Vadim Kurbatov

Abstract 2070: Gemcitabine-loaded microparticles promote cancer cell death in subcutaneous pancreatic cancer xenografts

Pancreatic cancer is the fourth leading cause of cancer death in the United States with only 7% of diagnosed patients surviving 5 years. Most pancreatic cancer patients are not surgical candidates due to advanced stage at diagnosis. Current systemic chemotherapies, while exposing patients to the adverse side effects of treatment, have not been very effective at decreasing tumor burden primarily due to poor systemic drug uptake resulting from the dense stromal nature of pancreatic tumors. Poly(lactic-co-glycolic acid)-based (PLGA) microparticles (MPs) are a promising tool for localized drug delivery within the tumor due to their high biocompatibility, flexibility in the encapsulation of different drugs and extended drug release inside the tumor. The present study investigated whether gemcitabine-loaded microparticles (GMPs) in the range of 10-50 microns, in comparison with blank (no drug) MPs (BMPs), saline intraperitoneal injection (SIP) and gemcitabine intraperitoneal injection (GIP) as controls, are able to promote cancer cell killing effects in vivo. In vitro studies with PANC-1 and MIAPaCa-2 human pancreatic adenocarcinoma cell lines treated with different PLGA co-polymer ratios used to encapsulate gemcitabine showed enhanced cell killing and decreased colony formation in the longer release co-polymer ratio after 2 weeks of treatment. Subsequently, the in vivo efficacy of GMPs was tested by direct injection of GMPs into established subcutaneous MIAPaCa-2 tumors in nude mice. Treatment commenced when tumor volume was approximately 250 mm3. Following two weeks of treatment, there was a trending decrease in tumor volume in the GMPs-injected MIAPaCa-2 tumors compared to the BMPs-injected tumors. When comparing the SIP to GIP groups, there was no difference in final tumor volume emphasizing the lack of effective penetration of systemic gemcitabine into the tumor. In addition, we observed less tumor progression in the GMPs group compared to the others. At the endpoint, the tumors were excised, frozen in OCT compound and sectioned to visualize fluorescent MPs and to detect apoptosis by immunofluorescence. Interestingly, we observed a significant increase in apoptosis in the tumors treated with GMPs compared to the BMP tumors (p In conclusion, our data suggest that gemcitabine-loaded MPs could decrease tumor volume and increase local pancreatic tumor cell death. Further studies are needed to optimize the MPs loading and injection to confirm its efficacy. The described drug delivery method has the potential to be a more efficient local treatment modality than systemic gemcitabine against pancreatic cancer. Citation Format: Maria Munoz-Sagastibelza, Vadim Kurbatov, Sophia Dynes, Jennifer Caceres, Michael Chen, Raavi Gupta, Catherine Burkhart, Laura Martello-Rooney. Gemcitabine-loaded microparticles promote cancer cell death in subcutaneous pancreatic cancer xenografts. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2070.

A rare case of splenic pseudoaneurysm in pediatric splenic blunt trauma patient: Review of diagnosis and management.

Highlights • Splenic pseudoaneurysms (SPA) are a rare but serious sequela of blunt splenic trauma.• Natural course and management of SPA are not well defined in children.• We report a case of splenic pseudoaneurysm in pediatric blunt trauma.• CTA showed underestimate of severity of SPA compared to direct catheter angiography.• We propose an algorithm of management for pediatric splenic trauma.

Abstract B33: Classification of pancreatic cysts in a minority population through cytokine profiling of cyst fluid fine-needle aspirate

Pancreatic cyst detection rate has increased due to the widespread use of cross-sectional imaging. Pancreatic cysts can be divided pathologically into pseudocysts, non-neoplastic cysts such as serous cystadenomas, and pancreatic cystic neoplasms. Malignant potential is seen in pancreatic cystic neoplasms, particularly mucinous cystic neoplasms and intraductal papillary mucinous neoplasms. Proper identification of mucinous cysts warrants either continual surveillance or evaluation for surgical resection to prevent potential development of pancreatic adenocarcinoma. Large urban medical centers, serving a predominantly minority population with an increased incidence of pancreatic cancer, require accurate and prompt diagnosis of malignant cysts. Currently, the standard cyst fluid analyses include CEA, amylase and cytology. In many cases these are of limited value and new biomarkers need to be defined to assist in accurate designation of cyst type. Previous studies have used proteomic analyses to improve cyst identification. One candidate set of protein markers are cytokines, which are involved in cell-mediated responses. A subset of cytokines has been implicated in the carcinogenic process. We hypothesized that the cytokine concentration in the pancreatic cyst fluid obtained via endoscopic ultrasound fine-needle aspiration will be differentially detected and could be used as an additional test to differentiate mucinous cystadenomas and cystadenocarcinomas from pseudocysts and serous cystoadenomas. The study protocol was designed to determine the pancreatic cyst fluid cytokine levels between mucinous and nonmucinous pancreatic cysts using a slide-based quantitative multiplex cytokine antibody array (Raybiotech, Norcross, GA). The cytokine array allowed for the quantitative detection of 20 cytokines with the parallel measurement of individual cytokine standard curves. Initial screening of 18 samples (8 mucinous, 10 nonmucinous) demonstrated differential detection of multiple cytokine targets, such as IL-1α and IL-5 that were statistically significant (P Citation Format: Rajesh Ramachandran, Larry Siu, Vadim Kurbatov, Evan Grossman, Frank Gress, Laura Martello. Classification of pancreatic cysts in a minority population through cytokine profiling of cyst fluid fine-needle aspirate. [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Innovations in Research and Treatment; May 18-21, 2014; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2015;75(13 Suppl):Abstract nr B33.