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Su2033 Volumetric Laser Endomicroscopy (VLE) Demonstrates Clinical Benefit When Used During Surveillance Following Ablation of Barrett's Esophagus
Su2032
A total of 71 VLE procedures were performed during the study period. Fifty procedures on 41 patients were done for post-ablation surveillance (83% male, mean age 63.3 years). Preablation mean Prague C and M scores were 2.0 and 4.3 cm, respectively. Original dysplasia grades included intramucosal carcinoma or high grade dysplasia (51.2%), low grade dysplasia (24.4%) and non-dysplastic BE (24.4%). Prior treatments included radiofrequency ablation (90%), liquid nitrogen spray cryotherapy (36.6%) and endoscopic mucosal resection (22.0%). Of the 21 cases with suspicious findings on VLE, 6 (29%) had residual or recurrent BE present on tissue sampling. Four of these cases had visually normal endoscopies. In 28 cases where neither visual inspection nor VLE findings raised concern for recurrence, BE was present in only 5 cases. In 4 cases, BE was found only with WATS3D, and in the other case only on forceps biopsy. In all 5 cases, BE was described on pathology as a "single" or "isolated" focus without widespread metaplasia. Conclusions: VLE demonstrates a clinical benefit when used in patients who have completed endoscopic BE ablation. In 29% of patients with suspicious findings on VLE, residual or recurrent BE was confirmed on pathology. Improved targeted sampling of abnormal VLE findings will only increase this yield. Negative VLE scans were confirmed on histology in 82% of cases, with the remaining cases showing only small foci of BE on histology. These were the first cases performed using VLE at this institution. Additional user experience should only increase the utility of VLE in post-ablation and other patients.
AGA Abstracts
Differential Early Metabolic Changes in Colon Carcinogenesis for Health Disparities: Physiological and Molecular Evidence Tian Gao, Mart DeLaCruz, Andrew Radosevich, Bradley R. Gould, Vadim Backman, Hemant K. Roy Background: Epidemiologic data unequivocally demonstrate a 23% higher incidence in colonic neoplasia in blacks with concomitant 50% increase in colorectal (CRC) mortality compared to whites. However, the biological basis for this has been largely unexplored. The role of early metabolic alterations such as the Warburg effect is clearly appreciated in established cancers however it is not known in early neoplasia. Given that metabolic CRC risk factors (i.e. diabetes, obesity) disproportionately impact blacks, we used polarizationgated spectroscopy (PGS) to examine the microvascular blood flow as a surrogate of metabolic dysregulation in early neoplastic transformation. To explore potential molecular correlates behind PGS, we chose to investigate two master regulators of early CRC, Sirt 6 and Hif-1α, which couple metabolic dysregulation (Sebastian et al., Cell 2012). Methods: For this study we used a fiberoptic PGS probe to measure oxyhemoglobin (OHb) and deoxyhemoglobin (DHb) within rectal microvasculature in 80 prospectively recruited black patients. We compared results to a previous cohort of ~120 white patients in the superficial mucosa (~150μm). We assessed Sirt 6 and Hif-1α expression from rectal biopsies of 80 patients by RT-PCR. Field carcinogenesis was defined as presence of molecular changes in advanced adenomas (AAs) evident elsewhere in the colon. Results: In blacks, there was a striking induction in DHb (220% of control) with OHb being more muted (150% of control). Thus, from a diagnostic perspective, DHb appears to be a stronger marker than OHb. This was in contradistinction to whites, where only OHb was statistically significant with diagnostic potential. The molecular basis of this finding was supported by metabolic regulators, Sirt 6 and Hif-1α, in blacks. The reduced expression of Sirt6 mRNA (Figure 1) appears to give a marked induction of Hif-1α mRNA(Figure 2). Conclusions: We demonstrate herein, for the first time, that there differential metabolic changes in blacks than whites. This was supported physiologically with differential diagnostic effects of DHb versus OHb which implies altered oxygen extraction consonant with Warburg effect. The molecular underpinnings may be related to the key metabolic sensor, Sirt 6 through control of Hif-1α. This work provides potentially important insights into the pathogenesis of CRC disparities and demonstrates the power of optical spectroscopy provide physiological common denominator of the myriad of complex molecular alterations in early carcinogenesis.
