Scientific Abstract
Proposal No. IBD-0015R
Principal Investigator: Michael B. Wallace, M.D., MPH
Applicant Organization: Medical University of South Carolina (Charleston, U.S.A.)
Project Title: Evaluation of spectroscopy for the detection of dysplasia in Interleukin-10-deficient mice with enterocolitis – a pilot study
Period of Award: December 1, 2002 - August 26, 2003
Aim: To determine the ability of Trimodal (intrinsic fluorescence, diffusion reflectance, light scattering) spectroscopy (TMS) for the detection of dysplasia in Interleukin-10-deficient mice with enterocolitis.
Background: There is strong evidence that endoscopic screening and surveillance can prevent some gastrointestinal cancers when endoscopically visible dysplastic lesions (e.g., polyps) are present. Screening and surveillance of other forms of dysplasia as Barrett’s esophagus and inflammatory bowel disease may also be helpful, but are limited by many factors such as nonvisible (flat) dysplasia, the need for random biopsy, and sampling error. Endoscopic spectral methods have the potential to overcome many of the limitations by rapidly and safely evaluating wide regions of tissue for dysplasia without required excision of the tissue. The Laser Biomedical Research Center at the Massachusetts Institute of Technology (MIT) and the Digestive Disease Center at the Medical University of South Carolina (MUSC) located in Charleston have been extensively involved in the development and validation of spectroscopic techniques for detecting gastrointestinal dysplasia.
Patients with inflammatory bowel disease (IBD), either ulcerative colitis (UC) or Crohn’s disease (CD), are at increased risk for the development of gastrointestinal carcinoma. Despite some controversy about the care of these patients, surveillance is widely practiced and recommended. Dysplastic areas are often difficult to recognize by endoscopy. They may appear as flat or only slightly elevated above the level of the mucosa. This is why it is recommended to take frequent blind biopsies.
Developing dysplasia in longstanding IBD is not a common event. When there is evidence of dysplasia, most of the time a colectomy is performed. With regard to determining the role of spectroscopy in this setting, it would be very difficult and time consuming to identify enough patients with dysplastic changes in their colon to test spectroscopy in them. Therefore, we planned a pilot study with an animal model to get some preliminary data of the TMS and to justify a larger and longer-term study in humans. There are several reports in the literature indicating that IL-10-deficient mice develop enterocolitis and subsequent dysplasia in a great number. With the help of this animal model and a sufficient number of animals with dysplasia, we can determine the ability of spectroscopy to reliably detect dysplasia in this setting.
Methods: We will evaluate in vivo and ex vivo specimens from the IL-10-deficient mice with known enterocolitis and dysplasia. Four days prior to the surgery and spectroscopic measuring, we will treat the animals with a subcutaneous injection of a depot steroid to reduce colonic inflammation and to make it easier to interpret the microscopic changes of dysplasia. The surgeon will open the entire colon with ongoing blood supply of the intestine under general anesthesia. Spectra and corresponding standard biopsies will be collected from the lanced colon. Dysplasia will be categorized by consensus diagnosis of two GI pathologists. The spectral signal will be analyzed at MIT. As control data, we will use biopsies and spectral data from non-dysplastic sites. Assuming a sensitivity of at least 80% with a significance level of 0,05 and a statistical power of 0,8, we need at least 68 dysplastic biopsies. We estimate to find a maximum of four dysplastic sites per animal, so there is a need for 17-20 IL-10-deficient mice.
Foundation criteria: Although this project is in the early stages of exploration, we have extensive experience with developing TMS for the detection of similar forms of dysplasia in Barrett’s esophagus and colon adenoma. The TMS is a very new technology and never used in the colon for ulcerative colitis surveillance. We believe that spectroscopy will improve the clinical care and effectiveness of surveillance of longstanding IBD by reducing sampling errors of random biopsy, guiding biopsies to appropriate locations, and avoiding unnecessary biopsies. This increased accuracy could also lead to a reduction in the frequency needed for effective surveillance colonoscopies.