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T1215 Development of a Breath Test for the Evaluation of the Postprandial Gastric Accommodation Process
stains nuclei, was applied topically to fresh surgical resections. Two systems were used to image; a multispectral microscope (WF resolution: 50-100μm) and a probe-based microendoscope (HR: 4-7μm). Proflavine excites at 450 nm and emits at 510 nm; corresponding filter sets were used. Images were compared to histopathologic gold-standard read by a GI pathologist. Results: WF fluorescence imaging of proflavine enhanced visualization of architecture, such as glandular distortion and crowding associated with neoplastic progression. WF differences were further evaluated with HR imaging: neoplastic progression was associated with glandular heterogeneity and disorganization and nuclear crowding. In the esophagus - normal squamous, intestinal metaplasia and cancer were observed. In the colon - normal columnar, dysplasia, and cancer were observed (example shown in Fig. 1). Abnormalities visible on WF images correlated to glandular and nuclear changes seen in HR images as well as pathology. Conclusions: Imaging using topical proflavine shows promise in delineating the epithelial features of neoplasia. Enhanced glandular features seen using WF imaging can guide HR probe placement for microscopic imaging and correlation with standard histopathologic features. This preliminary work suggests that fluorescent endoscopic imaging using a single dye provides a useful ‘bridge' between standard endoscopy and ‘optical biopsy' techniques. In Vivo evaluation is underway.
T1214 Clinical Significance of Incidental Gastrointestinal FDG Uptake Found on PET/PET-CT Scans During Staging of Multiple Myeloma Somashekar G. Krishna, Shyam M. Dang, Brian T. Hughes, Dhaval H. Patel, Farshad Aduli Background: 2-(F)-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography-computed tomography (PET-CT) scans are non-invasive imaging modalities used to detect and follow malignant tumors. FDG uptake is also seen in non-malignant process like granulomatous lesions, infective or inflammatory lesions, and physiologic sites with increased metabolism. Purpose: To evaluate the endoscopic and pathological findings of incidental gastrointestinal tract (GIT) FDG uptake on PET and PET-CT during staging of patients with multiple myeloma. Methods: We conducted a retrospective review of PET and PET-CT scans for staging of patients with multiple myeloma (January 2004 - December 2006). The incidence of scans showing incidental GIT uptake, corresponding intensity [standard uptake value (SUV) based on lean body mass] and location was determined. The results of all endoscopic procedures and histopathological findings were reviewed. Results: A total of 729 PET and PET-CT scans results were reviewed. Endoscopy was performed to verify FDG uptake in 46 patients; endoscopic abnormalities were noted in 24 patients (52%), 18 of whom (39%) had biopsy proven disease. Lower gut diagnoses included tubular and/or tubulovillous adenoma (7 patients, SUV 5-17); plasmacytomas (SUV 10-14), adenocarcinoma (SUV ~7) and colitis (diffuse uptake), 2 patients each. Four patients had diverticulosis only (SUV 24). Upper gut involvement included esophagitis (3 patients, SUV 2-3), and gastric plasmacytoma (SUV 13.6), hiatal hernia (SUV 3.9) and Zenker's diverticulum (SUV 4.2), one patient each. The SUV for abnormal endoscopic findings ranged from of 2 to 17 (n = 13, mean = 7.485) compared to normal endoscopic findings, range of 4-15 (n = 17, mean = 6.812); p-value of 0.657. Conclusion: Among a homogenous population of patients with multiple myeloma, incidental focal FDG uptake localized by PET or PET-CT within the GIT appears to have clinical significance. Because intensity of FDG uptake was not predictive of histology, endoscopic workup is warranted in such patients.
