optical diagnosis and treatment in barrett s esophagus

1. Dr Laurence Lovat National Medical Laser Centre University College London, UK

2. Esophageal Cancer Rates (Men, Age Standardised Mortality/105)

3. Esophageal Cancer Rates (Men, Age Standardised Mortality/105)

4. Esophageal Cancer Rates (Men, Age Standardised Mortality/105)

5. The Questions How do we prevent death from esophageal adenocarcinoma? How do we detect patients at risk? How do we best treat patients?

6. The Questions How do we prevent death from esophageal adenocarcinoma? How do we detect patients at risk? How do we best treat patients?

7. Detecting patients at risk 80% of cases of esophageal adenocarcinoma arise within Barrett�s esophagus Screening Endoscopy Invasive Not of proven value Less invasive techniques Nothing proven

8. Detecting patients at risk Surveillance Lifetime risk of cancer <10% Need to target high risk groups

9. Markers of Risk

10. Cancer Risk in Presence of Aneuploidy or Tetraploidy >6%

11. p16, p53, ploidy Biomarker Panel Progression to EA

12. Endoscopic Detection of HGD

13. Morphological Changes in HGD

14. Elastic Scattering Spectroscopy(�Optical biopsy�) Point measurement Wavelength dependence Scattering efficiency of tissue Sensitive to morphological changes Size, shape and density of nuclei & mitochondria cellular density

15. Elastic Scattering Spectroscopy

16. Optical Biopsy

17. Elastic Scattering Spectra Separate evidence in vitrofrom rat fibroblasts that amound of genetic material in cells affects the slope between 630 and 820 nmSeparate evidence in vitrofrom rat fibroblasts that amound of genetic material in cells affects the slope between 630 and 820 nm

19. ESS �Optical Biopsies� Perform 17 random biopsies OR 17 optical measurements and 7 biopsies Model: 92% dysplasia sites detected Negative test >99.5% reliable

20. Taking Optical Biopsy Forward Detecting patients at high risk who do NOT have dysplasia Can OB detect patients at risk

21. Detecting �Field Change� Effect Animal model of colon cancer Aberrant crypt foci is the first visible change ESS detects �fingerprint� of microarchitectural abnormalities BEFORE aberrant crypt foci visible ( Roy et al, Gastroenterology (2004); 126: 1071) Human Colorectal Cancer Risk Stratification 37 patients Colonoscopy in those with/without previous adenomas Similar findings to animal models ( Roy et al, DDW 2005)

22. The Questions How do we prevent death from esophageal adenocarcinoma? How do we detect patients at risk? How do we best treat patients?

23. Treatment for HGD in Barrett�s Oesophagus Oesophagectomy Morbidity � 40% Mortality � 5% Elderly patients Need for minimally invasive therapy Aim Show the problems of conventional treatment Quote number not fit for surgery Standard treatment of total oesophagectomy High morbidity and significant mortality High risk to the patient of prolonged stay and of death Its still needed, but �Hugh Barr�s quote Need for minimally invasive treatment QUOTE on another slide? With figure of oesophagectomyAim Show the problems of conventional treatment Quote number not fit for surgery Standard treatment of total oesophagectomy High morbidity and significant mortality High risk to the patient of prolonged stay and of death Its still needed, but �Hugh Barr�s quote Need for minimally invasive treatment QUOTE on another slide? With figure of oesophagectomy

24. Mucosal Ablation Thermal (hot/cold) Laser MPEC Cryotherapy Photochemical (PDT)

25. The Ideal of Mucosal Ablation Selective mucosal destruction Ambulatory therapy No side effects Strictures Photosensitivity Acute Hypotension Buried glands

28. PDT Results: Barrett�s Esophagus

29. Results (ALA) From October 1999 75 patients treated (most after 2002) All had high grade dysplasia (V4) 3 studies: High dose ALA (60mg/kg) Light dose ranging (low, medium, high light dose) RCT ALA 30 mg/kg with red v green light RCT ALA 60 mg/kg with red v green light UpdateUpdate

30. ALA 60 mg/kg (high dose):Red Light at various doses

31. ALA 30 mg/kg (low dose):Red v Green Light

32. Rescue with high dose ALAand various light doses

33. ALA PDT 75 patients treated Best regime: 80% clearance HGD at 2 years Toxicity (all at 60mg/kg) 4 patients: severe hypotension (prevented by rehydration and avoiding psychotropic drugs) 3 patients: aspiration pneumonia 8 patients: transient fever 2 patients: asymptomatic jaundice, cleared in 5 days

34. ALA PDT Looks promising but there are toxicity issues

35. Foscan Mucosal Selectivity Explain the box-plot Interquartile range MedianExplain the box-plot Interquartile range Median

36. Verteporfin photosensitiser(2mg/kg, activated at 15 minutes) Ivc injection, full bladder!Ivc injection, full bladder!

37. Duodenal PDT Histology 10 J to pancreas (therefore adjacent damage). Slide on left shows loop of duodenum with complete necrosis of duodenal mucosa. Slides on right ( low and high power)10 J to pancreas (therefore adjacent damage). Slide on left shows loop of duodenum with complete necrosis of duodenal mucosa. Slides on right ( low and high power)

38. Duodenal collagen resistant to damage

39. The Ideal of Mucosal Ablation Selective mucosal destruction Ambulatory therapy No side effects Strictures Photosensitivity Acute Hypotension Buried glands

40. Conclusions Optical methods might be developed to detect patients at highest risk New PDT approaches to treat HGD in BE Can optical methods be used to assess the outcome of PDT?