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Barretts Esophagus: Surveillance Modalities and Treatment Option Panorama

Barretts Esophagus: Surveillance Modalities and Treatment Option Panorama. Adam Elfant MD Associate Professor of Medicine Robert Wood Johnson Medical School Camden, NJ. Introduction . Significant advances in the area of Barretts Esophagus Increasingly recognized

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Barretts Esophagus: Surveillance Modalities and Treatment Option Panorama

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  1. Barretts Esophagus: Surveillance Modalities and Treatment Option Panorama Adam Elfant MD Associate Professor of Medicine Robert Wood Johnson Medical School Camden, NJ

  2. Introduction • Significant advances in the area of Barretts Esophagus • Increasingly recognized • Major risk factor for esophageal adenocarcinoma • Increasing incidence

  3. Epidemiology • Incidence : NCl rates outpace melanoma, breast and prostate cancer • Recent phenomenon: decreased rates in patients more than 85 years old (50%), unlike squamous cell Pohl H et al. JNCL 2005;97(2): 142-46

  4. Criteria for Barretts Esophagus • No universal agreement on inclusion of IM • Yield of IM decreases with fewer biopsies • Minimum number is eight biopsies • Establish presence of IM before committing to diagnosis and surveillance • No data on risk of EAC without IM Harrison R et al. Am J Gastro 2007; 102: 154-61

  5. Prague Classification • Landmarks: • Squamocolumnar junction • GE junction • Extent of circumferential columnar lining • Proximal extension of columnar lining Sharma et al. Gastro 2006;131:1392-99

  6. Screening • Caucasian males with chronic reflux. • Challenges: • Inability to predict who has Barretts esophagus • Lack of evidence based criteria • Expense of endoscopy • BE patients without reflux (44%) Ronkainen J. Gastro 2005;129: 1825-31

  7. Predictors for Barretts • Age >40 • Heartburn • Duration (>13 years) • Male gender • ? Obesity

  8. Obesity and Barretts • Increased risk of EAC and Barretts • BMI/ GERD are known risk factors correlated with BE • Meta-analysis (10 studies) Cook et al AJG 2008; 103: 292-300

  9. Surveillance • Controversial due to lack of RCT • Retrospective studies indicate survival advantage • Rationale for surveillance (5 year survival EAC: 13%)

  10. Surveillance • Erosive esophagitis: • Do not ignore the mucosa • Barretts metaplasia may be present in 12% of cases Hanna S et al. Am J Gastro 2006;101:1416-20

  11. Considerations • Age • Likelihood of 5 year survival • Compliance • Controlled reflux: • visual recognition • avoid cellular changes

  12. Technique • 4 quadrant biopsies every 2 cm • Turn and suction • Separate containers • 3 year surveillance interval (50% of HGD/EAC had negative EGD) Sharma P. Clin Gastro & Hepato 2006;4: 566-72

  13. Low Grade Dysplasia (LGD) • EGD within 6 months • Confirm LGD – expert • Yearly until 2 consecutive negative • Neoplastic progression • Majority have no dysplasia on 4 year follow up Skacel M. Am.J Gastro 2000;95: 3383-87

  14. High Grade Dysplasia (HGD) • Repeat EGD every 3 months • 5 year risk EAC > 30% • Treat based on highest grade dysplasia

  15. New Imaging Techniques • Narrow band • Autofluorescence • Methylene blue chromoendoscopy (+IM, --HGD/EC) • Laser confocal microscopy (94% accuracy) • Fluorescent in Situ Hybridization (Fish)

  16. Narrow Band Imaging • Commercially available • Filters light to Blue/Green • Differential Absorption by vessels • Sensitivity 100% • Specificity 98.7% Sharma P. Gastrointest. Endosc 2006; 64(2): 167-75

  17. Autofluorescence • Blue light illumination • Detects fluorescence of cellular components • Performed with contact optical fiber probe • Dysplasia < normal tissue • Suitable for screening large areas • High false positives (40%) Kara Ma. Gastrointest Endosc 2006; 64(2):176-85

  18. Methylene Blue Chromoendoscopy Unstained, irregular Z line Intensive methylene blue staining of a focal patch of Barrett epithelium. Rajan E. Mayo Clin Proc. 2001;76: 217-225

  19. Laser Confocal Microscopy (LCM) • Suitable for small areas mucosa • Magnify mucosa/ cellular structures • Accuracy 94% for neoplasia Kiesslich R . Clin Gastroentrol & hepatol 2006; 4(8): 979-87

  20. Fluorescent in Situ Hybridization • Malignancies have characteristic genetic alterations • Fluorescent labeled DNA probe for chromosomal abnormalities: probes assess deletions, gains or amplifications • 11 sites identified LGD, HGD and adenocarcinoma Brankley SM JMD 2006;8(2): 260-67

  21. FISH • 138 subjects, biopsies at 1 cm with EMR: Brankley SM JMD 2006;8(2): 260-67

  22. Biomarkers • Few studies performed • Nuclear DNA • Aneuploidy (RR: 9.5) • Tetraploidy (RR:11.7) • Loss of heterozygosity: gene P16, P53(RR:16) • Methylation genes RUNX3, HPPI, P16

