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S16 Surgical Forum Abstracts J Am Coll Surg

METHODS: We conducted a retrospective study of 83 consecutivepatients diagnosed with rPA who had a PD at our institution from2001 to 2009. Multivariable analyses were performed using multiplecovariates to determine predictors of survival. We obtained completefollow up until February 2011 in all patients using a populationaldatabase.

RESULTS: Overall median survival was 21 months. The medianurvival for patients with a low symptom score (LS) group was 45onths and it was 17 months in patients with a high symptoms score

HS) group. 24% of LS group patients survived beyond 5 years,ompared to only 12% of HS patients. The overall 5 years survivalas 19%. Although on univariate analysis age, MBS group and mar-in status were significantly associated with survival, in a multivari-ble model (Cox regression), only age [Odds Ratio (OR)�1.03

(95% CI 1-1.06)] and MBS group [OR� 2.46 (95% CI 1.41-4.3)]predicted overall survival. Chemotherapy and tumor size were notassociated with overall survival.

CONCLUSIONS: The MBS is a simple clinically intuitive scorewhich seems to be a better predictor of survival than conventionalpredictors in patients with rPA.

Reduced postoperative recurrence and improved survivalof pancreatic cancer with peritoneal dissemination byinhibition of nuclear factor-kappa B activation in miceYuki Fujiwara MD, Koichiro Haruki MD, Kenei Furukawa MD,Tomonori Iida MD, PhD, Hiroaki Shiba MD, PhD,Tadashi Uwagawa MD, PhD, Takeyuki Misawa MD, PhD,Toya Ohashi MD, PhD, Katsuhiko Yanaga MD, PhDJikei University School of Medicine, Tokyo, Japan

INTRODUCTION: In spite of undergoing curative resection (R0)for the patients with pancreatic cancer, long-term survival is verypoor because of high incidence of cancer recurrence. We previouslyreported that nafamostat mesilate (FUT175), a synthetic serine pro-tease inhibitor inhibits NF-kappa B activation and promotes caspase-8-mediated apoptosis. We herein report inhibition by FUT175 ofcancer cell adhesion, angiogenesis and invasion, which are importantprocesses in peritoneal dissemination, and usefulness of combinationchemotherapy with FUT175 and paclitaxel for peritoneal dissemi-nation of experimental pancreatic cancer.

METHODS: In vitro, we assessed NF-kappaB activity and down-stream target genes of NF-kappa B such as intercellular adhesionmolecule-1 (ICAM-1), interleukin-8 (IL-8), vascular endothelialgrowth factor (VEGF) and matrix metalloproteinase-9 (MMP-9) byFUT175 using human pancreatic cancer cell lines (AsPc-1, BxPc-3,Panc-1). In vivo, we established peritoneal dissemination in nudemice by intra-peritoneal injection of AsPc-1 cells. We assessed ifpre-incubated AsPc-1 with FUT175 reduced peritoneal dissemina-tion and addition of FUT175 to i.p. paclitaxel may enhance anti-tumor effect in peritoneal dissemination of pancreatic cancer in mice.

RESULTS: In vitro, FUT175 inhibited NF-kappa B, ICAM-1,IL-8, VEGF and MMP-9. In vivo, intraperitoneal administration ofAsPc-1 cell incubated with FUT175 reduced peritoneal nodules and

prolonged survival. In combination of FUT175 and i.p. paclitaxel

group, survival rate was significantly better than those in othergroups.

CONCLUSIONS: Pre-operative treatment with FUT175 reducedpostoperative recurrence, and intra-peritoneal combination chemo-therapy using paclitaxel with FUT175 may be a strategy to reduce theincidence of peritoneal dissemination with pancreatic cancer.

Pancreatic stellate cells activate chemokine receptorCCR9 signaling to promote pancreatic cancer cellinvasionWendy Lee BSC, Xiaoming Shen PhD, Maithao N Le MD, PhD,Marjun P Duldulao MD, Jianming Lu BSC,Julio Garcia-Aguilar MD, PhD, FACS,Joseph Kim MD, FACSCity of Hope National Medical Center, Duarte, CA

INTRODUCTION: We previously demonstrated that CCR9 activa-tion by its ligand CCL25 increases pancreatic cancer cell prolifera-tion. We hypothesized that tumor microenvironment cells may be asource for CCL25. Therefore, our objective was to determinewhether tumor microenvironment pancreatic stellate cells (PSCs)contribute to CCR9-mediated pancreatic cancer invasiveness.

METHODS: CCL25 expression in human pancreatic cancer speci-mens was assessed by immunohistochemistry (IHC). For tumor-stroma interactions, we assessed human PSCs and PANC-1 pancre-atic cancer cells under mono- and co-culture conditions. Cellmorphology was analyzed by light microscopy and CCL25 releasewas measured by enzyme linked immunosorbent assay (ELISA). Co-culture supernatant was collected and used in a modified Boydenchamber invasion assay. The CCR9 small molecule inhibitorCCX8037 was used to antagonize CCR9 signaling.

RESULTS: CCL25 expression was detected by IHC in stromal andcancer cells of human pancreatic cancers. Next, PSCs and PANC-1cells were co-cultured without subsequent changes in cell morphol-ogy. Under co-culture conditions, ELISA demonstrated higherCCL25 expression levels compared to PSC and PANC-1 mono-culture (15 and 18%, respectively). In an invasion assay, co-culturesupernatants increased the invasion of PANC-1 cells. The contribu-tion of CCR9 to cell invasion was confirmed by CCX8037, whichinhibited PANC-1 cell invasiveness.

CONCLUSIONS: Our studies demonstrate that human PSCs fromthe tumor microenvironment interact with cancer cells to enhanceCCL25 release. Furthermore, these tumor-stroma interactions maysynergistically activate CCL25-CCR9 signaling to enhance pancre-atic cancer cell invasion; and suggest that targeting the tumor-stromavia CCR9 inhibition may be an effective therapeutic approach.

Adipocytes cause enhanced migration of murinepancreatic cancer cellsPatrick B White MD, Kathryn M Ziegler MD, Sue S Wang MD,Robert V Considine PhD, Deborah A Swartz-Basile PhD,Henry A Pitt MD, FACS, Nicholas J Zyromski MD, FACS

Indiana University School of Medicine, Indianapolis, IN