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  • American Association for Cancer Research (AACR)  (5)
  • 1
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 15, No. 9 ( 2009-05-01), p. 3110-3117
    Abstract: Purpose: 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. Experimental Design: 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. Results: Microvascular blood content was increased by ∼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. Conclusions: 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.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 69, No. 10 ( 2009-05-15), p. 4476-4483
    Abstract: Field carcinogenesis detection represents a promising means for colorectal cancer (CRC) screening, although current techniques (e.g., flexible sigmoidoscopy) lack the requisite sensitivity. The novel optical technology low-coherence enhanced backscattering (LEBS) spectroscopy, allows identification of microscale architectural consequences of the field carcinogenesis in preclinical CRC models with unprecedented accuracy. To investigate the potential clinical translatability of this approach, we obtained biopsies from the normal-appearing rectal mucosa from patients undergoing colonoscopy (n = 219). LEBS signals were recorded through a bench-top instrument. Four parameters characterizing LEBS signal were linearly combined into a single marker. We found that LEBS signal parameters generally mirrored neoplasia progression from patients with no neoplasia, to 5 to 9 mm adenoma and to advanced adenomas. The composite LEBS marker calculated from the LEBS signal paralleled this risk status (ANOVA P & lt; 0.001). Moreover, this was independent of CRC risk factors, benign colonic findings, or clinically unimportant lesions (diminutive adenomas, hyperplastic polyps). For advanced adenomas, the LEBS marker had a sensitivity of 100%, specificity of 80%, and area under the receiver operator characteristic curve of 0.895. Leave-one-out cross-validation and an independent data set (n = 51) supported the robustness of these findings. In conclusion, we provide the first demonstration that LEBS-detectable alterations in the endoscopically normal rectum were associated with the presence of neoplasia located elsewhere in the colon. This study provides the proof of concept that rectal LEBS analysis may potentially provide a minimally intrusive CRC screening technique. Further studies with an endoscopically compatible fiber optic probe are under way for multicenter clinical validation. [Cancer Res 2009;69(10):4476–83]
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2009
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 3
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 20 ( 2010-10-15), p. 7748-7754
    Abstract: We have recently developed a novel optical technology, partial wave spectroscopic (PWS) microscopy, which is exquisitely sensitive to the nanoarchitectural manifestation of the genetic/epigenetic alterations of field carcinogenesis. Our approach was to screen for lung cancer by assessing the cheek cells based on emerging genetic/epigenetic data which suggests that the buccal epithelium is altered in lung field carcinogenesis. We performed PWS analysis from microscopically normal buccal epithelial brushings from smokers with and without lung cancer (n = 135). The PWS parameter, disorder strength of cell nanoarchitecture (Ld), was markedly ( & gt;50%) elevated in patients harboring lung cancer compared with neoplasia-free smokers. The performance characteristic was excellent with an area under the receiver operator characteristic curve of & gt;0.80 and was equivalent for both disease stage (early versus late) and histologies (small cell versus non–small cell lung cancers). An independent data set validated the findings with only a minimal degradation of performance characteristics. Our results offer proof of concept that buccal PWS may potentially herald a minimally intrusive prescreening test that could be integral to the success of lung cancer population screening programs. Cancer Res; 70(20); 7748–54. ©2010 AACR.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2036785-5
    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
    Location Call Number Limitation Availability
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  • 4
    In: Clinical Cancer Research, American Association for Cancer Research (AACR), Vol. 21, No. 19 ( 2015-10-01), p. 4347-4355
    Abstract: Purpose: Colorectal cancer remains the second leading cause of cancer deaths in the United States despite being eminently preventable by colonoscopy via removal of premalignant adenomas. In order to more effectively reduce colorectal cancer mortality, improved screening paradigms are needed. Our group pioneered the use of low-coherence enhanced backscattering (LEBS) spectroscopy to detect the presence of adenomas throughout the colon via optical interrogation of the rectal mucosa. In a previous ex vivo biopsy study of 219 patients, LEBS demonstrated excellent diagnostic potential with 89.5% accuracy for advanced adenomas. The objective of the current cross-sectional study is to assess the viability of rectal LEBS in vivo. Experimental Design: Measurements from 619 patients were taken using a minimally invasive 3.4-mm diameter LEBS probe introduced into the rectum via anoscope or direct insertion, requiring approximately 1 minute from probe insertion to withdrawal. The diagnostic LEBS marker was formed as a logistic regression of the optical reduced scattering coefficient \mu_s^* and mass density distribution factor D. Results: The rectal LEBS marker was significantly altered in patients harboring advanced adenomas and multiple non-advanced adenomas throughout the colon. Blinded and cross-validated test performance characteristics showed 88% sensitivity to advanced adenomas, 71% sensitivity to multiple non-advanced adenomas, and 72% specificity in the validation set. Conclusions: We demonstrate the viability of in vivo LEBS measurement of histologically normal rectal mucosa to predict the presence of clinically relevant adenomas throughout the colon. The current work represents the next step in the development of rectal LEBS as a tool for colorectal cancer risk stratification. Clin Cancer Res; 21(19); 4347–55. ©2015 AACR.
    Type of Medium: Online Resource
    ISSN: 1078-0432 , 1557-3265
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2015
    detail.hit.zdb_id: 1225457-5
    detail.hit.zdb_id: 2036787-9
    Location Call Number Limitation Availability
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  • 5
    In: Cancer Prevention Research, American Association for Cancer Research (AACR), Vol. 3, No. 7 ( 2010-07-01), p. 844-851
    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. Cancer Prev Res; 3(7); 844–51. ©2010 AACR.
    Type of Medium: Online Resource
    ISSN: 1940-6207 , 1940-6215
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
    detail.hit.zdb_id: 2422346-3
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