1. Management of Barrett ’ s Esophagus Joint Hospital Surgical Grand Ground 17 th July 2010 Dr KS Chan Queen Elizabeth Hospital

2. Barrett ’ s Esophagus Metaplastic change in the distal esophageal lining Normal squamous epithelium replaced by columnar epithelium Named after Dr Norman Rupert Barrett  Incorrect description  “Congenitally short esophagus with tubular intrathoracic stomach” First description by Wilder Tileston dated back to 1906 Norman Rupert Barrett (1903–1979)

3. Prevalence  1.6-5.6% in general population  10-15% in patients with reflux symptoms Premalignant condition Associated with esophageal adenocarcinoma  0.5-1% per patient-year  30-40 fold increased risk compared to general population  10-15% per patient-year in BE with high grade dysplasia

4. Risks factor Gastroesophageal reflux Obesity Male sex Advanced age White race

5. Diagnosis White light endoscopy  Salmon-coloured epithelium projects into the tubular esophagus Systematic biopsy  4 quadrant biopsies every 2cm in the columnar segment  Additional biopsies from any mucosal abnormalities or visible lesions

6. Advances in Imaging High resolution white light microscopy Chromoendoscopy Narrow band imaging Autofluorescence imaging Confocal laser endomicroscopy Spectroscopy

7. Management Most patient with Barrett’s esophagus do not progress Confirm the diagnosis Non-dysplastic disease or low grade dysplasia  Managed conservatively High grade dysplasia  Increase risks of progression to cancer  Intervention advocated

8. Treatment of Barrett ’ s Esophagus Anti-reflux treatment  Proton Pump Inhibitor  Fundoplication Endoscopic Therapy  Ablative: Photodynamic therapy, Argon plasma coagulation, laser, cryotherapy, radiofrequency ablation, mutlipolar electrocautery  Resection: Endoscopic mucosal resection, Endoscopic submucosal dissection Surgical Therapy  Esophagectomy

9. Photodynamic Therapy Most extensively studied Use of photosensitizer which acculumates in malignant and pre-malignant tissue  Porfimer sodium, aminolevulinic acid Exposure to light of appropriate wavelength Production of singlet oxygen and reactive oxygen species Cell damage and apoptosis

11. 69% of the subjects who received PDT developed photosensitivity reactions 36% developed esophageal strictures that required dilation therapy First RCT showing reduction in adenocarcinoma risks in BE patients with any therapeutic intervention 5-ALA better tolerated with fewer complications

12. Radiofrequency Ablation High power radiofrequency energy generator, sizing balloon catheters and ablation catheters Penetration 0.5mm

13. Treatment repeated every 2-3 months All visible BE eradicated After final treatment session, biopsy taken over the original BE segment to exclude buried Barrett’s

15. Promising treatment modality Side effect  Esophageal stricture, GI bleeding and chest pain Substantially lower than those in photodynamic therapy Long term data needed

16. Endoscopic Resection Endoscopic Mucosal Resection (EMR) and Endoscopic submucosal dissection (ESD) Provide specimen for histopathological assessment Size of specimen resected by EMR limited to ~2cm each attempt ESD enable en bloc resection of lesion regardless of size

17. EMR “Suck and cut” method Complications  Bleeding  Perforation  Stricture

18. Endoscopic Therapy No single therapy achieve complete eradication without complications Recurrence Buried metaplasia  Partially ablated Barrett’s epithelium healed with overlying squamous epithelium Applicable to lesion confined to mucosa only  Breach muscularis mucosae, >20% LN metastasis

19. Surgical Treatment Esophagectomy considered as the ‘gold standard’ for high grade dysplasia and early adenocarinoma Morbidity and mortality Reported mortality rate ranges from 2% (Reed 2005), up to 20% post-operatively (Urba 2001)

20. Which is the best treatment? Currently no randomized controlled trials Only 6 restrospective, non-randomized trials  All with no significant difference in survival Difficult to draw definitive conclusion Should be individualized Considering age, co-morbidities, life expectancy and extent of disease

21. Conclusion Barrett’s esophagus is a pre-malignant condition Diagnosis relies on both endoscopic and histological findings Management should be based on risks stratification Emerging evidence on the use of endoscopic therapy Treatment should be individualized

23. Thank You

24. Diagnostic Criteria American College of Gastroenterology  Displacement of squmocolumnar junction proximal to the gastroesophageal junction  Evidence of specialized intestinal metaplasia on histology British Society of Gastroenterology  Endoscopically apparent area above the esophagogastric junction that is suggestive of Barrett esophagus  Supported by findings of columnar lined esophagus on histology

25. Gastroesophageal junction Proximal border of gastric folds during minimal insufflation Distal end of the lower esophageal palisade vessels

26. Prague Classification Circumference (C) Maximum extent (M) High degree of overall validity when Barrett’s segment > 1cm  Overall reliability coefficient of 0.72 Allow tracking of the length of BE segment

27. Anti-reflux treatment Aims for symptoms control and prevention of BE progression PPI decreases risks of dysplasia Concern of hypergastrinemia with the use of PPI Metaanalysis found no difference between fundopilcation and medical treatment in prevention of adenocarcinoma

28. Cancer incidence in surgical group 3.8/1000 patient-year; 5.3 in medical group (p=0.29) In recent 5 years, 3.8/1000 patient-year in surgical group vs 4.2 in medical group

29. Treatment of Barrett ’ s Esophagus Anti-reflux treatment  Proton Pump Inhibitor  Fundoplication Endoscopic Therapy  Ablative: Photodynamic therapy, APC, laser, cryotherapy, RFA, mutlipolar electrocautery  Resection: EMR, ESD Surgical Therapy  Esophagectomy Chemoprevention

31. Increased COX-2 expression in BE Protective effect seen with use of aspirin/NSAIDs and esophageal cancer in epidemiological studies Prospective trial with no impressive results (CBET Trial) Aspirin Esomeprazole ChemoPrevention (AspECT) Trial undergoing

32. Nine studies (2 cohort, 7 case control) containing 1813 cancer Protective association between any use of aspirin/NSAID and esophageal cancer (odds ratio [OR] 0.57; 95% confidence interval [CI], 0.47–0.71).