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703 Prospective Trial of PillCam Colon Capsule (CCE) vs CT-Colonography (CTC) in the Evaluation of Patients With Incomplete Conventional Colonoscopy (CC): an Interim Analysis
Abstracts
702 Development of a New Classification for Confocal LASER Endomicroscopy in IBD Helmut Neumann*1, Emmanuel Coron2, Klaus MöNkemüLler3, Markus F. Neurath1, Michael Vieth4 1 Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany; 2Centre Hospitalier Universitaire, Nantes, France; 3 Basil Hirschowitz Endoscopic Center of Excellence, University of Alabama at Birmingham, Birmingham, AL; 4Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany
704 In Vivo Molecular Imaging and Assessment of Therapeutic Response of Colorectal Cancer Targeting Epidermal Growth Factor Receptor Naoki Muguruma*, Yoshihiko Miyamoto, Koichi Okamoto, Shinji Kitamura, Tadahiko Nakagawa, Tohshi Takaoka, Miho Tsuda, Rie Harada, Tetsu Tomonari, Hiroshi Miyamoto, Toshiya Okahisa, Tetsuji Takayama Department of Gastroenterology and Oncology, The University of Tokushima Graduate School, Tokushima, Japan
Introduction: Probe-based confocal laser endomicroscopy (pCLE) allows in vivo on demand histology during ongoing colonoscopy and has the potential to analyze mucosal and submucosal alterations in real time. Here, an international collaboration of five experts proposed a new and unique pCLE classification for the use in patients with inflammatory bowel disease (IBD). Aims: Main study objective was to establish a pCLE classification for IBD. Second study objective was to assess accuracy, interobserver and intraobserver agreement of the new classification. Material & Methods: Consecutive patients with known IBD underwent screening or surveillance colonoscopy and were evaluated using pCLE. First, a post hoc review of 25 pCLE video sequences was performed in order to accomplish a new classification system based on different vessel and crypt categories. Accordingly, all observers scored an additional set of 100 pCLE video sequences, using the new classification. In all cases, histopathological analysis served as the reference standard. Results: Based on different vessel and crypt categories a new pCLE classification for IBD was developed. The interobserver agreements for vessel and crypt architecture were substantial with kappa values of 0.7737 (95% confidence interval: 0.6475-0.8999) and 0.6311 (95% confidence interval: 0.4776-0.7846), respectively. Intraobserver agreements for vessel and crypt architecture were substantial with kappa values of 0.7541 (95% confidence interval: 0.4931-1) and 0.6753 (95% confidence interval: 0.3837-0.9669), respectively. Overall, sensitivity, specificity and accuracy for predicting histological inflammation in macroscopically uninflamed mucosa were 94%, 81%, and 87%, respectively. Positive and negative predictive values were 82% and 94%, respectively. Conclusion: A new and unique classification for pCLE in IBD was developed and validated by a panel of international experts. The classification allows prediction of microscopic inflammation in macroscopically non-inflamed mucosa. Final results will be reported at DDW.
Background/Aim: The epidermal growth factor receptor (EGFR) which participates in signaling pathways commonly appears on colorectal cancer. Cetuximab is a chimerical IgG2 monoclonal antibody that binds to EGFR and blocks ligand-induced phosphorylation of EGFR. Given that EGFR serves as a biomarker of response to EGFR-directed therapies, noninvasive assessment for indicating and predicting therapeutic response to antibody is required to establish the individualized selection of therapy. The aim of this study is to evaluate optical molecular imaging methods as correlative biomarkers of therapeutic efficacy of cetuximab in human colorectal cancer cell line and xenografts grown in nude mice. Methods: Five colorectal cancer cell lines were used. The number of cell surface EGFR was quantified by flow cytometeric analysis using FITC-labeled anti-EGFR antibody. Each cell line was incubated with Alexa Fluor-labeled anti-EGFR-antibody (sc-120 AF488, SANTA CRUZ BIOTECHNOLOGY, INC.) with and without fixation. After rinsing with PBS, each cell line was observed by confocal laser microscopy (Leica TCS NT) and bench top fluorescence microscopy (BZ 9000, KEYENCE), then the fluorescent signal intensity was calculated. Subcutaneous tumors were induced by injection 107 cells in the