UNIVERSITY OF CALGARY Non-medical reasons for colectomy among ulcerative colitis patients by

UNIVERSITY OF CALGARY
Non-medical reasons for colectomy among ulcerative colitis patients
by
María Eugenia Negrón
A THESIS
SUBMITTED TO THE FACULTY OF GRADUATE STUDIES
IN PARTIAL FULFILMENT OF THE REQUIREMENTS FOR THE
DEGREE OF DOCTOR OF PHILOSOPHY
VETERINARY MEDICAL SCIENCES GRADUATE PROGRAM
CALGARY, ALBERTA
July, 2014
© María E. Negrón
2014

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Abstract
Approximately 16% of ulcerative colitis (UC) patients will have a colectomy
within 10 years of their diagnosis of UC. Due to the high morbidity and mortality
associated with colectomy procedures, clinicians and patients strive to avoid surgery. The
decline of colectomy rates over the last 6 decades has been mainly attributed to advances
in medical management of UC. Clostridium difficile infection and colorectal neoplasia
have also been associated with driving the risk of colectomy. This dissertation focuses on
describing the effect of C. difficile and colorectal neoplasia on the risk of colectomy for
UC patients. Chapters 2 and 3 establish the cumulative risk of acquiring C. difficile
infection after the diagnosis of UC and demonstrated that C. difficile infections increase
the short- and long-term risk of colectomy. Further, both Chapters 2 and 3 demonstrate
that C. difficile infections increased the risk of postoperative complications following
colectomy for UC. Chapter 4 demonstrate that the incidence of colectomy for colorectal
dysplasia and cancer has remained stable over time, and showed that the observed
decrease in colectomy rates is most likely due to a decrease in colectomies from
medically refractory disease. Finally, Chapter 5 determined the cost-effectiveness of
different surveillance colonoscopy intervals for colorectal dysplasia among a subgroup of
inflammatory bowel disease (IBD) patients with a higher risk of developing colorectal
dysplasia and cancer; i.e., patients with IBD and primary sclerosing cholangitis (PSC).

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Preface
This dissertation consists of four manuscripts – two of which have been accepted
for publication, and two are ready for submission. For all four manuscripts, the first
author was involved with study concept and design, acquisition of data, analysis and
interpretation of data, drafting of the manuscript, and critical revision. This was done
under the guidance of the supervisor and co-supervisor. All authors provided critical
reviews of the manuscripts and contributed intellectual content. After receiving written
permission from the publishers and co-authors, all four manuscripts were reproduced in
their entirety as chapters in this dissertation.
Manuscript I) Negrón ME, Barkema HW, Rioux K, De Buck J, Checkley S, Proulx MC,
Frolkis A, Beck PL, Dieleman L, Panaccione R, Ghosh S, Kaplan GG. Clostridium
difficile infection worsens prognosis of ulcerative colitis. Accepted: Canadian Journal of
Gastroenterology and Hepatology.
Manuscript II) Negrón ME, Barkema HW, Kaplan GG. Clostridium difficile infection
diagnosed early in ulcerative colitis patients impacts disease related outcomes: A
population-based inception cohort study. Will be submitted to: Gut.
Manuscript III) Negrón ME, Barkema HW, Kaplan GG. Changes in the annual incidence
of colectomy for colorectal neoplasia among UC patients: A population-base study. Will
be submitted to Clinical Gastroenterology and Hepatology

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Manuscript IV) Negrón ME, Kaplan GG, Barkema HW, Eksteen B, Clement F, Manns
BJ, Coward S, Panaccione R, Ghosh S, Heitman SJ. Colorectal cancer surveillance in
patients with inflammatory bowel disease and primary sclerosing cholangitis: An
economic evaluation. Accepted: Inflammatory Bowel Disease.

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Acknowledgements
I would like to express my most sincere gratitude to my supervisor and co-
supervisor, Drs. Herman W. Barkema and Gilaad G. Kaplan. Herman and Gil, I admire
both of you as my mentors, colleagues and as a people. Thank you for your patience, for
believing in me and guiding me during these last 4 years. You have no idea how much I
learned from both of you! I also want to thank my committee members: Drs. Sylvia
Checkley, Jeroen De Buck, Bertus Eksteen and Kevin Rioux for their guidance and
support. Additionally, I want to thank Drs. Fiona Clement and Steven Heitman who
introduced me to the world of health economics. I hope I make you both proud! I would
like to show my deepest appreciation to Karin Orsel, who has been a friend and a mentor
during these last 4 years. Thank you for being available to chat and for giving guidance
when I needed it. I would like to acknowledge my lab members, Alex, Ellen and
Stephanie for all those stimulating discussions and for all the fun we had during these last
few years. In particular, Alex, I admire your wisdom and your attitude towards life.
Thank you for taking time to brainstorm with me.
To the amazing people I get to call my friends in Calgary. You guys are the
epitome of what a family away from home means. Most importantly, Andrew, your care,
support and confidence in me were all that kept me going at times during these last few
months. Thank you, love.
I would like to acknowledge the DIMR departments for providing the data for the
patients with ulcerative colitis living in the Calgary Health Zone, and Calgary Laboratory
Services for providing the Clostridium difficile test results. Finally, I would like to
recognize the financial assistance of the University of Calgary (Teaching Assistantships,