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

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Presentation on theme: "Barrett’s surveillance: Is there a case? Peter D. Siersema."— Presentation transcript:

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: 633-40Detection 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 not surveillance-detected

4 Flow CYtometry in BARret esophagus (CYBAR study): a prospective cohort study M.Sikkema 1, M.Kerkhof 1, E.W. Steyerberg 2, H. van Dekken 3, A.J. van Vuuren 1, H.Geldof 4, H. van der Valk 5, R.J. Ouwendijk 6, R. Giard 7, W. Lesterhuis 8, R. Heinhuis 9, E.C. Klinkenberg 10, G.A.Meijer 11, F. ter Borg 12, J.W. Arends 13, J.J. Kolkman 14, J. van Baarlen 15, R.A. de Vries 16, A.Mulder 17, A. van Tilburg 18, G.J.A.Offerhaus 19, F.J.W. Ten Kate 19, J.G. Kusters 1, E.J. Kuipers 1 and P.D. Siersema 1 for the CYBAR study group Depts. of Gastroenterology and Hepatology, ErasmusMC Rotterdam 1, IJsselland Hospital Capelle a/d IJssel 4, Ikazia Hospital Rotterdam 6, Albert Schweizer Hospital Dordrecht 8, VUMC Amsterdam 10, Deventer Hospital Deventer 12, Medisch Spectrum Twente Enschede 14, Rijnstate Hospital Arnhem 16, Sint Franciscus Gasthuis Rotterdam 18 Depts of Public Health 2 and Pathology 3, ErasmusMC Rotterdam; PATHAN, Rotterdam 5, Depts of Pathology, MCRZ Rotterdam 7, Laboratory for Pathology Dordrecht 9, VUMC Amsterdam 11, Deventer Hospital Deventer 13, Pathology Laboratory Enschede 15, Rijnstate Hospital Arnhem 17, UMC Utrecht 19

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

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

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

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

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

12 Intra- and interobserver variability in grading dysplasia is great Kerkhof et al. Histopathology 2007; 50: 920-7Intra- and interobserver variability in grading dysplasia is great Kerkhof et al. Histopathology 2007; 50: 920-7 Barrett’s esophagus is an unlikely cause of death ( only 4 (6%) of 105 patients after a mean FU of 12.7 yrs.)Barrett’s esophagus is an unlikely cause of death ( only 4 (6%) of 105 patients after a mean FU of 12.7 yrs.) Hage et al. Scand J Gastroenterol 2004; 39: 1175-9 The majority of cost-effectiveness acceptability curves show that surveillance is unlikely to be cost- effectiveThe majority of cost-effectiveness acceptability curves show that surveillance is unlikely to be cost- effective Garside et al. Health Technol Assess 2007;11: iii-iv, ix-221 Barrett’s surveillance: CONTRA

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

14 Biomarkers in Barrett’s esophagus BiomarkerType of changePotential Use PCNAincreased expression with proliferation+ / - Ki67increased expression with proliferation+ p53IHC (abnormal protein expression)+ LOH (frequent LOH at 17p13)+ / - p16LOH at 9p21, early lesion- Cyclin D1increased expression- β-cateninincreased nuclear expression- decreased membranous expression DNA ploidyaneuploidy with progression+ COX-2increased expression- Kerkhof et al. Cell Oncol 2007; 29: 507-17

15 Diploid AneuploidTetraploid G1 S S S G2/M (normal) (abnormal) Flow cytometry

16 2 yr cum risk of progression 1.9% 1.9% 1.3% 1.3% 11.9% 11.9% 20% 20% Log Rank p=0.19 p=0.19 p=0.50 p=0.50 703 patients with BE ≥ 2 cm Baseline ND n = 604Baseline LGD n = 99 FC normal n=471 FC abnormal n=78 FC normal n=84 FC abnormal n=15 Risk per surveillance arm one progression observed in pts without FC analysis: 1/52 = 1.9%

17 Retrospective study BE with progression towards HGD/EAC BE without progression towards HGD/EAC n = 27n = 28 Other biomarkers

18 Biopsies Histology (H&E) IHC: p53-staining Ki67-staining p53 Ki67 Biomarkers

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

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

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

22 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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