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1030 Oncolytic Adenovirus Expressing a Dual-Function Gene for Imaging and Treatment of Pancreatic Cancer
performed for weight regain from 2004-2008 were retrospectively compared with consecutive ES procedures from 2008-2011. Patients were only included if ≥1 follow-up weight was available. Patients were censored at time of relapse to preprocedural weight or second procedure (EGBR only). Means were compared using Student's t-test and proportions were compared using Fisher's Exact test. All statistics are reported as mean ± SEM. Results: 128 patients underwent 165 EGBR procedures (1.29 ±0.06 per patient). 206 patients underwent 469 ES procedures (2.28 ±0.07 per patient). Baseline characteristics are reported in Table 1. EGBR patients had significantly lower preprocedure BMI, larger preprocedure GJA, and underwent significantly fewer procedures (all p<0.01). After EGBR, 64.1% of patients were below baseline weight or had avoided a second procedure at 12 months; 46.9% at 24 months; 39.8% at 36 months; and 34.3% at 60 months. During follow-up of EGBR (674 ±63 days), 32.8% of patients had success. Weight loss after EGBR was 8.0 ±4.6 lbs, or 9.0 ±2.6% of excess weight (0.74 ±0.3% EWL/month). After ES, 86.9% of patients were below baseline weight or had avoided a second procedure at 12 months; 68.9% at 24 months; and 65.5% at 36 months (p<0.01 vs EGBR at each timepoint). During follow-up of ES (464 ±19 days), 67.5% of patients had success (p<0.01 vs EGBR). Weight loss after ES was 8.0 ±1.9 lbs, or 13.0 ±8.4 % of excess weight (1.0 ±0.4% EWL/month); these were not significantly different from EGBR. The Kaplan-Meier curve for maintenance of weight loss is shown in Figure 1. Conclusions: Patients undergoing ES for weight regain were more likely to maintain success during long-term follow-up than patients undergoing EGBR, although the magnitude of weight loss was similar. Longer-term study of ES will be beneficial to determine whether there is a plateau for weight maintenance rate. Table 1: Baseline characteristics
*p<0.05 1030 Oncolytic Adenovirus Expressing a Dual-Function Gene for Imaging and Treatment of Pancreatic Cancer Julia Davydova, Miguel Trujillo, Michael J. Oneal, Samantha J. McDonough, Stephen R. Nelson, Joohee Han, John C. Morris, Selwyn M. Vickers, Masato Yamamoto
2D virtual OPT section through a colorectal polyp.
The natural expression of sodium-iodide symporter (NIS) in the thyroid has been successfully exploited as a way to achieve non-invasive imaging and radiotherapy of benign thyroid disease and thyroid cancer for more than 50 years. This therapy has proven to be safe and effective, even in advanced metastatic disease. In this research, we propose to overexpress NIS in pancreatic tumors with a Conditionally-Replicative Adenovirus (CRAd) for combined imaging and treatment of pancreatic cancer. We hypothesized that combined delivery of diagnostic and therapeutic agents will offer a great potential to optimize disease management by avoiding non-therapeutic surgery while optimally treating pancreatic cancer. Fusion of functional (SPECT) and high resolution anatomical (CT) data detecting selective adenovirusmediated NIS expression may give more sensitivity and specificity than other existing imaging modalities. First, we developed non-selective NIS expressing vectors and evaluated their In Vitro cytocidal effect in pancreatic cancer cell lines known to cause aggressive peritoneal dissemination. We observed high oncolytic potential of our vectors and confirmed the significant benefit of 5/3 modification and adenoviral death protein (ADP) overexpression in killing S2VP10, S2013, AsPC1 and MiaPaca2 pancreatic cancer cells. To study In Vivo NIS-based imaging and the effect of combination therapy with 131I, we established A549 subcutaneous tumors in nude mice. Oncolytic Ad-treated mice showed significantly improved radiotracer uptake than mice injected with a replication-defective Ad-NIS. Quantitative analysis of the images confirmed that the NIS-mediated 99mTcO4- accumulation with a replication-competent Ad5/3-ADP-NIS increased with time as signals peaked 5-18 days post treatment compared to 1-4 days with a non-replicative Ad5/3-NIS. Importantly, survival rate was greatly improved when it was combined with 131I. These data confirmed the efficient In Vivo NIS expression from the oncolytic adenovirus and feasibility of combination of enhanced adenovirus efficacy with radiotherapy. Next, we propagated and analyzed the 5/3 fiber-modified Cox2 promoter-selective vectors with the NIS transgene. Cox2 promoter was active in established pancreatic cancer cells and human pancreatic cancer specimens while exhibiting low activity in normal tissues including liver, the organ of most concern involving ectopic Ad gene expression. In Vitro, our new CRAds could successfully drive virus replication in pancreatic cancer cells without hampering its selectivity and produce NIS uptake. Radioiodine uptake was shown to be time- and dose-dependent. Thus, our work provides proof-of-concept that by combining CRAd's enhanced antitumor effect with radiotherapy and NIS-based imaging we can create a new generation of theranostics to diagnose and treat pancreatic cancer.
