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 (CRC) screening technique that is currently sanctioned by both 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, flexible sigmoidoscopy’s performance is markedly inferior in women than men. Our group has demonstrated 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 utilized to assess EIBS in the endoscopically-normal rectum (n=366). When compared to gender-matched neoplasia-free controls, females with advanced proximal neoplasia (n=10) had a robust (60%, p=0.002) increase in rectal mucosal oxyhemoglobin (OHb) content (p = 0.001) whereas the effect size in males was less marked (33%, p=0.052). In women, addition of rectal OHb tripled the sensitivity for advanced neoplasia over flexible sigmoidoscopy alone. Indeed, the performance characteristics appeared to be excellent (sensitivity=100%, specificity=76.8%, positive predictive value =32.6% and negative predictive value of 100%). A variety of non-neoplastic 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 a viable CRC screening test in women.

Colonic Mucosal Fatty Acid Synthase as an Early Biomarker for Colorectal Neoplasia: Modulation by Obesity and Gender

“…The increased FASN in males versus females suggests that this colonic neoplasia biomarker may have a significant gender predilection. There is precedence for significant gender based biomarker specificity as can be seen in serum (C-reactive protein) [27] as well as from field carcinogenesis data (biophotonically derived or advanced adenomas) [28]. …”

Neo-angiogenesis and the premalignant micro-circulatory augmentation of early colon carcinogenesis

“…Thus, developing a minimally intrusive pre-screening technique could substantially undermine the need for colonoscopy. We have published in situ data from over 700 subjects that confirms the promise of this approach (for advanced adenomas the area under the receiver operator curve was ~0.90)[14,35]. We envision simplifying our probes to the extent that they could be used at the primary care physician's office during annual rectal examination to effectively risk-stratify the population for colorectal cancer.…”

“…We then demonstrated EIBS clinically using developed an endoscopically-compatible 4D-ELF fiber-optic probe in patients undergoing colonoscopy (2). Importantly, EIBS was detectable in the visually normal rectum in patients harboring advanced adenomas elsewhere in the colon (3)[14], thus suggesting applications as a minimally-intrusive risk-stratification.…”

Nanocytology of Rectal Colonocytes to Assess Risk of Colon Cancer Based on Field Cancerization

“…As outlined in Table 2, smoking and drinking history also did not have any confounding effect on L d ( P = 0.57 for current smokers and P = 0.99 for drinking). Similarly, male gender is a well-established risk factor for colonic neoplasia(32). However, ANCOVA analysis indicated that there was no significant confounding with gender ( P = 0.29 for L d ).…”