Journal of biomedical optics 2013 Sep
Authors: Radosevich AJ, Mutyal NN, Yi J, Stypula-Cyrus Y, Rogers JD, Goldberg MJ, Bianchi LK, Bajaj S, Roy HK, Backman V,
Optical characterization of biological tissue in field carcinogenesis offers a method with which to study the mechanisms behind early cancer development and the potential to perform clinical diagnosis. Previously, low-coherence enhanced backscattering spectroscopy (LEBS) has demonstrated the ability to discriminate between normal and diseased organs based on measurements of histologically normal-appearing tissue in the field of colorectal (CRC) and pancreatic (PC) cancers. Here, we implement the more comprehensive enhanced backscattering (EBS) spectroscopy to better understand the structural and optical changes which lead to the previous findings. EBS provides high-resolution measurement of the spatial reflectance profile P(rs) between 30 microns and 2.7 mm, where information about nanoscale mass density fluctuations in the mucosa can be quantified. A demonstration of the length-scales at which P(rs) is optimally altered in CRC and PC field carcinogenesis is given and subsequently these changes are related to the tissue's structural composition. Three main conclusions are made. First, the most significant changes in P(rs) occur at short length-scales corresponding to the superficial mucosal layer. Second, these changes are predominantly attributable to a reduction in the presence of subdiffractional structures. Third, similar trends are seen for both cancer types, suggesting a common progression of structural alterations in each.
PMID: 24008865 [PubMed - as supplied by publisher]
Cancer research 2012 Jun 1
Authors: Damania D, Roy HK, Subramanian H, Weinberg DS, Rex DK, Goldberg MJ, Muldoon J, Cherkezyan L, Zhu Y, Bianchi LK, Shah D, Pradhan P, Borkar M, Lynch H, Backman V,
Developing a minimally invasive and cost-effective prescreening strategy for colon cancer is critical because of the impossibility of conducting colonoscopy on the entire at-risk population. The concept of field carcinogenesis, in which normal-appearing tissue away from a tumor has molecular and, consequently, nano-architectural abnormalities, offers one attractive approach to identify high-risk patients. In this study, we investigated whether the novel imaging technique partial wave spectroscopic (PWS) microscopy could risk-stratify patients harboring precancerous lesions of the colon, using an optically measured biomarker (L(d)) obtained from microscopically normal but nanoscopically altered cells. Rectal epithelial cells were examined from 146 patients, including 72 control patients, 14 patients with diminutive adenomas, 20 patients with nondiminutive/nonadvanced adenomas, 15 patients with advanced adenomas/high-grade dysplasia, 12 patients with genetic mutation leading to Lynch syndrome, and 13 patients with cancer. We found that the L(d) obtained from rectal colonocytes was well correlated with colon tumorigenicity in our patient cohort and in an independent validation set of 39 additional patients. Therefore, our findings suggest that PWS-measured L(d) is an accurate marker of field carcinogenesis. This approach provides a potential prescreening strategy for risk stratification before colonoscopy.
PMID: 22491589 [PubMed - as supplied by publisher]
JAMA : the journal of the American Medical Association 2012 Jan 11
Authors: Yen EF, Pokhrel B, Bianchi LK, Roy HK, Du H, Patel A, Hall CR, Witt BL,
Microscopic colitis is currently considered to harbor no increased risk for colorectal cancer, based on a few small studies with limited long-term follow-up. Our aim was to identify patients with microscopic colitis, and to compare long-term rates of colorectal cancer or adenoma to a control group of patients without microscopic colitis.
We reviewed the records of patients diagnosed with microscopic colitis, as identified by a hospital-based pathology database from January 2000 to August 2008. Clinical factors, including history of adenoma or adenocarcinoma, and all colonoscopy findings, were recorded. Age and gender-matched patients without microscopic colitis served as the control in a 1:1 fashion.
A total of 647 patients (153 male: 494 female) were identified with microscopic colitis (MC). Any history of colorectal cancer was detected in 1.92, 1.81, and 4.17% of patients with collagenous colitis (CC), lymphocytic colitis (LC), and controls, respectively (P = 0.095, P = 0.040, P = 0.015 for CC, LC, and all MC, respectively, comparing to controls). Overall, covariate-adjusted risk (odds ratio) of any history of colorectal cancer and colorectal adenoma in MC patients was 0.34 (95% confidence interval [CI] 0.16-0.73, P = 0.006) and 0.52 (95% CI 0.50-0.76, P < 0.0001), respectively. The mean duration of follow-up was 4.63 years, with 147/647 (22.7%) of patients with clinical follow-up >7 years.
