Screening colonoscopy in average-risk subjects demonstrated a considerable prevalence of CR neoplasia and proximal lesions beyond the reach of sigmoidoscopy. The morbidity rate was negligible. Primary screening colonoscopy should be considered in health programs for the average-risk population, beginning at the age of 50 yr. The significantly high rate of advanced and proximal neoplasia in the elderly, encourages the inclusion of healthy subjects aged 76-80 yr in future prospective studies.

Neoplastic progression in Barrett's esophagus is a multistep process in which the metaplastic columnar epithelium sequentially evolves through a metaplasia-dysplasiacarcinoma sequence. The expression and DNA copy number of key cell cycle regulatory genes in paired normal and Barrett's esophagus samples was evaluated. Protein levels were evaluated in 60 formalin-®xed, para n-embedded human tissues by immunohistochemistry. DNA copy number from 20 fresh tissue pairs was analysed by Southern blot analysis. All normal mucosal samples expressed the p27 kip1 protein, but did not display appreciable nuclear staining for p16 kip4 , p21 cip1 or cyclins D1 and E. Barrett's metaplastic specimens displayed increased expression levels of p16 kip4 (74%), p21 cip1 (89%) and cyclins D1 (43%) and E (37%). p27 protein was absent in three cases. There was a signi®cant correlation between the expression of p16 kip4 and cyclin E, and p21 cip1 and p27 kip4 with cyclin D1. DNA analysis did not reveal any ampli®cation or deletion of these genes. Acid suppression, however, was associated with signi®cantly lower expression levels of key cell cycle proteins. Increased expression of key cell cycle regulatory genes appears to occur early in the neoplastic progression associated with Barrett's esophagus. Treatment with proton pump inhibitors appears to alter this increased expression. Oncogene (2001) 20, 7987 ± 7991.

Screening colonoscopy in asymptomatic, average-risk individuals is mandatory, as noteworthy numbers of advanced colorectal neoplasias have been detected in all age groups, especially in those aged > 75. Most importantly, many of the detected lesions were proximal and would not be revealed by sigmoidoscopy alone.

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