- Email: [email protected]
Su2028 Unique Expression of Adipose Triglyceride Lipase (ATGL) in Low Grade Colorectal Carcinoma
AGA Abstracts
Su2025
cancer patients with occlusion of the pancreatic duct can be reduced or prevented by PEST. Methods This was a double blind, randomized phase II study. Sixty seven patients with unresectable pancreatic cancer were randomized to receive either enteric coated PEST or placebo. The high dose enteric coated pancreatic enzyme preparation under investigation was 6-9 capsules of pancreatin 457.7mg per day. Patients used two capsules three times daily during main meals and one capsule three times daily during snacks between main meals. The primary endpoint was the percentage change in body weight at eight weeks after the randomization. Results There was no significant difference in the percentage change in body weight between PEST and placebo groups. Patients on pancreatic enzyme lost 1.49% (1.12kg) body weights whereas patients on placebo lost 2.99% (1.63%) (p=0.381). The difference in the percent change of scored Patient-Generated Subjective Global Assessment (PG-SGA) was not significant between two groups (8.85% vs. 15.69%, p=0.18). Subgroup analyses according to the tumor location showed that, in patients with unresectable pancreatic head cancer, the percent change of PG-SGA score was -42.65% in PEST group and 32.93% in placebo group (p=0.0393). Conclusions PEST did not reduce weight loss in unresectable pancreatic cancer patients. However, findings from these results indicate that PEST has the potential to improve nutritional status in patients with unresectable pancreatic head cancer. The effect of PEST on weight loss in patients with pancreatic head cancer should be assessed in a larger randomized trial.
Increased Insulin Resistance Is Not Seen After Recently Diagnosed Colorectal Cancer: A National Health and Nutrition Examination Survey (NHANES) Study Kenneth Obi, Alice Hinton, Razvan Arsenescu, Peter P. Stanich, Darrell M. Gray, Somashekar G. Krishna, Samer El-Dika, Hisham Hussan Background: Increased insulin resistance (IR) was shown to be associated with an increased risk of colorectal cancer (CRC). It is unknown if the onset of CRC impacts insulin resistance after diagnosis. Objective: To determine the association between IR and recently diagnosed CRC in a US representative cohort. Methods: We conducted a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES, 1999 - 2010). IR was determined using the homeostasis model assessment (HOMA-IR) and was classified as the upper quartile of HOMA-IR ( ≥ 3.52) in this study. We excluded participants who were less than age 20, pregnant, on insulin or insulin lowering medications, or who had colorectal cancer diagnosis older than 4 years from the time of survey. Results: There were a total of 88,373,262 patients in our weighted cohort, 24,250,441 (27.4%) of which had IR. Basic demographics were significantly different between patients with and without IR as shown in Table 1. Patients with IR were more likely to consume alcohol and dietary fat but less likely to smoke tobacco (p<0.05). IR was associated with higher Body Mass Index (BMI), Waist Circumference and elevated C-reactive protein (CRP); however patients with IR reported more intentional weight change and a significant drop in their weight over the year prior to the survey (Table 2). There were 148,040 patients with CRC who were equally distributed between the groups with and without IR (P> 0.05). After adjusting for age, race and gender, the prevalence of recently diagnosed CRC remained similar in both groups (OR 1.00, 95% CI 0.48, 2.06). Conclusion: There is no conclusive association between insulin resistance and the prevalence of recently diagnosed colorectal cancer in this US nationally representative cohort of adults. Further prospective studies are required to investigate whether CRC-related weight loss leads to improved insulin resistance in this population and how that can alter risk of subsequent CRC. Table 1
Su2027 Diabetes, Glucose, and Insulin Levels and Risk of Serrated Polyps and Sessile Serrated Adenomas Seth D. Crockett, Christopher F. Martin, John A. Baron, Robert S. Sandler Introduction: Serrated polyps (SPs) such as sessile serrated adenomas (SSAs) have malignant potential, yet their epidemiology is poorly understood. Some studies have suggested that diabetes may be a risk factor for SSAs but data are conflicting. To better elucidate this association, we aimed to determine whether history of diabetes and insulin and glucose levels were related to risk of serrated polyps and SSAs specifically. Methods: Data from a series of cross-sectional studies of patients undergoing colonoscopy at the University of North Carolina between 1998 and 2010 were pooled to identify patients with SPs and conventional