as the site of the primary lesion moved more distally (% rec. for surgery - duodenum 70% vs. jejunum 90% vs. ileum 93%, p< 0.001). There was no significant difference in mean age at diagnosis, sex, or the number of additional primary cancers between the three primary sites. Using KM methods, five-year survival was marginally better for duodenal and ileal lesions than jejunal lesions (duodenum 67% vs. jejunum 66% vs. ileum 61%, p=0.045). However, on CPH analysis, duodenal lesions had significantly better survival than jejunal or ileal lesions (jejunum vs. duodenum- HR 1.845 [95% CI 1.461-2.329] p<0.001, ileum vs. duodenal - HR 1.665 [95% CI 1.388-1.999], p<0.001), controlling for age, stage, year of diagnosis, sex, race, marital status, and cancer-directed surgery. Conclusion: Epidemiology and survival patterns of SICs vary based on intestinal location. As duodenal lesions are diagnosed at an earlier stage and associated with significantly improved survival than jejunal or ileal lesions, it may be possible to avoid high-risk surgery for selected lesions in these patients. Tu1162 Double Balloon Enteroscopy (DBE) Should Be a Mandatory Tool for Detecting Small Bowel Carcinoids Neel K. Mann, Edward M. Wolin, Steven D. Colquhoun, Nicholas N. Nissen, Deepti Dhall, Run Yu, Laith H. Jamil, Simon K. Lo Background:DBE has been reported as a useful tool for the detection of small bowel carcinoid lesions. However, there are few case reports with small sample sizes in the current literature. Aim: To report our large experience on carcinoid detection with the use of DBE. Method: Retrospective review of all DBE cases in our center. All submucosal small intestinal lesions were identified. Cases with biopsy-proven carcinoids were further examined. Results: 1520 double balloon enteroscopies were performed. In 108 DBEs one or more submucosal small bowel polyps or masses were identified. In 18 of these DBEs, no biopsies were taken. Lesions seen in 6 of these cases were carcinoids based on clinical history or subsequent DBE-directed surgical resections. Of the 90 cases with endoscopic biopsies, 31 (34% of submucosal and 2% of all DBE cases) had histology-validated carcinoids in 30 patients: 20 (65%) cases were discovered by retrograde DBE; 11 by oral DBE. 11 of them were done for the search of a primary small bowel lesion in pts with known liver metastases. 20 cases were done for other reasons: obscure-overt bleed (n=11), obscure-occult bleed (n=2), iron deficiency anemia (n= 3), abdominal pain (n=3), and incidental finding (n=1). 19 biopsy-proven carcinoid pts subsequently underwent surgery. By combining DBE and surgical findings, 16/30 (53%) pts were found to have more than 1 small bowel lesion. The median number of lesions per pt was 2 (range 1-35; mean 4.8, SD 7.0). The median lesion size was 10 mm (mean 10.8 mm, range 1-40 mm). All surgical and endoscopic specimens showed low grade (g1) disease with a low proliferation rate (Ki67 <2%). All patients without a prior carcinoid history had no overt carcinoid symptoms. 9 of these pts had surgical pathology available for review: regional nodal involvement-6, extension to the serosa-1, lesions confined to the submucosa or muscularis propria-2. Additionally, fewer pts had elevated serum or urine tumor markers (4/17; 24%) in this group and yet the location of lesions was essentially the same as those with known metastatic carcinoid (proximal to mid-ileum). Age of presentation for DBE was significantly younger for those undergoing evaluation for metastatic carcinoid than for GI bleeding (56 vs 67, Mann-Whitney 2 tail p<0.02). Conclusions: To our knowledge, this is the largest case series of small bowel carcinoids found by DBE to date. Contrary to common belief, 1/3 of our lesions were discovered on oral DBE and most were found during investi- gations for obscure bleeding. Even though a typical small bowel carcinoid lesion is small (~ 1cm) and is of low histological grade, local-regional metastasis is common at the time of initial diagnosis. A thorough search for both metastasis and multiple luminal lesions and aggressive treatment after deep endoscopic discovery is mandatory. Tu1163 Macroscopic Features of Neuroendocrine Colorectal Cancers: A 10-Year Retrospective Study Chantal le Clercq, Mariëlle Bouwens, Robert Riedl, Bjorn Winkens, Ann Driessen, Wim Hameeteman, Ad Masclee, Silvia Sanduleanu