Bono Vince Malum (Overcome Evil with Good )

LACTIC DEHYDROGENASE AND BETA-GLUCURONIDASE IN THE HUMAN STOMACH WITH SPECIAL REFERENCE TO GASTRIC CANCER

Submitted for the degree of Doctor of Medicine, May 1988

Peter John Finch MBBS(Honours) MRCP(UK)

St Thomas's Hospital Medical School

University of London

ABSTRACT

A complete copy is available for download as a PDF file (c) 2010 Dr Peter Finch

The factors which affect the levels of the enzymes lactic dehydrogenase (LDH) the m-LDH subunit and beta-glucuronidase in gastric tissue homogenates and in a gastric wash sample obtained at endoscopy, were investigated. The potential of using the measurement of these enzymes in a gastric wash sample as a screening test for gastric cancer was also evaluated in patients undergoing routine endoscopy.

Studies of tissue homogenates from resected stomach specimens showed increases in beta-glucuronidase in gastritis, intestinal metaplasia and carcinoma, an increase in LDH in carcinoma, and an increased m-LDH subunit fraction in gastritis, carcinoma and intestinal metaplasia, particularly the sulphomucin containing variant. Correlations were found between the degree of chronic inflammatory infiltrate and LDH and the m-LDH subunit fraction, and also between intestinal metaplasia and the m-LDH subunit fraction. A similar trend was also found in gastric wash samples obtained at endoscopy: increased LDH and beta- glucuronidase was found in endoscopic gastritis, gastric ulcer, histological gastritis and intestinal metaplasia. Marked increases in these enzymes were found in gastric cancer. No significant differences in m-LDH subunit fraction were found amongst the gastric wash samples.

An index combining LDH and beta-glucuronidase level in a gastric wash sample was evaluated as a screening test for gastric cancer, and gave a sensitivity of 87.5%. The specificity was 81.2% but 87.3% of the false positives had endoscopic evidence of inflammation, and 96.1% of the false positives who were biopsied had atrophic gastritis, either alone or with intestinal metaplasia. Follow-up revealed two cases of early gastric cancer amongst the "false positives". There was a higher prevalence of severe dysplasia and sulphomucin containing intestinal metaplasia amongst the false positives. This test appears to be a useful screening test for gastric cancer, and in particular, it may identify a group who are at increased risk of developing gastric cancer in the future.