adenomas (CAd). Proximal and large SPs were reviewed by an expert pathologist to determine the presence of SSAs. Demographics and risk factor data were collected by standardized interview. Fasting blood samples were obtained at time of colonoscopy for serum glucose and insulin measurements, performed using standard assays. Bivariate analyses were performed using t-tests and chi-squared or Fisher's Exact tests. Multivariate analyses were performed via logistic regression to estimate ORs and 95% CI comparing polyp groups to those with no polyps, while adjusting for age, sex, study, and year of colonoscopy. Results: We identified 1316 (57%) without polyps, 460 with CAd only (20%), 311 with SPs only (13%), and 78 patients with SSAs (3%) among 2308 participants undergoing colonoscopy. A history of diabetes was not significantly associated with either CAd or SPs. Diabetes was present in 11% of patients with SSAs only vs. 9% of patients without polyps (p=0.7). Mean glucose level was higher in patients with CAd compared to those without polyps (132 mg/ dL vs. 125 mg/dL, p=0.03), but this was not true for those with SSAs only (mean glucose 128 mg/dL, p=0.8 vs. no polyp group). Similarly, mean insulin level was higher in patients with CAd compared to those without polyps (10.5 U/mL vs. 8.8 U/mL, p=0.05), but this did not hold for those with SSAs only (mean insulin level 7.4, p=0.6 vs. no polyp group). In multivariate analysis, higher fasting serum glucose and insulin levels were associated with borderline increased risk of CAd [OR 1.04 (95% CI 1.00, 1.08) and OR 1.01 (95% CI 1.00, 1.03), respectively], but not for SPs or SSAs (Table). Further adjustment for body mass index did not substantially alter the results. Conclusions: In this study, we did not find statistically significant associations between diabetes and SPs or SSAs specifically. Elevated glucose and insulin levels were weakly associated with CAd, but there were no associations between glucose and insulin levels and SPs or SSAs. These data suggest that there is not a strong relationship between diabetes and its associated biochemical alterations and serrated pathway neoplasia.
Univariate analysis of participants with and without insulin resistance. Table 2
*OR per 10 unit increase in glucose level Univariate analysis of metabolic markers in participants with and without insulin resistance.
Su2028 Unique Expression of Adipose Triglyceride Lipase (ATGL) in Low Grade Colorectal Carcinoma Vinit V. Patil, Joanne Rutgers, Xianzhong Ding, mona Cornwell, Megan Roth, Nancy Phillips, Carole Vogler, Susan Crawford, Jinping Lai
Su2026 Efficacy of Pancreatic Enzyme Supplementation Therapy in Patients With Unresectable Pancreatic Cancer Sun Seob Park, Sang Myung Woo, So Young Kim, Jungnam Joo, Seung Hyun Chung, Sooin Yun, Sang Jae Park, Sung-Sik Han, Tae Hyun Kim, Young Hwan Koh, Eun Kyung Hong, Woo Jin Lee
Background: Obesity is associated with increased risk of colorectal adenocarcinoma (CRA) and obese individuals have decreased protein expression of adipose triglyceride lipase (ATGL) and pigment epithelium derived factor (PEDF). Additionally, expression of ATGL and PEDF in the tumor microenvironment is associated with cancer growth and spread. Thus, we hypothesize that altered expression of ATGL and PEDF is associated with CRA. Design: Tumor tissue from 56 patients with CRA and clinical information (age, sex, body mass index and cancer case summary) was stained by immunohistochemistry (IHC) for ATGL and PEDF. Intensity of ATGL and PEDF staining, histologic grade, and parameters including BMI >25, lymphovascular and perineural invasion, metastasis, MMR expression (MLH1,
Background Pancreatic cancer is the fifth leading cause of death from cancer in Korea. Weight loss in pancreatic cancer is associated with maldigestion due to pancreatic duct obstruction and pancreatic enzyme supplementation therapy (PEST) may result in a significant improvement in fat and protein absorption. We planned a prospective, randomized, placebo-controlled trial to verify the hypothesis that weight loss in unresectable pancreatic
AGA Abstracts
S-578
Figure 1. ATGL immunoreactivity in a moderately (A) and a poorly (B) differentiated colonic adenocarcinomas (x400). Su2029 In Vivo Imaging of Mucosal Endothelin-a Receptor Expression to Characterize Murine Colorectal Cancer Development Dominik Bettenworth, Marcus Mücke, Christiane Geyer, Carsten Höltke, Katrin Schwegmann, Christopher Poremba, Michael Schäfers, Dirk Domagk, Philipp Lenz
Representative en face OCT images of different upper GI tissues from depths of 100-400um and projected over 80um. A, normal esophagus. B, gastric mucosa. C, Non-dysplastic BE. D, BE with low grade dysplasia. E, BE with high grade dysplasia. F, Esophageal adenocarcinoma (stage T1). Scale bars are 500um.