T1217 Endomicroscopy Can Readily Identify In Vivo Dysfunctional Cell Shedding and Local Barrier Dysfunction in the Upper GI-Tract of Patients With Crohn's Disease Lee Guan Lim, Janina Patricia Neumann, Martin Goetz, Arthur Hoffman, Markus F. Neurath, Peter R. Galle, Alastair J. Watson, Ralf Kiesslich Introduction: Increased epithelial cell shedding and epithelial gaps formation might play a crucial role in the intestinal barrier dysfunction of patients with Crohn's disease (CD). An initial study from our group reported an increased number of epithelial gaps within the macroscopically unaffected terminal ileum in CD which could only be identified using confocal laser endomicroscopy (Pentax, Japan). The aim of the study was to clarify whether increased gap formation is a local (terminal ileum) or systemic (involvement of the upper GI-tract) phenomenon. Primary outcome analysis was the total number of gaps within unaffected gastric or duodenal mucosa.. Methods: Patients with known history of Crohn's disease and matched controls were recruited. Upper endoscopy with fluorescein aided endomicroscopy (systemic application - 5ml; 10%) was performed and the mucosa of the antrum and duodenum were endomicroscopically imaged from the lumen to the lamina propria [z-stacks]. From each z-stack, 3 images with the most epithelial gaps were selected for interpretation. Total epithelial gaps (TEG) were the sum of confluent epithelial gaps (more than one cell-size width) and isolated epithelial gaps (one cell width). The amount of cell shedding was graded from 0 (none) to 8 (maximum). Luminal signal was graded from 1 (black) to 6 (total white). Brighter luminal signal would imply leakage of fluorescein across epithelial gaps into the intestinal lumen and hence be a measure of local barrier function. Results: 6 patients with Crohn's disease and 4 controls were recruited. Patients with CD showed significant higher amount of gaps, cell shedding and luminal signal compared to controls (see table). Conclusion: Confocal laser endomicroscopy is the only imaging tool which enables the diagnosis of local barrier dysfunction and epithelial gap formation. Patient with Crohn's disease without macroscopically affected upper GI-tract unequivocally showed endomicroscopically an increased amount of cell shedding, gaps and luminal fluorescein leakage in the duodenum compared to normal controls. These findings imply that dysfunctional cell shedding is a systemic phenomenon of the small bowel and may play an important role in the pathogenesis of Crohn's disease.
T1215 Development of a Breath Test for the Evaluation of the Postprandial Gastric Accommodation Process Rafael Tojo, Laura Nieto, Enrique Dominguez-Munoz Background: Gastric accommodation (GA) process provides a gastric reservoir allowing the ingestion of a meal without increasing intragastric pressure or inducing postprandial symptoms. GA is adapted to the properties of the meal and contributes to a correct gastric emptying of nutrients for a normal digestion process. Alteration of GA is accepted as a major pathogenetic factor in functional dyspepsia. Methods to evaluate GA are invasive, nonphysiological or inaccurate. Aim: To design a non-invasive, physiological method to evaluate GA based on the 13C-acetate breath test for gastric emptying of liquids. This GA breath test is based on the hypothesis that two liquid meals of different volumes and the same caloric load are emptied from the stomach at the same rate due to the GA process. Subjects and methods: An experimental, open label, crossover study on 14 healthy volunteers (7 men and 7 women, aged 20 - 25 years, mean age 22.6 + 0.8 years) was performed. Gastric emptying of four different liquid test meals containing 300Kcal each, and a volume of 200, 400, 600 and 800 mL, respectively, was measured by the 13C-acetate breath test at four different days one-week apart. Breath samples were collected at 15min intervals for 180min, and analyzed by mass spectrometry. The half gastric emptying time (t1/2) for each test meal was calculated and compared by ANOVA and Bonferroni test. Results: Gastric t1/2 was the same for meals of 200, 400 and 600mL (68.4+11.0min, 64.5+8.4min, and 66.2+8.3min, respectively). On the contrary, 800mL meals were emptied at a faster rate (t1/2=54.9+7.2min, p<0.05). Conclusions: The difference in gastric emptying rate (t1/2) of two meals of 600 and 200mL as measured by 13C-acetate breath test is an adequate method to evaluate gastric accommodation. In healthy subjects this difference is close to zero due to a normal GA. A meal with a volume of 800mL exceeds the physiological GA capacity. T1216 Vital Dye Enhanced Fluorescence Imaging of Esophageal and Colorectal Neoplasia Nadhi Thekkek, Timothy J. Muldoon, Alexandros D. Polydorides, Noam Harpaz, Dipen Maru, Sharmila Anandasabapathy, Rebecca Richards-Kortum