groin of female Balb/c nu/nu mice and imaging was performed after 4 weeks when tumor size approximated 10 mm. Alexa Fluor labeled anti-EGFR antibody was injected into the tail vein of the mice under general anesthesia using 2% isoflurane. Cetuximab was conjugated to indocyanine green (ICG: Dojindo Laboratories) and this labeled antibody was also injected to the xenografts. In vivo images were recorded with IVIS Spectrum imaging system (Caliper Life Sciences). Results: The numbers of EGFR (count/cell) were quantified as follows: 45,000 in M7609, 23,000 in HT-29, 21,600 in CoCM-1, 12,800 in DLD-1 and 8 in COLO320DM. The fluorescent intensities were 29.3 in COLO320DM, 42.3 in DLD-1, 50.0 in CoCM-1, 61.3 in HT-29 and 67.7 in M7609. There was a significant correlation between the number of EGFR and fluorescent intensity. When Alexa Fluor labeled anti-EGFR-antibody was injected into nude mice bearing M7609 xenografted tumor, the strong and specific fluorescence was detected at the tumor after 24 hours. It also demonstrated excellent fluorescence 72 hours after injection of ICG-cetuximab, which showed the different biodistribution from that with Alexa Fluor anti-EGFR antibody. Conclusion: Fluorescence image reflected the characteristics of EGFR expression in cell lines. In vivo molecular imaging of colorectal cancer is feasible in xenografted nude mice with both diagnostic and therapeutic markers targeting EGFR. Fluorescence- labeled antibody is a promising agent for differentiating EGFR-overexpressing tumors, and could help evaluating the efficacy during endoscopic molecular imaging.
703 Prospective Trial of PillCam Colon Capsule (CCE) vs CTColonography (CTC) in the Evaluation of Patients With Incomplete Conventional Colonoscopy (CC): an Interim Analysis Cristiano Spada*1, Cesare Hassan1, Paola Cesaro1, Brunella Barbaro2, Franco Iafrate3, Lucio Petruzziello1, Leonardo Minelli1, Marcella Iannitti3, Marco Salsano2, Giuseppe Alvaro2, Maria Elena Riccioni1, Riccardo Marmo1, Andrea Laghi3, Lorenzo Bonomo2, Guido Costamagna1 1 Digestive Endoscopy Unit, Catholic University, Rome, Italy; 2 Radiology, Catholic University, Rome, Italy; 3Radiology, La Sapienza University, Rome, Italy Introduction: CC may be incomplete in 4-25% of pts. In such cases, complementary tests (CTC, barium enema, colonoscopy using different endoscopes or with anaesthesiology assistance) are indicated to complete colonic inspection. Recently, CCE (PillCam Colon, Given Imaging, Israel) was shown to be feasible to complement incomplete CC. Aims & Methods: To compare CCE and CTC in terms of completeness and accuracy in pts with incomplete CC. This is an interim analysis of a prospective, blinded trial in which CCE was compared to CTC in pts with incomplete CC. Pts underwent CCE and CTC on the same day, following the standard regimen of preparation for CCE with the inclusion of sodium-amidotrizoate and meglumineamidotrizoate (75 ml) (Gastrografin, Bayer, Italy) after the boosters. CTC was performed after CCE excretion or, latest, 10-12 hours post ingestion. CCE and CTC were defined complete when they visualized colonic segments not explored by CC. To evaluate the incremental value of CCE and CTC, the efficacy analysis was performed considering significant findings (polyps/masses ⱖ6mm) in segments not visualized during the first CC. In case of significant findings and/or discrepancies a second CC (gold standard) was performed. Bowel preparation and adverse events (AE) were assessed. Results: 50 pts (19M, mean age 57yrs) completed the study between 09/2011 and 04/2012 out of 100 patients planned. One pt refused CTC because of air insufflation and was excluded from the efficacy analysis. CCE and CTC were complete in 98% and 96% of cases, respectively. 7 pts had at least one ⱖ6mm polyp at CCE. In 1 pt, a ⱖ6mm polyp was detected both by CCE and CTC, and confirmed by second CC. Six pts had polyps ⱖ6mm detected by CCE only: polyps were confirmed by second CC in 5 pts. One pt had a ⱖ6mm polyp detected by CTC only: polyp was not visualized by CCE nor found during the second CC. Difference in CCE and CTC diagnostic yield was not significant (p⫽0.18). CCE cleansing level was adequate in 78% of cases. CTC procedure was adequate in 80% of cases. No severe AE were reported. Conclusion: Preliminary results suggest that both, CCE and CTC, are effective to complete incomplete CC, but CCE tends to detect more polyps than CTC in segments not visualized by incomplete CC.