BACKGROUND AND AIMS: Ulcerative colitis patients are at an increased risk of developing colorectal cancer. Therefore, current guidelines recommend surveillance colonoscopy with chromoendoscopy or random biopsies to detect dyplastic lesions. ET-A receptor (ETAR) expression is known to be significantly increased in various malignancies including colorectal cancer (1). The aim of the study was to detect and characterize early dysplastic lesions in mice by ETAR-guided fluorescence endoscopy (FE) and fluorescence reflectance imaging. METHODS: Colorectal cancer was induced in C57Bl/6 WT mice (n=15) by single injection of azoxymethane i.p. and cyclic administration of dextran sodiumsulfate in drinking water. A Cy5.5-labeled nonpeptidic ETAR imaging probe was intravenously injected 24 hrs before endoscopic examination. Tumor development was assessed in vivo by white light endoscopy and FE. Murine colons were examined by fluorescence reflectance imaging using an MSFX PRO optical imaging system to measure tracer uptake ex vivo. At the end of the experiment, colons were explanted and tumors were graded after HE staining and evaluated by an expert pathologist. Tumor biology was assessed by immunohistochemistry and western blot analysis of ETAR expression. Additionally, binding specificity of the tracer was evaluated by simultaneous injection of an equimolar amount of an unspecific fluorochrome (Cy3.5-glycin) and the specific tracer. RESULTS: ETAR expression could easily be detected by FE and all animals survived the procedure. Standard histology confirmed colorectal adenomas as well as high and low grade dysplasia. Conventional molecular imaging applying the fluorescent ETAR imaging probe showed significantly increased tracer uptake in colorectal adenoma as compared to healthy mucosa (1336.8 ± 375.3 vs. 544.1 ± 90.4, P < 0.001). In contrast, no significant difference in tracer uptake between low and high grade adenoma was found (tumor-to-background ratio: 2.5 ± 0.6 vs. 2.3 ± 0.9, P = 0.637). The tumor-to-background ratio of lesions imaged for Cy3.5 was significantly reduced as compared to Cy5.5 indicating the high binding-specificity of the used ETAR tracer (1.4 ± 0.3 vs. 2.5 ± 0.7, P < 0.001). CONCLUSION: ETAR expression was significantly increased in murine colorectal dysplasia as compared to healthy mucosa. By detection of ETAR via FE in live mice, a prognostic biomarker for colorectal cancer development is directly visualized during colonoscopy, thus facilitating in vivo tumor characterization on a molecular level. (1) Hoosein et al. Altered endothelin receptor subtypes in colorectal cancer. Eur J Gastroenterol Hepatol. 2007
Su2031 Evaluation of Severity Using Endoscopic Dual Red Imaging Targeting Submucosal Vessel in Patients With Ulcerative Colitis Makoto Naganuma, Naohisa Yahagi, Rieko Bessho, Ai Fujimoto, Naoki Hosoe, Kazuhiro Kashiwagi, Tadakazu Hisamatsu, Haruhiko Ogata, Takanori Kanai Background: Endoscopy is useful to assess the severity of inflammation and can predict middle to long term prognosis in patients with ulcerative colitis (UC). Recently, new imaging technology that has three kinds of illumination lights whose center wavelength are 540nm, 600nm and 630nm respectively. The both of lights in 600nm and 630nm are critical to recognize blood vessels in deeper tissue. Because dual red imaging (DRI) can mainly emphasize the findings of vessel pattern, disagreement for assessment the severity of inflammation using DRI might be minimal among the investigators. The aim of this study is to evaluate the additional usefulness of DRI to assess the severity of inflammation in patients with UC. Patients and Methods: A total of 43 UC patients were enrolled to evaluate endoscopic severity at 112 segments of colon using white light imaging and DRI. Two independent investigators assessed and compared between Matts' endoscopic scores and DRI scores (see Figure). Correlation between DRI score and histological grading (Matts histological score 15) was also evaluated. Furthermore, inter-observer agreement for DRI score between two investigators was also assessed. Results: DRI score is closely correlated to Matts'endoscopic (r=0.88) and histological scores (r=0.83). Although rates of DRI score agreement between 2 investigators was 87% (97/112, κ=0.81), rates of Matts endoscopic score agreement was 72% (81/112, κ=0.59). Among patients with mild to moderate colitis (Matts' endoscopic score 2-3). median Matts histological score in patients with DRI score=4 was significantly higher than that in patients with DRI score=2 or 3 (p<0.01). Conclusion: DRI score is closely correlated to former endoscopic and histological score and inter-observer disagreement of DRI was minimal comparing to Matts' score.
