Materials and Methods

• High risk subjects over 45 years old
  • smokers or former smokers with a smoking history of > 29 pack years
  • previously completely resected stage 1 non-small cell lung cancer
  • stage T1/T0 N0 squamous cancer of head & neck > 6 months disease free
• Written informed consent was obtained from each patient
• Treatment
  • Sulindac 150 mg orally BID versus placebo for 6 months or
  • Sialor (anetholtrithione) 25 mg orally TID for 6 months
• Examination
  • A conventional white light bronchoscopy followed by fluorescence bronchoscopy (LIFE, Xillix) before and 6 months after treatment
  • All areas suspicious for dysplasia or cancer under either examination were biopsied
• Serial sections were obtained from the biopsies
• Sections numbered one and six were H&E stained and coverslipped
• All H&E stained biopsied sections were systematically reviewed by at least two pathologists and all lesions classified into one of eight groups:
  • normal, reserve cell hyperplasia, metaplasia, mild dysplasia
  • moderate dysplasia, severe dysplasia, carcinoma in situ
  • microinvasive, invasive carcinoma
• The area in the H&E stained biopsy used to classify the sample was photographically recorded
• The immediately adjacent section was quantitatively stained
• Exactly the same area used to assign the pathological classification was quantitatively analyzed (Images of all the non-overlapping cell nuclei collected)
• Additionally, ~30 leukocytes were collected to normalize the images for sample to sample variations in staining intensity
• For each nuclei 126 features were calculated

Figure 8: Morphometric Index: Before and After Sulindac Chemoprevention [View Image]

Figure 9: Morphometric Index: Before and After Chemoprevention (Placebo) [View Image]

Figure 10: Morphometric Index: Before and After Sialor Chemoprevention [View Image]