Su2034 Automated Optical Coherence Tomography Image Processing for Three Dimensional Detection and Visualization of Subsurface Glands in Barrett's Esophagus With Dysplasia Zhao Wang, Hsiang-Chieh Lee, Michael G. Giacomelli, Kaicheng Liang, Osman O. Ahsen, Marisa Figueiredo, Qin Huang, James G. Fujimoto, Hiroshi Mashimo BACKGROUND/AIMS: Barrett's esophagus (BE) is associated with gastroesophageal reflux disease and BE with dysplasia confers an increased risk of esophageal adenocarcinoma. BE with dysplasia is treated by radio frequency ablation (RFA), and subsquamous buried glands may be a marker for treatment response or recurrence. Previous studies showed that optical coherence tomography (OCT) is well suited for imaging buried glands which are not visible by conventional endoscopy or underappreciated by biopsy. With the development of commercial OCT instruments using a balloon imaging probe, it is possible to image large areas of the esophagus. However, the time-consuming manual analysis required to assess buried glands in OCT images has limited clinical studies. We report an image processing method that enables automated detection, 3-D visualization and quantification of subsurface glands in the esophagus using data from a commercial OCT system. METHODS: Volumetric OCT data, volumetric laser endomicroscopy, at the gastroesophageal junction (GEJ) of patients previously treated with RFA was acquired by a commercially available OCT system (NvisionVLE Imaging system, NinePoint Medical, Inc.) at the VA Boston Healthcare System (Boston, MA). The 36cm2 surface field of view of the OCT imaging balloon enables comprehensive investigation of substructural features. Image processing algorithms were developed to partially correct the cardiac motion and to exactly find the esophageal surface. A machine learning algorithm was used to automatically identify the subsurface glands from the volumetric OCT data. Each volumetric OCT dataset consists of 1200 OCT frames with a total of 10 billion voxels and manual analysis is not feasible. The automatically detected glands were quantified and visualized in 3D. We applied image processing to assess the gland distribution of patients who had complete remission of intestinal metaplasia (CRIM) after RFA to assess treatment response. RESULTS: The figures show representative data from a patient with CRIM, but with recurrent BE on later follow up. Subsurface glands were automatically identified by the algorithm as shown in Fig. 1(a). The segmented glands along with the entire OCT volume were unwrapped to an en face view and 3D rendered to visualize the gland distribution (Fig. 1(b-c)). The total number of subsurface glands as well as the gland volume is higher at four month follow-up as compared to two month follow-up (Fig. 1(b-c)), consistent with BE progression. The glands were denser around the GEJ region. CONCLUSIONS: Image processing using a machine learning method enables comprehensive visualization and quantification of subsurface glands of esophagus with an unprecedented field of view. This method can be applied to existing clinical OCT data and could be an important tool for evaluating disease progression and treatment response.
Figure 1
Figure 2 Su2033 Volumetric Laser Endomicroscopy (VLE) Demonstrates Clinical Benefit When Used During Surveillance Following Ablation of Barrett's Esophagus Natalya Iorio, Alexandra H. Weiss, Michael S. Smith Background: Volumetric laser endomicroscopy (VLE) is an intraluminal imaging modality based on optical coherence tomography, where near-infrared light reflectivity is used to construct cross-sectional images with resolution down to 7 micrometers. This technique can distinguish between squamous and glandular tissue, as well as identify features concerning for dysplasia and neoplasia. Early use has identified a clinical benefit in the diagnosis and staging of Barrett's esophagus (BE). Our aim was to evaluate the utility of VLE in surveillance following endoscopic BE ablation at a high volume center. Methods: All patients who had upper endoscopy with VLE from May through November 2014 were considered for analysis. Patients were included if VLE was performed as part of post-BE ablation surveillance endoscopy and pathology results were available. All patients had Wide Area Transepithelial Sampling with Computer-Assisted 3-Dimensional Tissue Analysis (WATS3D) brush biopsies and 4-quadrant large capacity forceps biopsies every centimeter throughout the original BE segment during the same procedure. Demographic, historical, endoscopic and histologic data were collected for each patient, de-identified and aggregated prior to analysis. Results:
AGA Abstracts