Su2030 En Face Optical Coherence Tomography Visualization of Mucosal Surface Patterns for Identifying Early Malignancy in the Upper GI Tract Osman O. Ahsen, Hsiang-Chieh Lee, Kaicheng Liang, Michael G. Giacomelli, Zhao Wang, Marisa Figueiredo, Qin Huang, Benjamin Potsaid, Vijaysekhar Jayaraman, James G. Fujimoto, Hiroshi Mashimo BACKGROUND/AIMS: Aberrant mucosal surface patterns (pit patterns) are associated with dysplasia in Barrett's esophagus (BE). Optical coherence tomography (OCT) can generate volumetric images of tissue microstructure. We have recently demonstrated ultrahigh-speed endoscopic OCT that achieves >10x faster imaging speeds than commercial systems. This OCT, combined with distal micromotor beam scanning, acquires densely sampled volumetric datasets enabling arbitrary cross-sectional and depth-resolved en face OCT images and shows pit patterns with high resolution and contrast. In this study we investigate en face OCT of upper GI tissues including normal squamous epithelium, gastric mucosa, non-dysplastic BE (NDBE), BE with low and high grade dysplasia, as well as esophageal adenocarcinoma (EAC). METHODS: The study was performed at the VABHS under an IRB protocol approved by the VABHS, HMS and MIT. We used an endoscopic OCT system with a 600 kHz axial scan
S-579
AGA Abstracts
AGA Abstracts
rate and 400 fps frame rate. The imaging probe was introduced in the endoscope accessory port for co-registration of images with biopsies. Volumetric datasets were acquired with an 8 second helical scan over a 160mm2 area, and multiple datasets were acquired covering the BE length. A total of 15 BE patients (7 NDBE, 3 LGD, 4 HGD, 1 EAC) were imaged with co-registered biopsies or EMR from Sept. 2013 to Nov. 2014. RESULTS: Figure 1 shows representative en face OCT upper GI images. Fig. 1(A) shows normal esophagus with no apparent structure, consistent with the homogeneous appearance of squamous epithelium. Fig. 1(B) shows gastric folds and circular pit patterns, characteristic of normal gastric tissue. Fig. 1(C) shows NDBE and exhibits a cerebriform or gyrus-forming appearance, with pit patterns regularly distributed throughout the region of BE. Figs. 1(D) and 1(E) show low and high grade dysplasia, respectively, and exhibit enlargement and distortion of pit patterns compared to NDBE. Fig. 1(F) shows EAC, where severe distortion of pit pattern is accompanied with abnormally shaped and sized glandular structures. CONCLUSIONS: Ultrahigh speed endoscopic OCT can generate images of mucosal morphology similar to magnification NBI and chromoendoscopy, but over a larger field of view, and with near-microscopic resolution and high contrast. Furthermore, en face OCT images at different depths upto 12mm can be extracted from 3D volumes, which would not be attainable by present confocal endomicroscopy. Moreover, cross-sectional OCT images can be generated that are intrinsically registered to the en face features. En face and cross-sectional OCT promises to improve detection sensitivity of dysplasia in BE over cross-sectional OCT alone, but requires next generation ultrahigh speed OCT technology and scanning probes. ACKNOWLEDGMENT: NIH R01-CA075289-17, R44-CA101067-07, AFOSR FA9550-10-1-0551 and FA9550-121-0499.
MSH1, MSH6 and PMS2) and B-Raf mutation was evaluated. Statistical analysis was performed by using Fisher's exact test and a p value of <0.05 was considered significant. Results: The intensity of ATGL staining was higher in well and moderately differentiated (low grade) CRA (p = 0.0009) as compared to poorly differentiated (high grade) CRA. A unique pattern of clumped basal staining was observed in dysplastic and malignant glands in moderately differentiated CRA (Figure 1). This specific staining pattern was not observed in PDEF although weak PEDF immunostaining was observed in all of the CRA samples. There was no association between ATGL staining intensity and other clinical parameters such as BMI >25 (p = 0.876), angioinvasion (p = 0.561), perineural invasion (p = 0.092), metastasis (p = 1.000) and B-Raf mutation (p = 0.072). Conclusion: Higher ATGL expression is associated with low-grade as compared to high-grade CRA. An ATGL staining pattern unique to low grade CRA may indicate a possible lipolytic process involved in CRA differentiation and this may be helpful in diagnosis in a setting of metastatic adenocarcincinoma with unkown primary. The universally weak PEDF expression in all cases suggests ATGL and PEDF have different roles in CRA.