705 Restoring Tactile Perception in Natural Orifice Transluminal Endoscopic Surgery (NOTES) Through Wireless Tissue Palpation Marco Beccani*1, Christian Di Natali1, Pietro Valdastri1, Keith L. Obstein2,1 1 Mechanical Engineering, Vanderbilt University, Nashville, TN; 2 Medicine, Vanderbilt University Medical Center, Nashville, TN Background: Natural Orifice Transluminal Endoscopic Surgery (NOTES) has steadily advanced from laboratory experiments to human clinical trials. Unlike open surgery, the physician has few chances to leverage tactile and kinesthetic feedback. We have developed a novel system for wireless tissue palpation to overcome this obstacle. Aim: To assess a novel wireless tissue palpation system for tactile and kinesthetic feedback. Methods: The novel system was tested on three different silicone based tissue phantoms (elastic modulus range: 50 kPa to 93 kPa). The system consists of a wireless palpation cylinder (12.7 mm diameter ⫻ 27.5 mm height) that is deployed through the NOTES access site and is coupled with an external robotic manipulator. The robotic manipulator holds a load cell and a permanent magnet. Embedded within the wireless palpation cylinder are a magnetic field sensor, a wireless microcontroller, a LiPo battery, an accelerometer, and a permanent magnet. A total of 5 trials were performed for each phantom. The operator first palpated each phantom with the dominant index finger, qualitatively assessing for a difference in stiffness. The phantoms were then palpated by the operator using the novel palpation system. For each trial, the indentation depth and the exerted force were measured, thus providing the local elastic module as a quantitative measure of the sample stiffness. The accelerometer, used as an inclinometer, confirmed that the motion was always occurring on the vertical axis. A cylindrical indenter, the same size as the wireless palpation cylinder, was then mounted on the robotic manipulator and adopted as a reference measurement system to assess the measured elastic modulus. Results: The novel wireless tissue palpation system achieved a precision 96.87% in reconstructing the achieved indentation depth, based on magnetic field measurements, with an accuracy of 0.15 mm ( ⫽ 0.12mm). Experimental trials demonstrated the effectiveness of wireless vertical indentation in
AB163 GASTROINTESTINAL ENDOSCOPY Volume 77, No. 5S : 2013
www.giejournal.org
702 Development of a New Classification for Confocal LASER Endomicroscopy in IBD Helmut Neumann*1, Emmanuel Coron2, Klaus MöNkemüLler3, Markus F. Neurath1, Michael Vieth4 1 Department of Medicine 1, University of Erlangen-Nuremberg, Erlangen, Germany; 2Centre Hospitalier Universitaire, Nantes, France; 3 Basil Hirschowitz Endoscopic Center of Excellence, University of Alabama at Birmingham, Birmingham, AL; 4Institute of Pathology, Klinikum Bayreuth, Bayreuth, Germany
704 In Vivo Molecular Imaging and Assessment of Therapeutic Response of Colorectal Cancer Targeting Epidermal Growth Factor Receptor Naoki Muguruma*, Yoshihiko Miyamoto, Koichi Okamoto, Shinji Kitamura, Tadahiko Nakagawa, Tohshi Takaoka, Miho Tsuda, Rie Harada, Tetsu Tomonari, Hiroshi Miyamoto, Toshiya Okahisa, Tetsuji Takayama Department of Gastroenterology and Oncology, The University of Tokushima Graduate School, Tokushima, Japan
Introduction: Probe-based confocal laser endomicroscopy (pCLE) allows in vivo on demand histology during ongoing colonoscopy and has the potential to analyze mucosal and submucosal alterations in real time. Here, an international collaboration of five experts proposed a new and unique pCLE classification for the use in patients with inflammatory bowel disease (IBD). Aims: Main study objective was to establish a pCLE classification for IBD. Second study objective was to assess accuracy, interobserver and intraobserver agreement of the new classification. Material & Methods: Consecutive patients with known IBD underwent screening or surveillance colonoscopy and were evaluated using pCLE. First, a post hoc review of 25 pCLE video sequences was performed in order to accomplish a new classification system based on different vessel and crypt categories. Accordingly, all observers scored an additional set of 100 pCLE video sequences, using the new classification. In all cases, histopathological analysis served as the reference standard. Results: Based on different vessel and crypt categories a new pCLE classification for IBD was developed. The interobserver agreements for vessel and crypt architecture were substantial with kappa values of 0.7737 (95% confidence interval: 0.6475-0.8999) and 0.6311 (95% confidence interval: 0.4776-0.7846), respectively. Intraobserver agreements for vessel and crypt architecture were substantial with kappa values of 0.7541 (95% confidence interval: 0.4931-1) and 0.6753 (95% confidence interval: 0.3837-0.9669), respectively. Overall, sensitivity, specificity and accuracy for predicting histological inflammation in macroscopically uninflamed mucosa were 94%, 81%, and 87%, respectively. Positive and negative predictive values were 82% and 94%, respectively. Conclusion: A new and unique classification for pCLE in IBD was developed and validated by a panel of international experts. The classification allows prediction of microscopic inflammation in macroscopically non-inflamed mucosa. Final results will be reported at DDW.