In this case-control study involving a large retrospective cohort, microscopic colitis is negatively associated with the risk for colorectal cancer and adenoma. Further studies are required to determine a temporal relationship between microscopic colitis and the future development of colorectal neoplasia.
PMID: 22235076 [PubMed - as supplied by publisher]
Archives of internal medicine 2010 Jul 12
Authors: Roy HK, Gomes AJ, Ruderman S, Bianchi LK, Goldberg MJ, Stoyneva V, Rogers JD, Turzhitsky V, Kim Y, Yen E, Jameel M, Bogojevic A, Backman V,
Flexible sigmoidoscopy is a robust, clinically validated, and widely available colorectal cancer screening technique that is currently sanctioned by major guideline organizations. Given that endoscopic visualization is generally limited to the distal third of the colon and women tend to have a proclivity for proximal lesions, the flexible sigmoidoscopy performance is markedly inferior in women than in men. Our group has shown that by using a novel light-scattering approach, we were able to detect an early increase in blood supply (EIBS) in the distal colonic mucosa, which served as a marker of field carcinogenesis and, hence, proximal neoplasia. Therefore, we sought to ascertain whether rectal EIBS would improve flexible sigmoidoscopy, especially in women. A polarization-gated spectroscopy fiber-optic probe was used to assess EIBS in the endoscopically normal rectum (n = 366). When compared with gender-matched neoplasia-free controls, females with advanced proximal neoplasia (n = 10) had a robust (60%; P = 0.002) increase in rectal mucosal oxyhemoglobin content whereas the effect size in males was less marked (33%; P = 0.052). In women, addition of rectal oxyhemoglobin tripled the sensitivity for advanced neoplasia over flexible sigmoidoscopy alone. Indeed, the performance characteristics seemed to be excellent (sensitivity, 100%; specificity, 76.8%; positive predictive value, 32.6%; and negative predictive value, 100%). A variety of nonneoplastic factors were assessed and did not confound the relationship between rectal EIBS and advanced neoplasia. Therefore, using rectal EIBS in combination with flexible sigmoidoscopy mitigated the gender gap and may allow flexible sigmoidoscopy to be considered as a viable colorectal cancer screening test in women.
PMID: 20625019 [PubMed - as supplied by publisher]
JAMA : the journal of the American Medical Association 2009 Oct 21
Authors: Gomes AJ, Roy HK, Turzhitsky V, Kim Y, Rogers JD, Ruderman S, Stoyneva V, Goldberg MJ, Bianchi LK, Yen E, Kromine A, Jameel M, Backman V,
Endoscopic examination has proven effective in both detecting and preventing colorectal cancer; however, only about a quarter of eligible patients undergo screening. Even if the compliance rate increased, limited endoscopic capacity and cost would be prohibitive. There is a need for an accurate method to target colonoscopy to those most at risk of harboring colonic neoplasia. Exploiting field carcinogenesis seems to be a promising avenue. Our group recently reported that an early increase in blood supply (EIBS) is a reliable marker of field carcinogenesis in experimental models. We now investigate whether in situ detection of EIBS in the rectum can predict neoplasia elsewhere in the colon.
We developed a novel polarization-gated spectroscopy fiber-optic probe that allows depth-selective interrogation of microvascular blood content. Using the probe, we examined the blood content in vivo from the rectal mucosa of 216 patients undergoing screening colonoscopy.
Microvascular blood content was increased by approximately 50% in the endoscopically normal rectal mucosa of patients harboring advanced adenomas when compared with neoplasia-free patients irrespective of lesion location. Demographic factors and nonneoplastic lesions did not confound this observation. Logistic regression using mucosal oxyhemoglobin concentration and patient age resulted in a sensitivity of 83%, a specificity of 82%, and an area under the receiver operating characteristic curve of 0.88 for the detection of advanced adenomas.
Increased microvascular blood supply in the normal rectal mucosa is associated with the presence of clinically significant neoplasia elsewhere in the colon, supporting the development of rectal EIBS as a colon cancer risk-stratification tool.
PMID: 19843905 [PubMed - as supplied by publisher]
JAMA : the journal of the American Medical Association 2008 Sep 24
Authors: Bianchi LK, Burke CA,
After a polyp or polyps are discovered on colonoscopy, many patients are being told to come back for repeat colonoscopy unnecessarily soon, thus diverting a scarce resource away from patients who may derive the most benefit--those with high-risk polyps and those who have never been screened.
PMID: 18812539 [PubMed - as supplied by publisher]