Su2025
cancer patients with occlusion of the pancreatic duct can be reduced or prevented by PEST. Methods This was a double blind, randomized phase II study. Sixty seven patients with unresectable pancreatic cancer were randomized to receive either enteric coated PEST or placebo. The high dose enteric coated pancreatic enzyme preparation under investigation was 6-9 capsules of pancreatin 457.7mg per day. Patients used two capsules three times daily during main meals and one capsule three times daily during snacks between main meals. The primary endpoint was the percentage change in body weight at eight weeks after the randomization. Results There was no significant difference in the percentage change in body weight between PEST and placebo groups. Patients on pancreatic enzyme lost 1.49% (1.12kg) body weights whereas patients on placebo lost 2.99% (1.63%) (p=0.381). The difference in the percent change of scored Patient-Generated Subjective Global Assessment (PG-SGA) was not significant between two groups (8.85% vs. 15.69%, p=0.18). Subgroup analyses according to the tumor location showed that, in patients with unresectable pancreatic head cancer, the percent change of PG-SGA score was -42.65% in PEST group and 32.93% in placebo group (p=0.0393). Conclusions PEST did not reduce weight loss in unresectable pancreatic cancer patients. However, findings from these results indicate that PEST has the potential to improve nutritional status in patients with unresectable pancreatic head cancer. The effect of PEST on weight loss in patients with pancreatic head cancer should be assessed in a larger randomized trial.
Increased Insulin Resistance Is Not Seen After Recently Diagnosed Colorectal Cancer: A National Health and Nutrition Examination Survey (NHANES) Study Kenneth Obi, Alice Hinton, Razvan Arsenescu, Peter P. Stanich, Darrell M. Gray, Somashekar G. Krishna, Samer El-Dika, Hisham Hussan Background: Increased insulin resistance (IR) was shown to be associated with an increased risk of colorectal cancer (CRC). It is unknown if the onset of CRC impacts insulin resistance after diagnosis. Objective: To determine the association between IR and recently diagnosed CRC in a US representative cohort. Methods: We conducted a cross-sectional study using the National Health and Nutrition Examination Survey (NHANES, 1999 - 2010). IR was determined using the homeostasis model assessment (HOMA-IR) and was classified as the upper quartile of HOMA-IR ( ≥ 3.52) in this study. We excluded participants who were less than age 20, pregnant, on insulin or insulin lowering medications, or who had colorectal cancer diagnosis older than 4 years from the time of survey. Results: There were a total of 88,373,262 patients in our weighted cohort, 24,250,441 (27.4%) of which had IR. Basic demographics were significantly different between patients with and without IR as shown in Table 1. Patients with IR were more likely to consume alcohol and dietary fat but less likely to smoke tobacco (p<0.05). IR was associated with higher Body Mass Index (BMI), Waist Circumference and elevated C-reactive protein (CRP); however patients with IR reported more intentional weight change and a significant drop in their weight over the year prior to the survey (Table 2). There were 148,040 patients with CRC who were equally distributed between the groups with and without IR (P> 0.05). After adjusting for age, race and gender, the prevalence of recently diagnosed CRC remained similar in both groups (OR 1.00, 95% CI 0.48, 2.06). Conclusion: There is no conclusive association between insulin resistance and the prevalence of recently diagnosed colorectal cancer in this US nationally representative cohort of adults. Further prospective studies are required to investigate whether CRC-related weight loss leads to improved insulin resistance in this population and how that can alter risk of subsequent CRC. Table 1
Su2027 Diabetes, Glucose, and Insulin Levels and Risk of Serrated Polyps and Sessile Serrated Adenomas Seth D. Crockett, Christopher F. Martin, John A. Baron, Robert S. Sandler Introduction: Serrated polyps (SPs) such as sessile serrated adenomas (SSAs) have malignant potential, yet their epidemiology is poorly understood. Some studies have suggested that diabetes may be a risk factor for SSAs but data are conflicting. To better elucidate this association, we aimed to determine whether history of diabetes and insulin and glucose levels were related to risk of serrated polyps and SSAs specifically. Methods: Data from a series of cross-sectional studies of patients undergoing colonoscopy at the University of North Carolina between 1998 and 2010 were pooled to identify patients with SPs and conventional adenomas (CAd). Proximal and large SPs were