Background/Aim: The epidermal growth factor receptor (EGFR) which participates in signaling pathways commonly appears on colorectal cancer. Cetuximab is a chimerical IgG2 monoclonal antibody that binds to EGFR and blocks ligand-induced phosphorylation of EGFR. Given that EGFR serves as a biomarker of response to EGFR-directed therapies, noninvasive assessment for indicating and predicting therapeutic response to antibody is required to establish the individualized selection of therapy. The aim of this study is to evaluate optical molecular imaging methods as correlative biomarkers of therapeutic efficacy of cetuximab in human colorectal cancer cell line and xenografts grown in nude mice. Methods: Five colorectal cancer cell lines were used. The number of cell surface EGFR was quantified by flow cytometeric analysis using FITC-labeled anti-EGFR antibody. Each cell line was incubated with Alexa Fluor-labeled anti-EGFR-antibody (sc-120 AF488, SANTA CRUZ BIOTECHNOLOGY, INC.) with and without fixation. After rinsing with PBS, each cell line was observed by confocal laser microscopy (Leica TCS NT) and bench top fluorescence microscopy (BZ 9000, KEYENCE), then the fluorescent signal intensity was calculated. Subcutaneous tumors were induced by injection 107 cells in the groin of female Balb/c nu/nu mice and imaging was performed after 4 weeks when tumor size approximated 10 mm. Alexa Fluor labeled anti-EGFR antibody was injected into the tail vein of the mice under general anesthesia using 2% isoflurane. Cetuximab was conjugated to indocyanine green (ICG: Dojindo Laboratories) and this labeled antibody was also injected to the xenografts. In vivo images were recorded with IVIS Spectrum imaging system (Caliper Life Sciences). Results: The numbers of EGFR (count/cell) were quantified as follows: 45,000 in M7609, 23,000 in HT-29, 21,600 in CoCM-1, 12,800 in DLD-1 and 8 in COLO320DM. The fluorescent intensities were 29.3 in COLO320DM, 42.3 in DLD-1, 50.0 in CoCM-1, 61.3 in HT-29 and 67.7 in M7609. There was a significant correlation between the number of EGFR and fluorescent intensity. When Alexa Fluor labeled anti-EGFR-antibody was injected into nude mice bearing M7609 xenografted tumor, the strong and specific fluorescence was detected at the tumor after 24 hours. It also demonstrated excellent fluorescence 72 hours after injection of ICG-cetuximab, which showed the different biodistribution from that with Alexa Fluor anti-EGFR antibody. Conclusion: Fluorescence image reflected the characteristics of EGFR expression in cell lines. In vivo molecular imaging of colorectal cancer is feasible in xenografted nude mice with both diagnostic and therapeutic markers targeting EGFR. Fluorescence- labeled antibody is a promising agent for differentiating EGFR-overexpressing tumors, and could help evaluating the efficacy during endoscopic molecular imaging.
