Browsing by Author "Hilsden, Robert"

Now showing 1 - 11 of 11
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    A quantitative multimodal metabolomic assay for colorectal cancer
    (2018-01-04) Farshidfar, Farshad; Kopciuk, Karen A; Hilsden, Robert; McGregor, S. E; Mazurak, Vera C; Buie, W. D; MacLean, Anthony; Vogel, Hans J; Bathe, Oliver F
    Abstract Background Early diagnosis of colorectal cancer (CRC) simplifies treatment and improves treatment outcomes. We previously described a diagnostic metabolomic biomarker derived from semi-quantitative gas chromatography-mass spectrometry. Our objective was to determine whether a quantitative assay of additional metabolomic features, including parts of the lipidome could enhance diagnostic power; and whether there was an advantage to deriving a combined diagnostic signature with a broader metabolomic representation. Methods The well-characterized Biocrates P150 kit was used to quantify 163 metabolites in patients with CRC (N = 62), adenoma (N = 31), and age- and gender-matched disease-free controls (N = 81). Metabolites included in the analysis included phosphatidylcholines, sphingomyelins, acylcarnitines, and amino acids. Using a training set of 32 CRC and 21 disease-free controls, a multivariate metabolomic orthogonal partial least squares (OPLS) classifier was developed. An independent set of 28 CRC and 20 matched healthy controls was used for validation. Features characterizing 31 colorectal adenomas from their healthy matched controls were also explored, and a multivariate OPLS classifier for colorectal adenoma could be proposed. Results The metabolomic profile that distinguished CRC from controls consisted of 48 metabolites (R2Y = 0.83, Q2Y = 0.75, CV-ANOVA p-value < 0.00001). In this quantitative assay, the coefficient of variance for each metabolite was <10%, and this dramatically enhanced the separation of these groups. Independent validation resulted in AUROC of 0.98 (95% CI, 0.93–1.00) and sensitivity and specificity of 93% and 95%. Similarly, we were able to distinguish adenoma from controls (R2Y = 0.30, Q2Y = 0.20, CV-ANOVA p-value = 0.01; internal AUROC = 0.82 (95% CI, 0.72–0.93)). When combined with the previously generated GC-MS signatures for CRC and adenoma, the candidate biomarker performance improved slightly. Conclusion The diagnostic power for metabolomic tests for colorectal neoplasia can be improved by utilizing a multimodal approach and combining metabolites from diverse chemical classes. In addition, quantification of metabolites enhances separation of disease-specific metabolomic profiles. Our future efforts will be focused on developing a quantitative assay for the metabolites comprising the optimal diagnostic biomarker.
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    Economic evaluation of colerectal cancer screening for average risk individuals
    (2012) Heitman, Steven James; Manns, Braden; Hilsden, Robert
    Background: Colorectal cancer (CRC) is a common deadly cancer. Screening for CRC saves lives and is cost-effective, but it is unclear if one or more of the screening options are preferred. Methods: A Markov model was developed and validated and then used to conduct an economic evaluation of CRC screening for average risk individuals. All current CRC screening modalities and up to date CRC treatment costs were considered. A systematic review and meta-analysis of CRC and adenomatous polyp prevalence was also performed to inform the model. Results: The prevalence of non-advanced adenomas, advanced adenomas and CRC in 50-64 and 65-75 year olds was 17.1%, 3.8% and 0.1% and 17.3%, 8.2% and 0.7%, respectively. In the base case analysis CRC screening with annual FIT reduced the risk of CRC and CRC-related deaths and was associated with lower health care costs compared to no screening and the other screening options. Conclusion: Health policy decision makers should prioritize funding for CRC screening using FIT.