reviewed by an expert pathologist to determine the presence of SSAs. Demographics and risk factor data were collected by standardized interview. Fasting blood samples were obtained at time of colonoscopy for serum glucose and insulin measurements, performed using standard assays. Bivariate analyses were performed using t-tests and chi-squared or Fisher's Exact tests. Multivariate analyses were performed via logistic regression to estimate ORs and 95% CI comparing polyp groups to those with no polyps, while adjusting for age, sex, study, and year of colonoscopy. Results: We identified 1316 (57%) without polyps, 460 with CAd only (20%), 311 with SPs only (13%), and 78 patients with SSAs (3%) among 2308 participants undergoing colonoscopy. A history of diabetes was not significantly associated with either CAd or SPs. Diabetes was present in 11% of patients with SSAs only vs. 9% of patients without polyps (p=0.7). Mean glucose level was higher in patients with CAd compared to those without polyps (132 mg/ dL vs. 125 mg/dL, p=0.03), but this was not true for those with SSAs only (mean glucose 128 mg/dL, p=0.8 vs. no polyp group). Similarly, mean insulin level was higher in patients with CAd compared to those without polyps (10.5 U/mL vs. 8.8 U/mL, p=0.05), but this did not hold for those with SSAs only (mean insulin level 7.4, p=0.6 vs. no polyp group). In multivariate analysis, higher fasting serum glucose and insulin levels were associated with borderline increased risk of CAd [OR 1.04 (95% CI 1.00, 1.08) and OR 1.01 (95% CI 1.00, 1.03), respectively], but not for SPs or SSAs (Table). Further adjustment for body mass index did not substantially alter the results. Conclusions: In this study, we did not find statistically significant associations between diabetes and SPs or SSAs specifically. Elevated glucose and insulin levels were weakly associated with CAd, but there were no associations between glucose and insulin levels and SPs or SSAs. These data suggest that there is not a strong relationship between diabetes and its associated biochemical alterations and serrated pathway neoplasia.
Univariate analysis of participants with and without insulin resistance. Table 2
*OR per 10 unit increase in glucose level Univariate analysis of metabolic markers in participants with and without insulin resistance.
Su2028 Unique Expression of Adipose Triglyceride Lipase (ATGL) in Low Grade Colorectal Carcinoma Vinit V. Patil, Joanne Rutgers, Xianzhong Ding, mona Cornwell, Megan Roth, Nancy Phillips, Carole Vogler, Susan Crawford, Jinping Lai
Su2026 Efficacy of Pancreatic Enzyme Supplementation Therapy in Patients With Unresectable Pancreatic Cancer Sun Seob Park, Sang Myung Woo, So Young Kim, Jungnam Joo, Seung Hyun Chung, Sooin Yun, Sang Jae Park, Sung-Sik Han, Tae Hyun Kim, Young Hwan Koh, Eun Kyung Hong, Woo Jin Lee
Background: Obesity is associated with increased risk of colorectal adenocarcinoma (CRA) and obese individuals have decreased protein expression of adipose triglyceride lipase (ATGL) and pigment epithelium derived factor (PEDF). Additionally, expression of ATGL and PEDF in the tumor microenvironment is associated with cancer growth and spread. Thus, we hypothesize that altered expression of ATGL and PEDF is associated with CRA. Design: Tumor tissue from 56 patients with CRA and clinical information (age, sex, body mass index and cancer case summary) was stained by immunohistochemistry (IHC) for ATGL and PEDF. Intensity of ATGL and PEDF staining, histologic grade, and parameters including BMI >25, lymphovascular and perineural invasion, metastasis, MMR expression (MLH1,
Background Pancreatic cancer is the fifth leading cause of death from cancer in Korea. Weight loss in pancreatic cancer is associated with maldigestion due to pancreatic duct obstruction and pancreatic enzyme supplementation therapy (PEST) may result in a significant improvement in fat and protein absorption. We planned a prospective, randomized, placebo-controlled trial to verify the hypothesis that weight loss in unresectable pancreatic
AGA Abstracts
S-578
Figure 1. ATGL immunoreactivity in a moderately (A) and a poorly (B) differentiated colonic adenocarcinomas (x400). Su2029 In Vivo Imaging of Mucosal Endothelin-a Receptor Expression to Characterize Murine Colorectal Cancer Development Dominik Bettenworth, Marcus Mücke, Christiane Geyer, Carsten Höltke, Katrin Schwegmann, Christopher Poremba, Michael Schäfers, Dirk Domagk, Philipp Lenz
Representative en face OCT images of different upper GI tissues from depths of 100-400um and projected over 80um. A, normal esophagus. B, gastric mucosa. C, Non-dysplastic BE. D, BE with low grade dysplasia. E, BE with high grade dysplasia. F, Esophageal adenocarcinoma (stage T1). Scale bars are 500um.
