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.
|Datta, Somenath; Sherva, Richard M; De La Cruz, Mart et al. (2018) Single Nucleotide Polymorphism Facilitated Down-Regulation of the Cohesin Stromal Antigen-1: Implications for Colorectal Cancer Racial Disparities. Neoplasia 20:289-294|
|Gladstein, Scott; Damania, Dhwanil; Almassalha, Luay M et al. (2018) Correlating colorectal cancer risk with field carcinogenesis progression using partial wave spectroscopic microscopy. Cancer Med 7:2109-2120|
|Liu, Rongrong; Spicer, Graham; Chen, Siyu et al. (2017) Theoretical model for optical oximetry at the capillary level: exploring hemoglobin oxygen saturation through backscattering of single red blood cells. J Biomed Opt 22:25002|
|Bauer, Greta M; Stypula-Cyrus, Yolanda; Subramanian, Hariharan et al. (2017) The transformation of the nuclear nanoarchitecture in human field carcinogenesis. Future Sci OA 3:FSO206|
|Chowdhury, Sanjib; Roy, Hemant K (2017) The genetics and molecular biology of colonic neoplasia: practical implications for the clinician. Curr Opin Gastroenterol 33:47-52|
|Cruz, Mart Dela; Ledbetter, Sarah; Chowdhury, Sanjib et al. (2017) Metabolic reprogramming of the premalignant colonic mucosa is an early event in carcinogenesis. Oncotarget 8:20543-20557|
|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|
|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|
|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|
|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|
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