 2012;94: Menon et al. Endoscopic treatments for Barrett s esophagus: a systematic review of safety and effectiveness compared to esophagectomy BMC Gastroenterology 2010, 10:111 Morales CP et al Hallmarks of CA progression in BO, Lancet 2002 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); 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:

48 SOURCE LIST Reid B.J and Weinstein W. M. Barrett's esophagus and adenocarcinoma. Gastroenterology Clinics of North America 1987; 38: Ronkainen J, Aro P, Storskrubb T, et al. Prevalence of Barrett s esophagus in the general population: an endoscopic study. Gastroenterology 2005; 129: Shaheen N, Ransohoff DF. Gastroesophageal reflux, Barrett s esophagus and esophageal cancer. Journal of the American Medical Association. 2002; 287: Shaheen NJ, Sharma P, Overholt BF, et al. Radiofrequency ablation in Barrett's esophagus with dysplasia. N Engl J Med May 28;360(22): Shaheen, et al. Durability of Radiofrequency Ablation in Barrett s Esophagus with Dysplasia. Gastroenterology 2011 Shaheen NJ, MD, MPH, and Greenwald, G et al. Safety and efficacy of endoscopic spray cryotherapy for Barrett s esophagus with high-grade dysplasia. Gastrointest Endosc April ; 71(4): doi: /j.gie 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: Sharma P. Strategies and recommendations for diagnosing and managing Barrett's esophagus Dec 31, 2009 New England Journal of Medicine. 48

49 SOURCE LIST Spechler SJ, Goyal RK (February 1996). "The columnar-lined esophagus, intestinal metaplasia, and Norman Barrett". Gastroenterology 110 (2): Study provides first estimate of U.S. population affected by Barrett s esophagus. Gastro.org American Gastroenterological Association. Accessed August 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 Wang KK, Nijhawan PK. Complications of photodynamic therapy in gastrointestinal disease. Gastrointest Endosc Clin N Am 2000; 10: 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 Feb;104(2): 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: What Are the Key Statistics about Cancer of the Esophagus?" Cancer.org.. American Cancer Society. Accessed October MEDICAL SOCIETIES POSITION STATEMENTS AGA Institute Medical Position Panel, Gastroenterology 2011;140: ASGE Standards of Practice Committee. Guideline - Role of endoscopy in BE and other premalignant conditions of the esophagus. GIE 2012 SAGES Guideline Stefanidis, Surg Endosc,