BACKGROUND AND AIMS: Ulcerative colitis patients are at an increased risk of developing colorectal cancer. Therefore, current guidelines recommend surveillance colonoscopy with chromoendoscopy or random biopsies to detect dyplastic lesions. ET-A receptor (ETAR) expression is known to be significantly increased in various malignancies including colorectal cancer (1). The aim of the study was to detect and characterize early dysplastic lesions in mice by ETAR-guided fluorescence endoscopy (FE) and fluorescence reflectance imaging. METHODS: Colorectal cancer was induced in C57Bl/6 WT mice (n=15) by single injection of azoxymethane i.p. and cyclic administration of dextran sodiumsulfate in drinking water. A Cy5.5-labeled nonpeptidic ETAR imaging probe was intravenously injected 24 hrs before endoscopic examination. Tumor development was assessed in vivo by white light endoscopy and FE. Murine colons were examined by fluorescence reflectance imaging using an MSFX PRO optical imaging system to measure tracer uptake ex vivo. At the end of the experiment, colons were explanted and tumors were graded after HE staining and evaluated by an expert pathologist. Tumor biology was assessed by immunohistochemistry and western blot analysis of ETAR expression. Additionally, binding specificity of the tracer was evaluated by simultaneous injection of an equimolar amount of an unspecific fluorochrome (Cy3.5-glycin) and the specific tracer. RESULTS: ETAR expression could easily be detected by FE and all animals survived the procedure. Standard histology confirmed colorectal adenomas as well as high and low grade dysplasia. Conventional molecular imaging applying the fluorescent ETAR imaging probe showed significantly increased tracer uptake in colorectal adenoma as compared to healthy mucosa (1336.8 ± 375.3 vs. 544.1 ± 90.4, P < 0.001). In contrast, no significant difference in tracer uptake between low and high grade adenoma was found (tumor-to-background ratio: 2.5 ± 0.6 vs. 2.3 ± 0.9, P = 0.637). The tumor-to-background ratio of lesions imaged for Cy3.5 was significantly reduced as compared to Cy5.5 indicating the high binding-specificity of the used ETAR tracer (1.4 ± 0.3 vs. 2.5 ± 0.7, P < 0.001). CONCLUSION: ETAR expression was significantly increased in murine colorectal dysplasia as compared to healthy mucosa. By detection of ETAR via FE in live mice, a prognostic biomarker for colorectal cancer development is directly visualized during colonoscopy, thus facilitating in vivo tumor characterization on a molecular level. (1) Hoosein et al. Altered endothelin receptor subtypes in colorectal cancer. Eur J Gastroenterol Hepatol. 2007
Su2031 Evaluation of Severity Using Endoscopic Dual Red Imaging Targeting Submucosal Vessel in Patients With Ulcerative Colitis Makoto Naganuma, Naohisa Yahagi, Rieko Bessho, Ai Fujimoto, Naoki Hosoe, Kazuhiro Kashiwagi, Tadakazu Hisamatsu, Haruhiko Ogata, Takanori Kanai Background: Endoscopy is useful to assess the severity of inflammation and can predict middle to long term prognosis in patients with ulcerative colitis (UC). Recently, new imaging technology that has three kinds of illumination lights whose center wavelength are 540nm, 600nm and 630nm respectively. The both of lights in 600nm and 630nm are critical to recognize blood vessels in deeper tissue. Because dual red imaging (DRI) can mainly emphasize the findings of vessel pattern, disagreement for assessment the severity of inflammation using DRI might be minimal among the investigators. The aim of this study is to evaluate the additional usefulness of DRI to assess the severity of inflammation in patients with UC. Patients and Methods: A total of 43 UC patients were enrolled to evaluate endoscopic severity at 112 segments of colon using white light imaging and DRI. Two independent investigators assessed and compared between Matts' endoscopic scores and DRI scores (see Figure). Correlation between DRI score and histological grading (Matts histological score 15) was also evaluated. Furthermore, inter-observer agreement for DRI score between two investigators was also assessed. Results: DRI score is closely correlated to Matts'endoscopic (r=0.88) and histological scores (r=0.83). Although rates of DRI score agreement between 2 investigators was 87% (97/112, κ=0.81), rates of Matts endoscopic score agreement was 72% (81/112, κ=0.59). Among patients with mild to moderate colitis (Matts' endoscopic score 2-3). median Matts histological score in patients with DRI score=4 was significantly higher than that in patients with DRI score=2 or 3 (p<0.01). Conclusion: DRI score is closely correlated to former endoscopic and histological score and inter-observer disagreement of DRI was minimal comparing to Matts' score.