1029
1031
Long-Term Effectiveness of Sclerotherapy Versus Endoscopic Sutured Gastric Bypass Repair for Management of Weight Regain Due to Dilated Gastrojejunal Anastomosis Nitin Kumar, Marvin Ryou, Barham K. Abu Dayyeh, Pichamol Jirapinyo, David B. Lautz, Christopher C. Thompson
A Novel Kumc Gastric Closure Device for Natural Orifice Transluminal Endoscopic Surgery: In Vitro Comparison of Gastric Closure Modalities Hyuk Soon Choi, Hoon Jai Chun, Bora Keum, Yong Sik Kim, Yoon Tae Jeen, Hong Sik Lee, Chang Duck Kim, Yoonjin Kim, Byunggon Kim, Kyungnam Kim, Youngnam Song, Daehie Hong
Background: Weight regain after Roux-en-Y gastric bypass (RYGB) is correlated with dilated gastrojejunal anastomosis (GJA). Endoscopic sutured gastric bypass repair (EGBR) and sclerotherapy (ES) via endoscopic injection of sodium morrhuate around the GJA are two methods to reduce GJA diameter. Aim: To analyze the long-term effectiveness of these procedures for therapy of weight regain in patients post-RYGB. Methods: Consecutive EGBR procedures
Background Recently gastrointestinal endoscopy and minimally invasive surgery have created the new concept of natural orifice transluminal endoscopic surgery (NOTES). The success of NOTES depends on reliable, secure closure of the gastrostomy. The authors developed a novel device to continuously close a viscerotomy of stomach. (KUMC model III) The aim of this study was to compare strength of various gastrotomy closure techniques in a porcine
3D OPT image of a colorectal polyp.
S-179
AGA Abstracts
AGA Abstracts
population in the UK. Specimens were embedded in agarose gel and optically cleared before being scanned using OPT. 2D and 3D images were used to obtain qualitative diagnostic information and results were compared to standard Haematoxylin & Eosin (H&E) stained sections. RESULTS: 352 polyps were examined from 175 patients (70.5% male; median age 62 years). Surface morphology was clearly identifiable by OPT and comparable with H&E diagnoses: tubular (23.3%), tubulovillous (75.0%) or villous (1.7%). Low-grade dysplasia (59.7%) was distinguishable from high-grade dysplasia (25.3%) and invasive cancer (15.0%) using OPT but differentiation between the latter two was less distinct. However, OPT demonstrated additional features (e.g. surface ulceration, epithelial misplacement and vasculature patterns) that were not present on examined H&E sections. CONCLUSION: This is the first study to use OPT to visualise colorectal polyps and its ability to render 3D images and scroll through virtual sections sets OPT apart from other technologies in the field. We have identified features of colonic polyps which are not always present on standard 2D H&E sections. OPT may prove useful in guiding diagnoses of colonic polypoid cancers but requires further validation as a robust diagnostic tool.
*p<0.05 1030 Oncolytic Adenovirus Expressing a Dual-Function Gene for Imaging and Treatment of Pancreatic Cancer Julia Davydova, Miguel Trujillo, Michael J. Oneal, Samantha J. McDonough, Stephen R. Nelson, Joohee Han, John C. Morris, Selwyn M. Vickers, Masato Yamamoto
2D virtual OPT section through a colorectal polyp.