Neuroendocrine colorectal cancers (neCRCs) are uncommon findings during colonoscopic examination. Little is known about the macroscopic appearance of these cancers. We therefore examined the incidence and macroscopic features of neCRCs in our practice. Methods: We reviewed clinicopathologic data of all patients diagnosed with CRC at our university hospital from January 2001 to December 2010. Digital colonoscopy and histopathology records were collected and verified using data from the national pathology database (PALGA) and the Dutch Cancer Registry. Patients with hereditary forms of CRC, inflammatory bowel disease or a previous history of CRC were excluded. neCRCs were defined as cancers located in the colon or rectum and having purely neuroendocrine features, as confirmed by histopatho- logy and immunohistochemistry. We classified all CRCs according to their macroscopic aspect into flat/sessile or protruded. Kaplan-Meier analyses and log-rank test were used to study differences in survival between patients with neCRCs versus adenocarcinomas. Results: We analyzed 1.236 patients with 1.286 CRCs (mean age 70.1 yrs; 55.2% males). In total, 19 (1.5%) patients with neCRCs were found (mean age, 62.9 yrs, range 45-88; 52.6% males). The majority of neCRCs were diagnosed by colonoscopy (n=16), 2 during autopsy and 1 during surgery for acute bowel obstruction. Seventy-four % of the neCRCs were located in the rectosigmoid. Mean size of neCRCs was 2.1 (range, 0.2-6.8) cm, with 53% of them being smaller than 1 cm. Forty-seven percent of the neCRCs had a flat/sessile macroscopic appearance. Logistic regression analyses, adjusting for age and gender showed that neCRCs were significantly smaller in size (OR 0.45, 95%CI 0.31-0.66, p<0.001) and had more often a flat/sessile macroscopic appearance (OR 3.0, 95%CI 1.1-7.9, p=0.028) than colorectal adenocarcinomas. In 10 cases, neCRCs were associated with synchronous colorectal lesions, namely adenocarcinoma (1), adenomatous polyps (5) or hyperplastic polyps (4). Five (26%) patients with neCRCs had metastasized disease at the time of diagnosis and deceased within six months, while the remaining patients are still alive. Mean survival of patients with neCRCs was 32 months and did not significantly differ from that of patients with adenocarcinomas. Conclusion: In this study, neuroendocrine CRCs accounted for 1.5% of all CRCs detected and the majority of them appeared to have a small size and flat/ S-763 AGA Abstracts sessile macroscopic appearance. Characterization of macroscopic features of neuroendocrine CRCs may be of importance for improving their endoscopic recognition. Tu1164 Specific SRC Family Kinases (SFK) Mediate EGF Receptor Transactivation by Gastrointestinal Hormones of a Foregut Net Tumor Livia Archibugi, Alessia Di Florio, Samuel A. Mantey, Gianfranco Delle Fave, Robert T. Jensen Background: Although most foregut Neuroendocrine Tumors [F-NETs] (carcinoids, pancre- atic endocrine tumors) are relatively slowing tumors, there is an increasing number that show aggressive behavior. Current therapies for advanced F-NETs are inadequate. SFKs are overexpressed in F-NETs and studies have shown they play a central role in controlling cell growth, adhesion and migration. In some cells, Src kinases play a key role in the ability of gastrointestinal (GI) hormones to transactivate the EGF receptor (EGFR) and cause growth. These are 9 members of the SFK and it is unclear which are generally present in F- NETs or mediate cellular changes. Aim: To elucidate the role of SFKs in mediating EGFR transactivation in F-NETs by GI hormones. Methods: Five F-NET cells were used, a human pancreatic carcinoid (BON), a human somatostatinoma (QGP-1), 2 rat insulinomas (Rin-m, Rin-mF) and a rat somatostatinoma (Rin-14B). EGFR transactivation was assessed by assessing pY1068 EGFR. SFK activation was assessed by measuring the Y416 phosphorylation and specific SFK activation after specific immunoprecipitation. Results: Antibodies specific for the SFKs isoforms Src, Lyn, Yes, Fyn and Lck were identified using standards. Western blotting using cell lysates from each of the 5 foregut NETs (BON, QGP-1, Rin-m, Rin-mF and Rin-14B) demonstrated they only express the SFKs Src, Yes, Lyn. To understand their role in EGFR transactivation by GI hormones, the BON cell was studied. A number of GI hormones/GF stimulated growth