Optical Measurement of Rectal Microvasculature as an Adjunct to Flexible Sigmoidosocopy: Gender-Specific Implications
ABSTRACT 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.
SourceAvailable from: PubMed Central[Show abstract] [Hide abstract]
ABSTRACT: The process of neoplastic transformation of the colon involves a progression through hyperproliferative epithelium through the aberrant crypt foci→small adenoma→large adenoma→invasive cancer→metastatic disease. These are orchestrated by sequential genetic and epigenetic events which provide the underpinnings of cellular alterations such as early induction in proliferation/suppression of apoptosis, along with the late stage increase in invasiveness. Colorectal cancer (CRC) averages 49-111 mutations per tumor encompassing 10-15 critical signaling pathways. Accumulating such a high number of mutations requires a fertile mutational field, which is the hallmark of colon carcinogenesis. While genetic susceptibility to colorectal cancer is well-known, at least half of the risk is believed to be due to exogeneous factors (e.g., obesity, diet, exercise). Understanding these risk factors represents a promising mode of tailoring screening modality and intensity. However, previous attempts using these factors (i.e., NCI risk calculator) have only been modestly successful with an area under receiver operating characteristics (ROC) curve (AUC) of just 0.61. One of the most important concepts is that risk is the interaction between these genetic and environmental components and is driven by the variety of polymorphisms. Thus, predicting risk is difficult given the complexity. On the other hand, the colonic mucosa represents the end product of the complex interplay between these multiple factors. The power of field carcinogenesis is that it reflects this interplay between genetics and environment.03/2013; 4(3):251-61. DOI:10.7150/jca.5838
[Show abstract] [Hide abstract]
ABSTRACT: Background: According to the field effect theory, by detecting microvasculature changes such as early increase in blood supply (EIBS) in the surrounding tissue, neoplastic lesions can be identified from a distance. Objective: To determine the feasibility and efficacy of a fiberoptic probe containing novel polarization gating spectroscopy technology to identify patients with pancreatic adenocarcinoma (PAC) by the field effect theory. Design: Prospective cohort (pilot) study. Setting: Outpatient tertiary care center. Patients: Adult (>= 18 years) patients undergoing EGD-EUS were screened. Patients with PAC were included in the "cancer" group and patients without PAC were included in the "control" group. We excluded patients with other known malignancies and gastroduodenal premalignant lesions. Interventions and Main Outcome Measures: Spectroscopic measurements of EIBS variables, such as deoxyhemoglobin concentration (DHb) and mean blood vessel radius (BVR), were obtained from 5 periampullary locations. The Mann-Whitney rank sum test was used for the statistical analysis (P <= .05). Results: Fourteen patients (mean age 72 years, 79% male) in the cancer group and 15 patients (mean age 63 years, 60% male) in the control group were included in the final analysis. At the ampullary site, both DHb (P = .001) and BVR (P = .03) were higher in PAC patients than in the control subjects. The DHb alone (92% sensitivity, 86% specificity) or in combination with BVR (92% sensitivity, 79% specificity) can differentiate PAC from control subjects with high accuracy. Limitations: Small sample size, unmatched control subjects. Conclusions: Spectroscopic measurements of EIBS by fiberoptic probes are feasible. Preliminary evidence suggests that in vivo measurement of normal-appearing duodenal tissue can differentiate PAC patients from a distance with high accuracy.Gastrointestinal Endoscopy 05/2014; 80(5). DOI:10.1016/j.gie.2014.03.031 · 4.90 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Field carcinogenesis is the initial stage of cancer progression. Understanding field carcinogenesis is valuable for both cancer biology and clinical medicine. Here, we used inverse spectroscopic optical coherence tomography to study colorectal cancer (CRC) and pancreatic cancer (PC) field carcinogenesis. Depth-resolved optical and ultrastructural properties of the mucosa were quantified from histologically normal rectal biopsies from patients with and without colon adenomas (n=85) as well as from histologically normal peri-ampullary duodenal biopsies from patients with and without PC (n=22). Changes in the epithelium and stroma in CRC field carcinogenesis were separately quantified. In both compartments, optical and ultra-structural alterations were consistent. Optical alterations included lower backscattering (μb) and reduced scattering (μs') coefficients and higher anisotropy factor g. Ultrastructurally pronounced alterations were observed at length scales up to ∼450 nm, with the shape of the mass density correlation function having a higher shape factor D, thus implying a shift to larger length scales. Similar alterations were found in the PC field carcinogenesis despite the difference in genetic pathways and etiologies. We further verified that the chromatin clumping in epithelial cells and collagen cross-linking caused D to increase in vitro and could be among the mechanisms responsible for the observed changes in epithelium and stroma, respectively.Journal of Biomedical Optics 03/2014; 19(3):36013. DOI:10.1117/1.JBO.19.3.036013 · 2.75 Impact Factor