The natural expression of sodium-iodide symporter (NIS) in the thyroid has been successfully exploited as a way to achieve non-invasive imaging and radiotherapy of benign thyroid disease and thyroid cancer for more than 50 years. This therapy has proven to be safe and effective, even in advanced metastatic disease. In this research, we propose to overexpress NIS in pancreatic tumors with a Conditionally-Replicative Adenovirus (CRAd) for combined imaging and treatment of pancreatic cancer. We hypothesized that combined delivery of diagnostic and therapeutic agents will offer a great potential to optimize disease management by avoiding non-therapeutic surgery while optimally treating pancreatic cancer. Fusion of functional (SPECT) and high resolution anatomical (CT) data detecting selective adenovirusmediated NIS expression may give more sensitivity and specificity than other existing imaging modalities. First, we developed non-selective NIS expressing vectors and evaluated their In Vitro cytocidal effect in pancreatic cancer cell lines known to cause aggressive peritoneal dissemination. We observed high oncolytic potential of our vectors and confirmed the significant benefit of 5/3 modification and adenoviral death protein (ADP) overexpression in killing S2VP10, S2013, AsPC1 and MiaPaca2 pancreatic cancer cells. To study In Vivo NIS-based imaging and the effect of combination therapy with 131I, we established A549 subcutaneous tumors in nude mice. Oncolytic Ad-treated mice showed significantly improved radiotracer uptake than mice injected with a replication-defective Ad-NIS. Quantitative analysis of the images confirmed that the NIS-mediated 99mTcO4- accumulation with a replication-competent Ad5/3-ADP-NIS increased with time as signals peaked 5-18 days post treatment compared to 1-4 days with a non-replicative Ad5/3-NIS. Importantly, survival rate was greatly improved when it was combined with 131I. These data confirmed the efficient In Vivo NIS expression from the oncolytic adenovirus and feasibility of combination of enhanced adenovirus efficacy with radiotherapy. Next, we propagated and analyzed the 5/3 fiber-modified Cox2 promoter-selective vectors with the NIS transgene. Cox2 promoter was active in established pancreatic cancer cells and human pancreatic cancer specimens while exhibiting low activity in normal tissues including liver, the organ of most concern involving ectopic Ad gene expression. In Vitro, our new CRAds could successfully drive virus replication in pancreatic cancer cells without hampering its selectivity and produce NIS uptake. Radioiodine uptake was shown to be time- and dose-dependent. Thus, our work provides proof-of-concept that by combining CRAd's enhanced antitumor effect with radiotherapy and NIS-based imaging we can create a new generation of theranostics to diagnose and treat pancreatic cancer.
1029
1031
Long-Term Effectiveness of Sclerotherapy Versus Endoscopic Sutured Gastric Bypass Repair for Management of Weight Regain Due to Dilated Gastrojejunal Anastomosis Nitin Kumar, Marvin Ryou, Barham K. Abu Dayyeh, Pichamol Jirapinyo, David B. Lautz, Christopher C. Thompson
A Novel Kumc Gastric Closure Device for Natural Orifice Transluminal Endoscopic Surgery: In Vitro Comparison of Gastric Closure Modalities Hyuk Soon Choi, Hoon Jai Chun, Bora Keum, Yong Sik Kim, Yoon Tae Jeen, Hong Sik Lee, Chang Duck Kim, Yoonjin Kim, Byunggon Kim, Kyungnam Kim, Youngnam Song, Daehie Hong
Background: Weight regain after Roux-en-Y gastric bypass (RYGB) is correlated with dilated gastrojejunal anastomosis (GJA). Endoscopic sutured gastric bypass repair (EGBR) and sclerotherapy (ES) via endoscopic injection of sodium morrhuate around the GJA are two methods to reduce GJA diameter. Aim: To analyze the long-term effectiveness of these procedures for therapy of weight regain in patients post-RYGB. Methods: Consecutive EGBR procedures
Background Recently gastrointestinal endoscopy and minimally invasive surgery have created the new concept of natural orifice transluminal endoscopic surgery (NOTES). The success of NOTES depends on reliable, secure closure of the gastrostomy. The authors developed a novel device to continuously close a viscerotomy of stomach. (KUMC model III) The aim of this study was to compare strength of various gastrotomy closure techniques in a porcine
3D OPT image of a colorectal polyp.
S-179
AGA Abstracts
AGA Abstracts
population in the UK. Specimens were embedded in agarose gel and optically cleared before being scanned using OPT. 2D and 3D images were used to obtain qualitative diagnostic information and results were compared to standard Haematoxylin & Eosin (H&E) stained sections. RESULTS: 352 polyps were examined from 175 patients (70.5% male; median age 62 years). Surface morphology was clearly identifiable by OPT and comparable with H&E diagnoses: tubular (23.3%), tubulovillous (75.0%) or villous (1.7%). Low-grade dysplasia (59.7%) was distinguishable from high-grade dysplasia (25.3%) and invasive cancer (15.0%) using OPT but differentiation between the latter two was less distinct. However, OPT demonstrated additional features (e.g. surface ulceration, epithelial misplacement and vasculature patterns) that were not present on examined H&E sections. CONCLUSION: This is the first study to use OPT to visualise colorectal polyps and its ability to render 3D images and scroll through virtual sections sets OPT apart from other technologies in the field. We have identified features of colonic polyps which are not always present on standard 2D H&E sections. OPT may prove useful in guiding diagnoses of colonic polypoid cancers but requires further validation as a robust diagnostic tool.