of BON cells, which was inhibited by an EGFR antagonist. Assessment of pY1068 EGFR by Western blotting, demonstrated increased phosphorylation stimulated by TGFα (3.6 nM), neurotensin (NT) (1 μΜ), PACAP (1 μM) and a bombesin- related agonist (Bn-analogue, 1 μM). Stimulation of pY1068 EGFR by GI hormones, but not TGFα, was inhibited by PP2, a SFKs inhibitor, but not by its inactive analogue, PP3. In cell lysates we found that all the GI hormones were able to activate SFKs by stimulating the pY416 SFKs. To understand which of the Src kinases expressed in BON cells was involved in the EGFR transactivation mediating cell growth, we performed immunoprecipitation experiments using specific antibodies for Src, Yes and Lyn isoforms, from BON cells stimulated with NT, or PACAP, or the Bn-Analogue and assessed, by Western blotting, the pY416 SFKs. NT activated both Src and Yes SFKs isoforms. Conclusions: Foregut NETs possess multiple SFKs, particularly Src, Yes, Lyn. In BON cells the transactivation of EGFR by GI hormones that stimulates proliferation is by activating SFKs. Our results support the conclu- sion that the different SFKs are differentially involved in the EGFR transactivation. Tu1165 An Acute Shower of Circulating Tumour Cells Following Transarterial Embolisation (TAE) Mohid S. Khan, Christina Thirlwell, Christos Toumpanakis, Martyn Caplin, Tim Meyer Introduction: Shedding of tumour cells following transarterial-embolisation (TAE) in NETs has not previously been demonstrated. Aim: We have analysed changes in circulating tumour cells (CTCs) and Cell Free DNA (cfDNA) in patients with Neuroendocrine Tumours (NETs) undergoing TAE for hepatic metastasis Methods: Twelve patients were studied. Blood was analysed for CTCs and cfDNA at baseline and post-procedure on days 1, 2, 3, 4 and week 6. CTCs were enumerated using the CellSearch system as previously described. cfDNA was extracted from plasma using a Qiagen mini-kit (Qiagen,UK) and quantified with a High Sensitivity Chip on an Agilent Bioanalyser 2100. As a control, 5 additional patients with metastatic NETs had samples taken before and after PRRT (2),surgery (2), RFA (1). Results: 10/12 undergoing TAE had CTCs at baseline (range 0-147). All 12 had an increase in CTCs at day 1 post-TAE (median increase 695% over baseline, range 156-3100%). Increases in cfDNA corresponded to CTC increases but lagged by one day. No patient undergoing other treatments had any increase in CTCs. After a median FU of 4 months, 3 patients have died (OS 2.5, 1.9, 0.6 months), 2 of which had the smallest post-TAE CTC increases (by 5 and 7 respectively). CTCs recovered to below baseline in all but 2/12 patients (these 2 patients died). Conclusion: We demonstrate an acute ‘shower' of CTCs and cfDNA following TAE. Better survival following TAE may be predicted by a reduction of CTCs below baseline but further follow-up in a larger cohort of patients is required. Tu1166 Salinomycin Enhances Imatinib Effects in Murine Interstitial Cell of Cajal (ICC) Stem Cells and Gastrointestinal Stromal Tumor (GIST) Cells and Inhibits Glycosylation of Kit Protein While Triggering Expression of Truncated Intracellular Kit Yujiro Hayashi, Simon J. Gibbons, Michael R. Bardsley, Takahiro Taguchi, Gianrico Farrugia, Brian P. Rubin, Tamas Ordog Background & Aims: Inhibitors of Kit signaling, such as imatinib mesylate (IM), are the mainstay of treatment for advanced GIST but are not curative. We reported that transformed Kit low ICC stem cells (ICC-SC) represent an IM-resistant pool for GIST but can be instead inhibited with the epithelial cancer stem cell-targeting antibiotic salinomycin (Sal). Sal also enhanced the weak inhibitory effect of IM on ICC-SC proliferation. Sal in therapeutic doses is predicted to be toxic. Therefore, we tested whether low doses of Sal can also increase the efficacy of IM and investigated the underlying mechanisms. As epithelial cancer stem cells have mesenchymal characteristics, we also tested whether Sal can inhibit more differentiated GIST cells. Methods: We studied the IM-resistant murine ICC-SC lines D2211B and 2xSCS2F10, as well as the Kit-mutant human GIST lines GIST-T1 (Kit + , IM-sensitive) and GIST48B (Kit low , IM-resistant; lacks wild-type (wt) Kit). Cell proliferation was quantified by methyltetrazolium assay. Gene expression and post-translational modifications were AGA Abstracts