Clinical implications of gastrointestinal epithelial dysplasia in surveillance programmes

• Main Author: Lim, Chee Hooi
• Published: University of Leeds 2007
• Subjects: 616.3
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.485308

This thesis has focused on the clinical implication of low-grade dysplasia (LGD) identified in Barrett's oesophagus and ulcerative colitis (UC) surveillance programmes. I have completed two retrospective cohort studies to determine the outcome of LGD at least 8 to 10 years after its diagnosis and carried out a histological review of the original diagnoses of LGD. There were 40 LGD in the 160 cohort of UC patients who entered surveillance programme and 34 LGD in 357 cohorts of Barrett's oesophagus patients. Further studies were undertaken to evaluate new technologies and methods to improve the detection of dysplasia. Results: After 10 years HGD or colorectal cancer developed in 3/29 LGD (10%) and in 4/97 controls (4.0%). Kaplan-Meier analysis from 1991 to death or colectomy did not show a statistically significant difference between the two groups. Histopathological review demonstrated the unreliability of LGD diagnosis in chronic UC. Agreement between pathologists was uniformly poor. The Barrett's oesophagus study showed that after 8 years, high-grade dysplasia (HGD) or oesophageal adenocarcinoma developed in 9/34 LGD (27%) and in 16/322 controls (5%). Cox's proportional hazards model showed a significantly increased risk for the LGD group to progress to HGD or cancer if death was treated as loss to follow-up. None of the molecular markers for colorectal cancer showed any difference in protein expression for cancer, dysplasia or non-neoplastic mucosa except p16. There was a trend of over-expression of p16 protein from 0% in controls to 47% (8/17) in UC related cancer. Thirty patients completed the cross-over study for chromoendoscopy in Barrett's oesophagus. Overall, dysplasia was identified in 17 of 18 patients by random biopsies and in 9 of 18 by methylene blue directed biopsies. Conclusion: A diagnosis of low grade dysplasia in UC is not sufficiently reliable to justify prophylactic colectomy. Conservative management of established LGD cases should not be ruled out. Patients diagnosed with LGD during surveillance of Barrett's oesophagus on the other hand are at a considerably increased risk of progression to oesophageal cancer. Over-expression of p16 protein in UC may suggest neoplastic change.