Studies of Established Forms of Therapy for Peptic Ulcer on the Development and Growth of Colorectal Cancer: The Influence of Previous Peptic Ulcer Surgery and Omeprazole

Duncan, James Robert (1998) Studies of Established Forms of Therapy for Peptic Ulcer on the Development and Growth of Colorectal Cancer: The Influence of Previous Peptic Ulcer Surgery and Omeprazole. MD thesis, University of Glasgow.

Abstract

Colorectal cancer and peptic ulcer are two of the most commonly encountered diseases in present day medical practice. The work which is reported in this thesis links these two very different diseases, by investigation of the effects of various forms of treatment for one, on the the incidence and behaviour of the other, both in a deleterious and potentially beneficial fashion to the patient. Many reports have suggested that patients who have previously undergone definitive surgery for peptic ulcer are left with the legacy of an increased propensity for developing malignant disease approximately 15 to 20 years later. Gastric cancer has regularly been identified as being one such cancer. To a much lesser extent, colorectal cancer has also been reported as occurring with undue frequency in a number of patient series studied. With few exceptions, the majority of patients studied have previously undergone partial gastric resection as opposed to vagotomy. The latter procedure, although reducing gastric acid output to a similar degree as partial gastrectomy, differs markedly from it by virtue of the chronic elevation of circulating gastrin levels, secreted from the non-resected stomach, which occurs post-operatively. This may be an important factor in the development of colorectal cancer, as a significant body of evidence suggests that gastrin is trophic for a proportion of such neoplasms. There may therefore be implications for the prolonged use of the latest pharmaceutical agents used against acid-peptic disorders, namely the proton-pump inhibitors of which omeprazole is the original. Similar to vagotomy, these drugs induce a chronic elevation of circulating gastrin, secondary to the reduction in acid output. In view of this association, one of the main purposes of the work which follows was to study the cancer incidence, in particular that of colorectal cancer, in a group of patients who had undergone surgery for peptic ulcer disease, the majority of whom had vagotomy as opposed to antrectomy. Somewhat conversely, the remainder of the work in this thesis concentrates on investigating a possible inhibitory action of omeprazole on colorectal tumour growth, despite the chronic hypergastrinaemia which it produces. This is in response to two recent reports which suggest that the drug may have such an effect on these tumours, under experimental conditions. Hence, it seems appropriate to open this account with a brief overview of the diseases under scrutiny; namely colorectal cancer and peptic ulcer; and to continue by explaining the rationale behind both surgical and medical treatment for the latter. This should give the reader a clear understanding of the pathophysiological changes that occur in response to such treatment, and why they may have potentially deleterious effects, or otherwise, elsewhere in the gastrointestinal tract. In the latter part of the introductory chapter, the evidence, both for and against the phenomena under investigation, will be reviewed, and this will illustrate the stimulus to the work carried out for this thesis.

• Item Type: Thesis (MD)
• Qualification Level: Doctoral
• Additional Information: Adviser: David George
• Keywords: Medicine
• Date of Award: 1998
• Depositing User: Enlighten Team
• Unique ID: glathesis:1998-74868
• Copyright: Copyright of this thesis is held by the author.
• Date Deposited: 27 Sep 2019 15:45
• Last Modified: 27 Sep 2019 15:45
• URI: https://theses.gla.ac.uk/id/eprint/74868