T1218 Detection of Aberrant Crypt Foci in Patients at High-Risk for Colorectal Cancer Using Confocal Laser Endomicroscopy Sanne Gulikers, Eveline Rondagh, Ann Driessen, Ad Masclee, Silvia Sanduleanu
Current endoscopic surveillance is limited in its ability to sample entire at-risk epithelium. High-resolution (HR) modalities such as confocal endomicroscopy afford an ‘optical biopsy' of epithelium, however these technologies image a small area (< 1mm). ‘Red flag' imaging of large surface areas is needed to identify mucosal changes warranting ‘optical biopsy.' The objective of this ex vivo study was to evaluate the feasibility of using widefield (WF) and HR fluorescence imaging with vital dye contrast to improve endoscopic evaluation in subjects with gastrointestinal (GI) neoplasia. Methods: Proflavine (0.01%), a fluorescent dye that
Aberrant crypt foci (ACF) are considered putative precursors of neoplastic lesions and might represent an early biomarker for colonic carcinogenesis. Previous studies in humans using high-magnification chromoendoscopy showed large heterogeneity in the prevalence of ACF, resulting from technical difficulties in the histological confirmation. Confocal laser endomicroscopy (CLE) is a rapidly emerging endoscopy technique, which provides In Vivo
S-513
AGA Abstracts
AGA Abstracts
burning depth. In post-CSA patients, edema over a 650 μm depth range caused by freezing was observed. Compared to RFA, CSA appeared to cause less overall architecture distortion in the tissue. Endoscopic OCT enables 3D real-time analysis over a large area of the treated site, potentially allowing assessment of treatment effectiveness using different ablation technologies. The correlation of these architectural changes to actual tissue destruction will be further investigated. CONCLUSIONS: While endoscopic 3D-OCT does not possess the same magnification or contrast as conventional histopathologic analysis, it is capable of visualizing large and deeper tissue volumes In Vivo. RFA demonstrates greater tissue architectural changes, but CSA shows treatment effects in deeper tissue structures. The ability to detect tissue structural changes following different ablation therapies makes 3D-OCT an ideal tool to assess the treated regions, help identify areas for retreatment, and guide refinements in treatment dosing.
T1214 Clinical Significance of Incidental Gastrointestinal FDG Uptake Found on PET/PET-CT Scans During Staging of Multiple Myeloma Somashekar G. Krishna, Shyam M. Dang, Brian T. Hughes, Dhaval H. Patel, Farshad Aduli Background: 2-(F)-fluoro-2-deoxy-D-glucose (FDG) positron emission tomography-computed tomography (PET-CT) scans are non-invasive imaging modalities used to detect and follow malignant tumors. FDG uptake is also seen in non-malignant process like granulomatous lesions, infective or inflammatory lesions, and physiologic sites with increased metabolism. Purpose: To evaluate the endoscopic and pathological findings of incidental gastrointestinal tract (GIT) FDG uptake on PET and PET-CT during staging of patients with multiple myeloma. Methods: We conducted a retrospective review of PET and PET-CT scans for staging of patients with multiple myeloma (January 2004 - December 2006). The incidence of scans showing incidental GIT uptake, corresponding intensity [standard uptake value (SUV) based on lean body mass] and location was determined. The results of all endoscopic procedures and histopathological findings were reviewed. Results: A total of 729 PET and PET-CT scans results were reviewed. Endoscopy was performed to verify FDG uptake in 46 patients; endoscopic abnormalities were noted in 24 patients (52%), 18 of whom (39%) had biopsy proven disease. Lower gut diagnoses included tubular and/or tubulovillous adenoma (7 patients, SUV 5-17); plasmacytomas (SUV 10-14), adenocarcinoma (SUV ~7) and colitis (diffuse uptake), 2 patients each. Four patients had diverticulosis only (SUV 24). Upper gut involvement included esophagitis (3 patients, SUV 2-3), and gastric plasmacytoma (SUV 13.6), hiatal hernia (SUV 3.9) and Zenker's diverticulum (SUV 4.2), one patient each. The SUV for abnormal endoscopic findings ranged from of 2 to 17 (n = 13, mean = 7.485) compared to normal endoscopic findings, range of 4-15 (n = 17, mean = 6.812); p-value of 0.657. Conclusion: Among a homogenous population of patients with multiple myeloma, incidental focal FDG uptake localized by PET or PET-CT within the GIT appears to have clinical significance. Because intensity of FDG uptake was not predictive of histology, endoscopic workup is warranted in such patients.