  23. Biomarkers in BE Immunohistochemistry with the DO-7 antibody for the p53 protein in Barrett esophagus with low-grade dysplasia and normal squamous epithelium. Intense staining of the columnar epithelium (arrow 1) indicates accumulation of the p53 protein in nuclei. In normal squamous epithelium, p53-positive staining can be noticed in the basal (proliferating) layer (arrow 2). Mutation analysis did not show P53 gene mutations in either epithelia Kausilia K. Mayo Clin Proc. 2001;76: 438-446

  24. Management of BE with Dysplasia • Most appropriate management unclear • Society guidelines suggest competing strategies: • Intensified endoscopic surveillance • Esophagectomy • Endoscopic ablation

  25. Management of Dysplasia • Mucosal irregularity- Best assessed by endoscopic resection • Dependent local expertise • Age • Comorbidities • Preferences • Esophagectomy not automatic

  26. Management of HGD • 4 quadrant biopsies every 1 cm (50% miss rate). • ER HGD nodules: • Increased risk of cancer • Regional metastasis • Occult cancer still possible • Large capacity forceps: turn and suction technique Reid BJ. Am.J Gastro 2000;95: 3089-96 Buttar NS. Gastro 2001; 120:1630-9

  27. Potential Benefits of Ablation • HGD: prevent cancer, cure mucosal disease • LGD: prevent progression to HGD/ cancer • IM: • Prevent progression to HGD/ cancer • Lengthen surveillance • Reduce healthcare costs

  28. Endoscopic Ablation Techniques • APC • Multipolar Electrocoagulation • Lasers (Nd-Yag, KTP) • Endoscopic mucosal resection (EMR) • Photodynamic therapy (PDT) • Cryotherapy • Radiofrequency therapy

  29. EMR (HGD, EAC) • Outpatient procedure • Major risk : • Hemorrhage (<5%) • Perforation (<1%) • Pathology – tumor depth / margins

  30. EMR (HGD, EAC) • 64 patients ( 61 EAC and 3 HGD) • Group A < 2 cm, limited to mucosa • Group B > 2 cm, including submucosa Ell et al. Gastro 2000;118: 670-77

  31. EMR with Ligation Hoschler AH. Br J Surg;84: 1470-3

  32. EMR with Snare Resection Seewald S. Postgrad. Med J;83: 367-372

  33. Thermal Ablation (Laser, APC, MPEC) • Small trials • Multiple treatments • Similar results (80-90%) • Short follow up Byrne JP Am J Gastroenterol 1998; 93:1810-15 Dulai GS Gastrointest Endosc 2005; 61:232-40

  34. Argon Plasma Coagulation (APC) • High frequency monopolar current conducted via ionized Argon gas • Literature review of 444 patients (12 centers) • CR-BE: 38-98.6 % (F/U 12-51 months) • Subsquamous IM : 0-30% Sampliner RE Gastrointest Endosc. 2004; 59: 66-69

  35. APC

  36. APC Wolfsen H.Gastrointest. Endosc. Clin N Am 2007;17: 59-82

  37. Photodynamic Therapy (HGD) • Drug (photosensitive) • Porfimer sodium • 5-ALA • Light :Red light (630nm) carried via fiberoptic guide for drug activation • Photoradiating Balloons • Oxygen (ablation rxn) Brankley SM JMD 2006;8(2): 260-67

  38. Photodynamic Therapy Wolfsen H.Gastrointest. Endosc. Clin N Am 2007;17: 59-82

  39. Photodynamic Therapy • Only RCT of ablation to decrease cancer risk • 208 patients (2:1 randomization) HGD • PPI vs PDT +PPI • Primary outcome – Complete ablation HGD • Secondary outcome – Cancer development during study Overholt B. Gastrointest. Endosc 2005; 62: 488-98

  40. Results

  41. Cryospray Ablation • Requires cryogenic catheter (electrically warmed), liquid nitrogen spray (-196 °C) • Hemicircumferential, monthly, 4cm segments (n=11) • Complete reversal of BE in 9/11 (78%) • No subsquamous IM at 6 months • Low ambient pressure device (3-6 psi), monitors duration • Mean number of treatments 3.6 Johnston MH Gastrointest Endosc.2005;62(6): 842-8

  42. Cryospray Ablation

  43. Radiofrequency Ablation • High power, balloon based bipolar electrodes attached to radiofrequency generator • Rapid delivery (<1 sec) • Energy density control (9.7 -10.6 J/cm2) • Epithelium  muscularis mucosa

  44. Radiofrequency Ablation

  45. AIM Dysplasia Trial • Randomized sham controlled • 127 subjects (LGD,HGD) • 101 completed 12 months

  46. Results

  47. RFA (Circumferential / Focal) • 61 patients • circumferential with focal “clean up” • 2.5 years follow up • 60/61 completely cleared BE (CR=98%) • No stricture, buried BE (3930 biopsies) Fleicher DE, Gastrointest. Endosc 2007;65:AB135

  48. Post Ablative Therapy • Biopsy the entire area of prior Barretts • Interval based on prior grade dysplasia • 3 consecutive endoscopies • Periodic surveillance

  49. BE with HGD (Esophagectomy) • Frequency of EAC at resection (17%) • Operative mortality (4-7%) • Centers of excellence (1-2%) • Early morbidity (15-32%) • Late morbidity (>50%) • Possible recurrent IM and dysplasia Tseng EE J. gastrointest. Surg 2003;7: 164-71

  50. HGD: PDT+EMR vs Esophagectomy • 199 patients • Retrospective • No death due to EC • Mortality 9%vs 8.5% Prasad GA. Gastro 2007;132: 1226-33

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