Su2030 En Face Optical Coherence Tomography Visualization of Mucosal Surface Patterns for Identifying Early Malignancy in the Upper GI Tract Osman O. Ahsen, Hsiang-Chieh Lee, Kaicheng Liang, Michael G. Giacomelli, Zhao Wang, Marisa Figueiredo, Qin Huang, Benjamin Potsaid, Vijaysekhar Jayaraman, James G. Fujimoto, Hiroshi Mashimo BACKGROUND/AIMS: Aberrant mucosal surface patterns (pit patterns) are associated with dysplasia in Barrett's esophagus (BE). Optical coherence tomography (OCT) can generate volumetric images of tissue microstructure. We have recently demonstrated ultrahigh-speed endoscopic OCT that achieves >10x faster imaging speeds than commercial systems. This OCT, combined with distal micromotor beam scanning, acquires densely sampled volumetric datasets enabling arbitrary cross-sectional and depth-resolved en face OCT images and shows pit patterns with high resolution and contrast. In this study we investigate en face OCT of upper GI tissues including normal squamous epithelium, gastric mucosa, non-dysplastic BE (NDBE), BE with low and high grade dysplasia, as well as esophageal adenocarcinoma (EAC). METHODS: The study was performed at the VABHS under an IRB protocol approved by the VABHS, HMS and MIT. We used an endoscopic OCT system with a 600 kHz axial scan
S-579
AGA Abstracts
AGA Abstracts
rate and 400 fps frame rate. The imaging probe was introduced in the endoscope accessory port for co-registration of images with biopsies. Volumetric datasets were acquired with an 8 second helical scan over a 160mm2 area, and multiple datasets were acquired covering the BE length. A total of 15 BE patients (7 NDBE, 3 LGD, 4 HGD, 1 EAC) were imaged with co-registered biopsies or EMR from Sept. 2013 to Nov. 2014. RESULTS: Figure 1 shows representative en face OCT upper GI images. Fig. 1(A) shows normal esophagus with no apparent structure, consistent with the homogeneous appearance of squamous epithelium. Fig. 1(B) shows gastric folds and circular pit patterns, characteristic of normal gastric tissue. Fig. 1(C) shows NDBE and exhibits a cerebriform or gyrus-forming appearance, with pit patterns regularly distributed throughout the region of BE. Figs. 1(D) and 1(E) show low and high grade dysplasia, respectively, and exhibit enlargement and distortion of pit patterns compared to NDBE. Fig. 1(F) shows EAC, where severe distortion of pit pattern is accompanied with abnormally shaped and sized glandular structures. CONCLUSIONS: Ultrahigh speed endoscopic OCT can generate images of mucosal morphology similar to magnification NBI and chromoendoscopy, but over a larger field of view, and with near-microscopic resolution and high contrast. Furthermore, en face OCT images at different depths upto 12mm can be extracted from 3D volumes, which would not be attainable by present confocal endomicroscopy. Moreover, cross-sectional OCT images can be generated that are intrinsically registered to the en face features. En face and cross-sectional OCT promises to improve detection sensitivity of dysplasia in BE over cross-sectional OCT alone, but requires next generation ultrahigh speed OCT technology and scanning probes. ACKNOWLEDGMENT: NIH R01-CA075289-17, R44-CA101067-07, AFOSR FA9550-10-1-0551 and FA9550-121-0499.
MSH1, MSH6 and PMS2) and B-Raf mutation was evaluated. Statistical analysis was performed by using Fisher's exact test and a p value of <0.05 was considered significant. Results: The intensity of ATGL staining was higher in well and moderately differentiated (low grade) CRA (p = 0.0009) as compared to poorly differentiated (high grade) CRA. A unique pattern of clumped basal staining was observed in dysplastic and malignant glands in moderately differentiated CRA (Figure 1). This specific staining pattern was not observed in PDEF although weak PEDF immunostaining was observed in all of the CRA samples. There was no association between ATGL staining intensity and other clinical parameters such as BMI >25 (p = 0.876), angioinvasion (p = 0.561), perineural invasion (p = 0.092), metastasis (p = 1.000) and B-Raf mutation (p = 0.072). Conclusion: Higher ATGL expression is associated with low-grade as compared to high-grade CRA. An ATGL staining pattern unique to low grade CRA may indicate a possible lipolytic process involved in CRA differentiation and this may be helpful in diagnosis in a setting of metastatic adenocarcincinoma with unkown primary. The universally weak PEDF expression in all cases suggests ATGL and PEDF have different roles in CRA.