T1217 Endomicroscopy Can Readily Identify In Vivo Dysfunctional Cell Shedding and Local Barrier Dysfunction in the Upper GI-Tract of Patients With Crohn's Disease Lee Guan Lim, Janina Patricia Neumann, Martin Goetz, Arthur Hoffman, Markus F. Neurath, Peter R. Galle, Alastair J. Watson, Ralf Kiesslich Introduction: Increased epithelial cell shedding and epithelial gaps formation might play a crucial role in the intestinal barrier dysfunction of patients with Crohn's disease (CD). An initial study from our group reported an increased number of epithelial gaps within the macroscopically unaffected terminal ileum in CD which could only be identified using confocal laser endomicroscopy (Pentax, Japan). The aim of the study was to clarify whether increased gap formation is a local (terminal ileum) or systemic (involvement of the upper GI-tract) phenomenon. Primary outcome analysis was the total number of gaps within unaffected gastric or duodenal mucosa.. Methods: Patients with known history of Crohn's disease and matched controls were recruited. Upper endoscopy with fluorescein aided endomicroscopy (systemic application - 5ml; 10%) was performed and the mucosa of the antrum and duodenum were endomicroscopically imaged from the lumen to the lamina propria [z-stacks]. From each z-stack, 3 images with the most epithelial gaps were selected for interpretation. Total epithelial gaps (TEG) were the sum of confluent epithelial gaps (more than one cell-size width) and isolated epithelial gaps (one cell width). The amount of cell shedding was graded from 0 (none) to 8 (maximum). Luminal signal was graded from 1 (black) to 6 (total white). Brighter luminal signal would imply leakage of fluorescein across epithelial gaps into the intestinal lumen and hence be a measure of local barrier function. Results: 6 patients with Crohn's disease and 4 controls were recruited. Patients with CD showed significant higher amount of gaps, cell shedding and luminal signal compared to controls (see table). Conclusion: Confocal laser endomicroscopy is the only imaging tool which enables the diagnosis of local barrier dysfunction and epithelial gap formation. Patient with Crohn's disease without macroscopically affected upper GI-tract unequivocally showed endomicroscopically an increased amount of cell shedding, gaps and luminal fluorescein leakage in the duodenum compared to normal controls. These findings imply that dysfunctional cell shedding is a systemic phenomenon of the small bowel and may play an important role in the pathogenesis of Crohn's disease.