Figure 1. Automated detection and 3D visualization of subsurface glands in a patient with recurrent BE after CRIM. (a) A cross-sectional OCT image shows the automatically detected (yellow) subsurface glands. Horizontal scale bar: 1 cm, vertical scale bar: 1 mm. (b) 3D en face map of esophagus shows gland distribution (blue) in the patient at two month followup after CRIM. (c) Four month follow-up shows increased glands near the GEJ. The dotted
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A total of 71 VLE procedures were performed during the study period. Fifty procedures on 41 patients were done for post-ablation surveillance (83% male, mean age 63.3 years). Preablation mean Prague C and M scores were 2.0 and 4.3 cm, respectively. Original dysplasia grades included intramucosal carcinoma or high grade dysplasia (51.2%), low grade dysplasia (24.4%) and non-dysplastic BE (24.4%). Prior treatments included radiofrequency ablation (90%), liquid nitrogen spray cryotherapy (36.6%) and endoscopic mucosal resection (22.0%). Of the 21 cases with suspicious findings on VLE, 6 (29%) had residual or recurrent BE present on tissue sampling. Four of these cases had visually normal endoscopies. In 28 cases where neither visual inspection nor VLE findings raised concern for recurrence, BE was present in only 5 cases. In 4 cases, BE was found only with WATS3D, and in the other case only on forceps biopsy. In all 5 cases, BE was described on pathology as a "single" or "isolated" focus without widespread metaplasia. Conclusions: VLE demonstrates a clinical benefit when used in patients who have completed endoscopic BE ablation. In 29% of patients with suspicious findings on VLE, residual or recurrent BE was confirmed on pathology. Improved targeted sampling of abnormal VLE findings will only increase this yield. Negative VLE scans were confirmed on histology in 82% of cases, with the remaining cases showing only small foci of BE on histology. These were the first cases performed using VLE at this institution. Additional user experience should only increase the utility of VLE in post-ablation and other patients.
AGA Abstracts
Differential Early Metabolic Changes in Colon Carcinogenesis for Health Disparities: Physiological and Molecular Evidence Tian Gao, Mart DeLaCruz, Andrew Radosevich, Bradley R. Gould, Vadim Backman, Hemant K. Roy Background: Epidemiologic data unequivocally demonstrate a 23% higher incidence in colonic neoplasia in blacks with concomitant 50% increase in colorectal (CRC) mortality compared to whites. However, the biological basis for this has been largely unexplored. The role of early metabolic alterations such as the Warburg effect is clearly appreciated in established cancers however it is not known in early neoplasia. Given that metabolic CRC risk factors (i.e. diabetes, obesity) disproportionately impact blacks, we used polarizationgated spectroscopy (PGS) to examine the microvascular blood flow as a surrogate of metabolic dysregulation in early neoplastic transformation. To explore potential molecular correlates behind PGS, we chose to investigate two master regulators of early CRC, Sirt 6 and Hif-1α, which couple metabolic dysregulation (Sebastian et al., Cell 2012). Methods: For this study we used a fiberoptic PGS probe to measure oxyhemoglobin (OHb) and deoxyhemoglobin (DHb) within rectal microvasculature in 80 prospectively recruited black patients. We compared results to a previous cohort of ~120 white patients in the superficial mucosa (~150μm). We assessed Sirt 6 and Hif-1α expression from rectal biopsies of 80 patients by RT-PCR. Field carcinogenesis was defined as presence of molecular changes in advanced adenomas (AAs) evident elsewhere in the colon. Results: In blacks, there was a striking induction in DHb (220% of control) with OHb being more muted (150% of control). Thus, from a diagnostic perspective, DHb appears to be a stronger marker than OHb. This was in contradistinction to whites, where only OHb was statistically significant with diagnostic potential. The molecular basis of this finding was supported by metabolic regulators, Sirt 6 and Hif-1α, in blacks. The reduced expression of Sirt6 mRNA (Figure 1) appears to give a marked induction of Hif-1α mRNA(Figure 2). Conclusions: We demonstrate herein, for the first time, that there differential metabolic changes in blacks than whites. This was supported physiologically with differential diagnostic effects of DHb versus OHb which implies altered oxygen extraction consonant with Warburg effect. The molecular underpinnings may be related to the key metabolic sensor, Sirt 6 through control of Hif-1α. This work provides potentially important insights into the pathogenesis of CRC disparities and demonstrates the power of optical spectroscopy provide physiological common denominator of the myriad of complex molecular alterations in early carcinogenesis.
