Colorectal cancer (CRC) remains the second leading cause of cancer death among Americans largely because colonoscopic screening for all the >100 million Americans over age 50 is unfeasible from both a patient (non-compliance) and societal (inadequate endoscopic capacity/funding) perspective. This is juxtaposed by the fact that average risk screening and surveillance (repeat colonoscopy for a previous adenoma history) is remarkably unproductive with advanced adenoma yields of only 6-10%. Thus, pre- colonoscopic risk-stratification development is of crucial. We have developed a suite of novel light-scattering technologies to sensitively detect microvascular (MVS) and micro- architectural (via low-coherence enhanced backscattering, LEBS) manifestations of field carcinogenesis. Published results from >500 patients indicated that interrogation of the endoscopically normal rectum for MVS or LEBS reliably predicted advanced adenomas elsewhere in the colon (AUROC 0.88 and 0.89, respectively). We have recently achieved a technological breakthrough that allows, for the first time, concurrent measurement of MVS/LEBS markers via a single fiber-optic probe. Importantly, on a pilot dataset, the diagnostic performance was synergistic improving AUROC by ~7-10% thereby enabling detection of all adenomas >mm. Moreover, the rectal fiber-optic probe can be employed without a bowel purge. This proposal will test the hypothesis that combined rectal MVS/LEBS markers analysis will enable accurate risk stratification. We will first identify the precise location of the MVS/LEBS alterations and optimize the fiber- optic probe penetration depth by performing biological/imaging studies on ex vivo tissue and in vivo. Secondly, we will evaluate the ability of this optimized rectal fiber-optic probe to predict advanced adenomas in average risk patients using a training (n=500) and testing set (n=750) in both prepped and unprepped patients. Finally, we will validate this approach on patients (n=400) undergoing surveillance (previous neoplasia). These studies will confirm that MVS/LEBS fiber-optic probe rectal examination provides sensitive, minimally-intrusive risk analysis technique thereby heralding the era of personalized medicine for CRC population screening.
CRC impacts 150,000 Americans per year despite being eminently preventable by colonoscopy. However, colonoscopy for the entire population is impractical (not enough funding or endoscopists) and inefficient (most screening colonoscopies are negative). Our approach is to develop a minimally intrusive, highly accurate pre-screen that would allow tailoring timing/intensity of screening and surveillance.
|Wali, Ramesh K; Momi, Navneet; Dela Cruz, Mart et al. (2016) Higher Order Chromatin Modulator Cohesin SA1 Is an Early Biomarker for Colon Carcinogenesis: Race-Specific Implications. Cancer Prev Res (Phila) 9:844-854|
|Calderwood, Audrey H; Lasser, Karen E; Roy, Hemant K (2016) Colon adenoma features and their impact on risk of future advanced adenomas and colorectal cancer. World J Gastrointest Oncol 8:826-834|
|Roy, Hemant K; Brendler, Charles B; Subramanian, Hariharan et al. (2015) Nanocytological field carcinogenesis detection to mitigate overdiagnosis of prostate cancer: a proof of concept study. PLoS One 10:e0115999|
|Mutyal, Nikhil N; Radosevich, Andrew J; Bajaj, Shailesh et al. (2015) In vivo risk analysis of pancreatic cancer through optical characterization of duodenal mucosa. Pancreas 44:735-41|
|Radosevich, Andrew J; Mutyal, Nikhil N; Eshein, Adam et al. (2015) Rectal Optical Markers for In Vivo Risk Stratification of Premalignant Colorectal Lesions. Clin Cancer Res 21:4347-55|
|Cruz, Mart Dela; Wali, Ramesh K; Bianchi, Laura K et al. (2014) Colonic mucosal fatty acid synthase as an early biomarker for colorectal neoplasia: modulation by obesity and gender. Cancer Epidemiol Biomarkers Prev 23:2413-21|
|Wali, Ramesh K; Hensing, Thomas A; Ray, Daniel W et al. (2014) Buccal microRNA dysregulation in lung field carcinogenesis: gender-specific implications. Int J Oncol 45:1209-15|
|Yi, Ji; Radosevich, Andrew J; Stypula-Cyrus, Yolanda et al. (2014) Spatially resolved optical and ultrastructural properties of colorectal and pancreatic field carcinogenesis observed by inverse spectroscopic optical coherence tomography. J Biomed Opt 19:36013|
|Stypula-Cyrus, Yolanda; Mutyal, Nikhil N; Dela Cruz, Mart et al. (2014) End-binding protein 1 (EB1) up-regulation is an early event in colorectal carcinogenesis. FEBS Lett 588:829-35|
|Patel, Mihir; Gomes, Andrew; Ruderman, Sarah et al. (2014) Polarization gating spectroscopy of normal-appearing duodenal mucosa to detect pancreatic cancer. Gastrointest Endosc 80:786-93.e1-2|
Showing the most recent 10 out of 26 publications