T1215 Development of a Breath Test for the Evaluation of the Postprandial Gastric Accommodation Process Rafael Tojo, Laura Nieto, Enrique Dominguez-Munoz Background: Gastric accommodation (GA) process provides a gastric reservoir allowing the ingestion of a meal without increasing intragastric pressure or inducing postprandial symptoms. GA is adapted to the properties of the meal and contributes to a correct gastric emptying of nutrients for a normal digestion process. Alteration of GA is accepted as a major pathogenetic factor in functional dyspepsia. Methods to evaluate GA are invasive, nonphysiological or inaccurate. Aim: To design a non-invasive, physiological method to evaluate GA based on the 13C-acetate breath test for gastric emptying of liquids. This GA breath test is based on the hypothesis that two liquid meals of different volumes and the same caloric load are emptied from the stomach at the same rate due to the GA process. Subjects and methods: An experimental, open label, crossover study on 14 healthy volunteers (7 men and 7 women, aged 20 - 25 years, mean age 22.6 + 0.8 years) was performed. Gastric emptying of four different liquid test meals containing 300Kcal each, and a volume of 200, 400, 600 and 800 mL, respectively, was measured by the 13C-acetate breath test at four different days one-week apart. Breath samples were collected at 15min intervals for 180min, and analyzed by mass spectrometry. The half gastric emptying time (t1/2) for each test meal was calculated and compared by ANOVA and Bonferroni test. Results: Gastric t1/2 was the same for meals of 200, 400 and 600mL (68.4+11.0min, 64.5+8.4min, and 66.2+8.3min, respectively). On the contrary, 800mL meals were emptied at a faster rate (t1/2=54.9+7.2min, p<0.05). Conclusions: The difference in gastric emptying rate (t1/2) of two meals of 600 and 200mL as measured by 13C-acetate breath test is an adequate method to evaluate gastric accommodation. In healthy subjects this difference is close to zero due to a normal GA. A meal with a volume of 800mL exceeds the physiological GA capacity. T1216 Vital Dye Enhanced Fluorescence Imaging of Esophageal and Colorectal Neoplasia Nadhi Thekkek, Timothy J. Muldoon, Alexandros D. Polydorides, Noam Harpaz, Dipen Maru, Sharmila Anandasabapathy, Rebecca Richards-Kortum
T1218 Detection of Aberrant Crypt Foci in Patients at High-Risk for Colorectal Cancer Using Confocal Laser Endomicroscopy Sanne Gulikers, Eveline Rondagh, Ann Driessen, Ad Masclee, Silvia Sanduleanu
Current endoscopic surveillance is limited in its ability to sample entire at-risk epithelium. High-resolution (HR) modalities such as confocal endomicroscopy afford an ‘optical biopsy' of epithelium, however these technologies image a small area (< 1mm). ‘Red flag' imaging of large surface areas is needed to identify mucosal changes warranting ‘optical biopsy.' The objective of this ex vivo study was to evaluate the feasibility of using widefield (WF) and HR fluorescence imaging with vital dye contrast to improve endoscopic evaluation in subjects with gastrointestinal (GI) neoplasia. Methods: Proflavine (0.01%), a fluorescent dye that
Aberrant crypt foci (ACF) are considered putative precursors of neoplastic lesions and might represent an early biomarker for colonic carcinogenesis. Previous studies in humans using high-magnification chromoendoscopy showed large heterogeneity in the prevalence of ACF, resulting from technical difficulties in the histological confirmation. Confocal laser endomicroscopy (CLE) is a rapidly emerging endoscopy technique, which provides In Vivo
S-513
AGA Abstracts
AGA Abstracts
burning depth. In post-CSA patients, edema over a 650 μm depth range caused by freezing was observed. Compared to RFA, CSA appeared to cause less overall architecture distortion in the tissue. Endoscopic OCT enables 3D real-time analysis over a large area of the treated site, potentially allowing assessment of treatment effectiveness using different ablation technologies. The correlation of these architectural changes to actual tissue destruction will be further investigated. CONCLUSIONS: While endoscopic 3D-OCT does not possess the same magnification or contrast as conventional histopathologic analysis, it is capable of visualizing large and deeper tissue volumes In Vivo. RFA demonstrates greater tissue architectural changes, but CSA shows treatment effects in deeper tissue structures. The ability to detect tissue structural changes following different ablation therapies makes 3D-OCT an ideal tool to assess the treated regions, help identify areas for retreatment, and guide refinements in treatment dosing.