Su2034 Automated Optical Coherence Tomography Image Processing for Three Dimensional Detection and Visualization of Subsurface Glands in Barrett's Esophagus With Dysplasia Zhao Wang, Hsiang-Chieh Lee, Michael G. Giacomelli, Kaicheng Liang, Osman O. Ahsen, Marisa Figueiredo, Qin Huang, James G. Fujimoto, Hiroshi Mashimo BACKGROUND/AIMS: Barrett's esophagus (BE) is associated with gastroesophageal reflux disease and BE with dysplasia confers an increased risk of esophageal adenocarcinoma. BE with dysplasia is treated by radio frequency ablation (RFA), and subsquamous buried glands may be a marker for treatment response or recurrence. Previous studies showed that optical coherence tomography (OCT) is well suited for imaging buried glands which are not visible by conventional endoscopy or underappreciated by biopsy. With the development of commercial OCT instruments using a balloon imaging probe, it is possible to image large areas of the esophagus. However, the time-consuming manual analysis required to assess buried glands in OCT images has limited clinical studies. We report an image processing method that enables automated detection, 3-D visualization and quantification of subsurface glands in the esophagus using data from a commercial OCT system. METHODS: Volumetric OCT data, volumetric laser endomicroscopy, at the gastroesophageal junction (GEJ) of patients previously treated with RFA was acquired by a commercially available OCT system (NvisionVLE Imaging system, NinePoint Medical, Inc.) at the VA Boston Healthcare System (Boston, MA). The 36cm2 surface field of view of the OCT imaging balloon enables comprehensive investigation of substructural features. Image processing algorithms were developed to partially correct the cardiac motion and to exactly find the esophageal surface. A machine learning algorithm was used to automatically identify the subsurface glands from the volumetric OCT data. Each volumetric OCT dataset consists of 1200 OCT frames with a total of 10 billion voxels and manual analysis is not feasible. The automatically detected glands were quantified and visualized in 3D. We applied image processing to assess the gland distribution of patients who had complete remission of intestinal metaplasia (CRIM) after RFA to assess treatment response. RESULTS: The figures show representative data from a patient with CRIM, but with recurrent BE on later follow up. Subsurface glands were automatically identified by the algorithm as shown in Fig. 1(a). The segmented glands along with the entire OCT volume were unwrapped to an en face view and 3D rendered to visualize the gland distribution (Fig. 1(b-c)). The total number of subsurface glands as well as the gland volume is higher at four month follow-up as compared to two month follow-up (Fig. 1(b-c)), consistent with BE progression. The glands were denser around the GEJ region. CONCLUSIONS: Image processing using a machine learning method enables comprehensive visualization and quantification of subsurface glands of esophagus with an unprecedented field of view. This method can be applied to existing clinical OCT data and could be an important tool for evaluating disease progression and treatment response.
Figure 1
Figure 2 Su2033 Volumetric Laser Endomicroscopy (VLE) Demonstrates Clinical Benefit When Used During Surveillance Following Ablation of Barrett's Esophagus Natalya Iorio, Alexandra H. Weiss, Michael S. Smith Background: Volumetric laser endomicroscopy (VLE) is an intraluminal imaging modality based on optical coherence tomography, where near-infrared light reflectivity is used to construct cross-sectional images with resolution down to 7 micrometers. This technique can distinguish between squamous and glandular tissue, as well as identify features concerning for dysplasia and neoplasia. Early use has identified a clinical benefit in the diagnosis and staging of Barrett's esophagus (BE). Our aim was to evaluate the utility of VLE in surveillance following endoscopic BE ablation at a high volume center. Methods: All patients who had upper endoscopy with VLE from May through November 2014 were considered for analysis. Patients were included if VLE was performed as part of post-BE ablation surveillance endoscopy and pathology results were available. All patients had Wide Area Transepithelial Sampling with Computer-Assisted 3-Dimensional Tissue Analysis (WATS3D) brush biopsies and 4-quadrant large capacity forceps biopsies every centimeter throughout the original BE segment during the same procedure. Demographic, historical, endoscopic and histologic data were collected for each patient, de-identified and aggregated prior to analysis. Results:
AGA Abstracts
Figure 1. Automated detection and 3D visualization of subsurface glands in a patient with recurrent BE after CRIM. (a) A cross-sectional OCT image shows the automatically detected (yellow) subsurface glands. Horizontal scale bar: 1 cm, vertical scale bar: 1 mm. (b) 3D en face map of esophagus shows gland distribution (blue) in the patient at two month followup after CRIM. (c) Four month follow-up shows increased glands near the GEJ. The dotted
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