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Barrett’s surveillance: Is there a case? Peter D. Siersema

Barrett’s surveillance: Is there a case? Peter D. Siersema. Wang et al. Am J Gastroenterol 2008: 103:788-97. Barrett’s surveillance: PRO. Detection of adenocarcinoma at an earlier stage, .... Corley DA, et al. Gastroenterology 2002; 122: 633-40 Cooper GS, et al. Cancer 2002; 95: 32-8

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Barrett’s surveillance: Is there a case? Peter D. Siersema

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  1. Barrett’s surveillance: Is there a case? Peter D. Siersema

  2. Wang et al. Am J Gastroenterol 2008: 103:788-97

  3. Barrett’s surveillance: PRO • Detection of adenocarcinoma at an earlier stage, ....Corley DA, et al. Gastroenterology 2002; 122: 633-40 Cooper GS, et al. Cancer 2002; 95: 32-8 Kearney DJ, et al. Gastrointest Endosc 2003; 57: 823-9 Fountoulakis, et al. Br J Surg 2004; 91: 997-1003 surveillance-detected not surveillance-detected

  4. Flow CYtometry in BARret esophagus (CYBAR study): a prospective cohort study M.Sikkema1, M.Kerkhof1, E.W. Steyerberg2, H. van Dekken3, A.J. van Vuuren1, H.Geldof4, H. van der Valk5, R.J. Ouwendijk6, R. Giard7, W. Lesterhuis8, R. Heinhuis9, E.C. Klinkenberg10, G.A.Meijer11, F. ter Borg12, J.W. Arends13, J.J. Kolkman14, J. van Baarlen15, R.A. de Vries16, A.Mulder17, A. van Tilburg18, G.J.A.Offerhaus19, F.J.W. Ten Kate19, J.G. Kusters1, E.J. Kuipers1 and P.D. Siersema1 for the CYBAR study group Depts. of Gastroenterology and Hepatology, ErasmusMC Rotterdam1, IJsselland Hospital Capelle a/d IJssel4, Ikazia Hospital Rotterdam6, Albert Schweizer Hospital Dordrecht8, VUMC Amsterdam10, Deventer Hospital Deventer12, Medisch Spectrum Twente Enschede14, Rijnstate Hospital Arnhem16, Sint Franciscus Gasthuis Rotterdam18Depts of Public Health2 and Pathology3, ErasmusMC Rotterdam; PATHAN, Rotterdam5, Depts of Pathology, MCRZ Rotterdam7, Laboratory for Pathology Dordrecht9, VUMC Amsterdam11, Deventer Hospital Deventer13, Pathology Laboratory Enschede15, Rijnstate Hospital Arnhem17, UMC Utrecht19

  5. Barrett’s surveillance: CYBAR study N=17 (71%) N=703, FU: 3 yrs, progression to HGD: 14 or EAC: 10

  6. Barrett’s surveillance: PRO • ….. resulting in improved survival ratesCorley DA, et al. Gastroenterology 2002; 122: 633-40 Fountoulakis, et al. Br J Surg 2004; 91: 997-1003

  7. Barrett’s surveillance: PRO • Barrett’s patients report less discomfort, pain and overall burden than patients with non-specific GI symptoms or esophageal cancerKruijshaar, et al.Qual Life Res 2007; 16:1309-18

  8. Barrett’s surveillance: PRO • Surveillance at 2-year intervals would cost £19,000 per live saved Armstrong. Best Pract Res Clin Gastroenterol 2008; 22: 721-39

  9. Barrett’s surveillance: PRO • Surveillance at 2-year intervals would cost £19,000 per live saved Armstrong. Best Pract Res Clin Gastroenterol 2008; 22: 721-39 • More and less invasive treatment strategies are available for HGD and early adenocarcinoma (T1m1-3, sm1)

  10. Barrett’s surveillance: PRO • Surveillance at 2-year intervals would cost £19,000 per live saved Armstrong. Best Pract Res Clin Gastroenterol 2008; 22: 721-39 • More and less invasive treatment strategies are available for HGD and early adenocarcinoma (T1m1-3, sm1) • As current guidelines recommend a surveillance strategy, legal aspects need to be considered

  11. Is surveillance of Barrett’s esophagus with endoscopy indeed without discussion?

  12. Barrett’s surveillance • Imaging modalities to aid in detecting dysplasia • NBI, FICE, Autofluorescence, Chromoendoscopy • Confocal endomicroscopy, Endocytoscopy • Chemoprevention to prevent progression towards malignancy in BE (ASPECT study) • Biomarkers to detect the subgroup of patients with an increased risk of developing malignancy in BE

  13. Biomarkers in Barrett’s esophagus Biomarker Type of change Potential Use PCNA increased expression with proliferation + / - Ki67 increased expression with proliferation + p53 IHC (abnormal protein expression) + LOH (frequent LOH at 17p13) + / - p16 LOH at 9p21, early lesion - Cyclin D1 increased expression - β-catenin increased nuclear expression - decreased membranous expression DNA ploidy aneuploidy with progression + COX-2 increased expression - Kerkhof et al. Cell Oncol 2007; 29: 507-17

  14. Flow cytometry Diploid (normal) G1 G2/M S Aneuploid Tetraploid G1 G1 (abnormal) (abnormal) S G2/M G2/M S

  15. Risk per surveillance arm 703 patients with BE ≥ 2 cm Baseline ND n = 604 Baseline LGD n = 99 FC normal n=471 FC abnormal n=78 FC normal n=84 FC abnormal n=15 one progression observed in pts without FC analysis: 1/52 = 1.9%

  16. Other biomarkers Retrospective study BE withoutprogression towards HGD/EAC BE withprogression towards HGD/EAC n = 27 n = 28

  17. Biomarkers Biopsies Histology (H&E) IHC: • p53-staining • Ki67-staining p53 Ki67

  18. Results HGD/EAC + Fraction LGD HGD/EAC - -15 -10 -5 0 Years before HGD/EAC

  19. Results HGD/EAC + Fraction LGD Fraction Ki67 expression HGD/EAC - -15 -10 -5 0 Years before HGD/EAC -15 -10 -5 0 Years before HGD/EAC

  20. Results Fraction LGD Fraction Ki67 expression -15 -10 -5 0 Years before HGD/EAC -15 -10 -5 0 Years before HGD/EAC HGD/EAC + Fraction p53 expression HGD/EAC - -15 -10 -5 0 Years before HGD/EAC

  21. Barrett’s surveillance: Is there a case? YES, but this should: not only be based on histology, but also include a panel of easy to use biomarkers, that is able to select the small group of Barrett’s patients at risk of progressing to malignancy

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