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    Immunogenicity and Safety of Influenza Vaccination in Children with Inflammatory Bowel Disease
    (2010) deBruyn, Jennifer Carole Cheung; Hilsden, Robert
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    Incidence and Risk Factors Associated with Endoscopic Retrograde Cholangiopancreatography-Related Bleeding
    (2022-06) Bishay, Kirles; Forbes, Nauzer; Heitman, Steven; Hilsden, Robert; Bridges, Ron
    Endoscopic retrograde cholangiopancreatography (ERCP) is the cornerstone of therapy for an array of pancreaticobiliary disorders. While highly effective, ERCP-related bleeding is a possible adverse event with an estimated incidence of 2% which can lead to substantial morbidity and mortality. This thesis reports the results of two studies performed with the aim of evaluating the incidence of and risk factors associated with the development of ERCP-related bleeding. Our meta-analysis of observational and randomized trials showed that while the contemporary incidence of bleeding is in keeping with historical estimates, bleeding risk varies considerably within several important patient- and procedure-related subgroups. We then demonstrated via a multicenter prospective cohort study the risk factors associated with both intraprocedural and clinically significant delayed ERCP-related bleeding. We demonstrated that patient sex, kidney disease, papilla morphology, antithrombotic use and procedural techniques contribute to bleeding risk after adjusting for important covariates. Together, these findings demonstrate that bleeding risk in ERCP varies substantially depending on several factors. Clinicians performing ERCP can use our findings to accurately assess bleeding risk permitting tailored risk mitigation management amongst individuals at high risk and to communicate accurate bleeding risk estimates to patients for conferral of informed consent.
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    Metabolomic Biomarkers for Colorectal Cancer
    (2016) Farshidfar, Farshad; Bathe, Oliver F.; Vogel, Hans J; Kopciuk, Karen A; Hilsden, Robert; Buie, W. Donald
    Colorectal cancer (CRC) is the second most common cancer in the North America. It is also a huge burden for society. Remarkable efforts have been and are being made to improve CRC diagnosis, to enhance the effectiveness of treatments, and to eventually improve the outcome of these patients. Metabolomic profiling, as a method for describing metabolic state and alterations in the molecular constituents and capable of yielding unique and invaluable information about tumor biology, has been employed. Using a range of spectroscopy and mass spectrometry techniques, we have sought to characterize the changes in the serum metabolome that appear as a result of malignant and pre-malignant lesions in the colon and rectum. In Chapter 2, Application of gas chromatography-mass spectrometry (GC-MS) and nuclear magnetic resonance (NMR) spectroscopy for staging CRC is described. Chapter 3 describes a larger study of 320 CRC and 31 colorectal adenoma cases as well as their matching controls by GC-MS, which led to the identification of validated metabolomic signature for identification of CRC and a proposed signature for identification of colorectal adenoma. In chapter 4, an effort for quantitative profiling of 62 CRC cases and 31 colorectal adenomas and their matching controls by tandem mass spectrometry is illustrated, and a validated quantitative signature for diagnosis of CRC is reported. Chapter 5 is dedicated to studying the prognostic value of metabolomic profiling in colorectal liver metastatic patients, and a novel workflow for estimation of recurrence risk using high-dimensional data is proposed. Challenges and pitfalls confronted in different steps of the project were addressed when possible by the use of available methods. Where no reliable method was available, we made an effort to develop one. This thesis, therefore, is focused on the metabolomic characterization of CRC and the adaptation of this knowledge for the development of clinically valuable biomarkers.
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    Post-colorectal cancer screening: knowledge and understanding
    (2007) Walker, Robin L.; Hilsden, Robert; McGregor, S. Elizabeth
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    Practice Patterns, Predictors of Use and Clinical Efficacy of Endoscopic Clips for Prevention of Delayed Post-polypectomy Bleeding
    (2017-12-12) Forbes, Nauzer; Heitman, Steven; Hilsden, Robert; Kaplan, Gilaad; James, Matthew
    Colonoscopy reduces colorectal cancer through the removal of pre-cancerous polyps, which exposes patients to potential adverse events. Endoscopic clips are used by practitioners to prevent delayed post-polypectomy bleeding. This thesis reports the results of two studies performed with the aim of evaluating the practice patterns and clinical efficacy of prophylactic clipping during polypectomy. A meta-analysis of randomized trials showed that prophylactic clipping is not efficacious in preventing delayed bleeding during routine polypectomy, especially among polyps < 10 mm. A large retrospective cohort study then described clinical parameters associated with clip usage. We demonstrated that use of clips increased over time in a high-volume outpatient endoscopy unit. Furthermore, a high degree of variability in clipping patterns existed between endoscopists, including among polyps < 10 mm, where no efficacy exists. Taken together, these results reveal an urgent need for effective knowledge translation to eliminate this ineffective and costly practice during routine polypectomy.