703 Prospective Trial of PillCam Colon Capsule (CCE) vs CTColonography (CTC) in the Evaluation of Patients With Incomplete Conventional Colonoscopy (CC): an Interim Analysis Cristiano Spada*1, Cesare Hassan1, Paola Cesaro1, Brunella Barbaro2, Franco Iafrate3, Lucio Petruzziello1, Leonardo Minelli1, Marcella Iannitti3, Marco Salsano2, Giuseppe Alvaro2, Maria Elena Riccioni1, Riccardo Marmo1, Andrea Laghi3, Lorenzo Bonomo2, Guido Costamagna1 1 Digestive Endoscopy Unit, Catholic University, Rome, Italy; 2 Radiology, Catholic University, Rome, Italy; 3Radiology, La Sapienza University, Rome, Italy Introduction: CC may be incomplete in 4-25% of pts. In such cases, complementary tests (CTC, barium enema, colonoscopy using different endoscopes or with anaesthesiology assistance) are indicated to complete colonic inspection. Recently, CCE (PillCam Colon, Given Imaging, Israel) was shown to be feasible to complement incomplete CC. Aims & Methods: To compare CCE and CTC in terms of completeness and accuracy in pts with incomplete CC. This is an interim analysis of a prospective, blinded trial in which CCE was compared to CTC in pts with incomplete CC. Pts underwent CCE and CTC on the same day, following the standard regimen of preparation for CCE with the inclusion of sodium-amidotrizoate and meglumineamidotrizoate (75 ml) (Gastrografin, Bayer, Italy) after the boosters. CTC was performed after CCE excretion or, latest, 10-12 hours post ingestion. CCE and CTC were defined complete when they visualized colonic segments not explored by CC. To evaluate the incremental value of CCE and CTC, the efficacy analysis was performed considering significant findings (polyps/masses ⱖ6mm) in segments not visualized during the first CC. In case of significant findings and/or discrepancies a second CC (gold standard) was performed. Bowel preparation and adverse events (AE) were assessed. Results: 50 pts (19M, mean age 57yrs) completed the study between 09/2011 and 04/2012 out of 100 patients planned. One pt refused CTC because of air insufflation and was excluded from the efficacy analysis. CCE and CTC were complete in 98% and 96% of cases, respectively. 7 pts had at least one ⱖ6mm polyp at CCE. In 1 pt, a ⱖ6mm polyp was detected both by CCE and CTC, and confirmed by second CC. Six pts had polyps ⱖ6mm detected by CCE only: polyps were confirmed by second CC in 5 pts. One pt had a ⱖ6mm polyp detected by CTC only: polyp was not visualized by CCE nor found during the second CC. Difference in CCE and CTC diagnostic yield was not significant (p⫽0.18). CCE cleansing level was adequate in 78% of cases. CTC procedure was adequate in 80% of cases. No severe AE were reported. Conclusion: Preliminary results suggest that both, CCE and CTC, are effective to complete incomplete CC, but CCE tends to detect more polyps than CTC in segments not visualized by incomplete CC.
705 Restoring Tactile Perception in Natural Orifice Transluminal Endoscopic Surgery (NOTES) Through Wireless Tissue Palpation Marco Beccani*1, Christian Di Natali1, Pietro Valdastri1, Keith L. Obstein2,1 1 Mechanical Engineering, Vanderbilt University, Nashville, TN; 2 Medicine, Vanderbilt University Medical Center, Nashville, TN Background: Natural Orifice Transluminal Endoscopic Surgery (NOTES) has steadily advanced from laboratory experiments to human clinical trials. Unlike open surgery, the physician has few chances to leverage tactile and kinesthetic feedback. We have developed a novel system for wireless tissue palpation to overcome this obstacle. Aim: To assess a novel wireless tissue palpation system for tactile and kinesthetic feedback. Methods: The novel system was tested on three different silicone based tissue phantoms (elastic modulus range: 50 kPa to 93 kPa). The system consists of a wireless palpation cylinder (12.7 mm diameter ⫻ 27.5 mm height) that is deployed through the NOTES access site and is coupled with an external robotic manipulator. The robotic manipulator holds a load cell and a permanent magnet. Embedded within the wireless palpation cylinder are a magnetic field sensor, a wireless microcontroller, a LiPo battery, an accelerometer, and a permanent magnet. A total of 5 trials were performed for each phantom. The operator first palpated each phantom with the dominant index finger, qualitatively assessing for a difference in stiffness. The phantoms were then palpated by the operator using the novel palpation system. For each trial, the indentation depth and the exerted force were measured, thus providing the local elastic module as a quantitative measure of the sample stiffness. The accelerometer, used as an inclinometer, confirmed that the motion was always occurring on the vertical axis. A cylindrical indenter, the same size as the wireless palpation cylinder, was then mounted on the robotic manipulator and adopted as a reference measurement system to assess the measured elastic modulus. Results: The novel wireless tissue palpation system achieved a precision 96.87% in reconstructing the achieved indentation depth, based on magnetic field measurements, with an accuracy of 0.15 mm ( ⫽ 0.12mm). Experimental trials demonstrated the effectiveness of wireless vertical indentation in
AB163 GASTROINTESTINAL ENDOSCOPY Volume 77, No. 5S : 2013
www.giejournal.org