International Conference on Pancreatic Disorders and Treatment October 17-19, 2016 Chicago, Illinois, USA

Biography:

Enqiang Linghu is the Director of Department of Gastroenterology and Hepatology of China PLA General Hospital. In 2004, he further studied in Endoscopy Center of Massachusetts General Hospital and got his MD degree in 2008. He is successor President of Chinese Society of Digestive Endoscopy (CSDE), Director of Gastroesophageal Varices Academical Group of CSGE and successor President of Beijing Medical Society of Digestive Endoscopy. He is a famous Expert of Digestive Endoscopy domestically and internationally, especially good at ERCP, EUS diagnosis and treatment for pancreatic cystic lesions and digestive endoscopic tunnel techniques (POEM, STER and ESTD).

Abstract:

Background: With the development of imaging techniques, pancreatic cystic lesions are becoming more and more prevalent. Classification of pancreatic cysts lesions which is closely correlated with treatment is pretty complicated, but it is difficult to define the nature of cysts by imaging alone, and surgical morbidity and mortality rates are high. A proper diagnostic approach with high sensitivity and specificity and a kind of safe operation with minimally invasive are urgently needed. Now, there are a few reports about the optimal values for Chinese people to differentiate the pancreatic cystic lesions with large population and EUS-guided lauromacrogol ablation has not been reported.

Methods: From April 2015 to May 2016, 120 patients of small pancreatic cystic neoplasms were prospectively enrolled to perform EUS, among whom 59 patients finally received surgery while 29 patients underwent EUS-guided ablation with lauromacrogol and 7 of them underwent the second ablation so there are 36 cases of ablation. Diagnostic effect of EUS was evaluated with pathology as gold standard. The follow-up pancreatic enhanced CT or MRI was taken at 3 months and then 6 months after ablation. We determined the efficiency of ablation by RECIST criteria.

Results: Among 58 patients with EUS, 9 patients were diagnosed to be malignant by surgical pathology. The sensitivity and

specificity of EUS in differentiating benign from malignant cysts was 93.9% (46/49) and 100% (9/9) and the accuracy is 94.8% (55/58). EUS-FNA cyst fluid biochemical analysis underwent on 38 patients performed well at differentiation mucinous from non-mucinous cysts when combined CEA (>72.35 ng/ml) and amylase (<461.7 IU/L) can get a high accuracy (85.7%) and specificity (93.8%), a low sensitivity (78.9%). EUS-FNA cyst fluid cytology analysis had a high accuracy of 98.1% (53/54) in dividing cystic lesions into benign and malignant while its accuracy of diagnosis in cystic classification was 87.0% (20/23). There are 14 patients undergoing biopsy of cystic wall through SpyGlass among 59 surgical patients and 3 cases got final definitive diagnosis through pathology of the cystic wall’s biopsy which was in accordance with surgical pathology which 11 cases failed in sample obtaining and sectioning. Mild pancreatitis occurred in 2 cases and moderate fever occurred in 1 case among 36 cases undergoing ablation and none of the patients reported any severe complications. Of the 23 cases who were followed up for 3.9 months (rang 1.5-12 months), 4 cases had complete resolution and 13 cases had partial resolution. The resolution rate was 73.9%.

Conclusion: EUS possesses high accuracy in differentiating benign lesions from malignancy in pancreatic cystic lesions. EUSFNA fluid biochemical and cytology analysis have distinct advantages in distinguishing different kinds of pancreatic cystic lesions while biopsy of cystic wall through SpyGlass has high accuracy. EUS-guided pancreatic cystic lesions ablation with lauromacrogol is safe and efficient, and it may replace surgical operation and become the major treatment. Further studies involving larger populations and multiple-center are warranted.

Biography:

Mukherjee received her Ph.D. at the age of 26 in Immunology from London, UK. After postdoctoral training at Pennsylvania State University, Mukherjee held faculty appointments at IU Medical Center, Mayo Clinic, and is currently Chair and Belk Endowed Professor of Cancer Research at University of North Carolina at Charlotte. Mukherjee has published ~100 articles including patents. Her lab has received major federal/foundation grants totaling >$13MM. Mukherjee co-founded OncoTab Inc., a biotechnology company.  She is the 2015 recipient of the O. Max Gardner award, the highest faculty accolade given by the Board of Governors of the University of North Carolina.

Abstract:

The study explores a novel strategy to deliver drugs to pancreatic ductal adenocarcinoma (PDA) to combat a) chemo-resistance and b) toxicity associated with systemic delivery of chemotherapeutic drugs. We also report the development of an accurate diagnostic/imaging test for PDA. Globally, this year, it is estimated that ~350,000 patients will die of PDA. Development of a biomarker for accurate diagnosis and targeted therapy to improve patient outcome are of paramount importance. Emerging evidence suggests that the capability of a tumor to propagate is dependent on a small subset of cells within the tumor, termed cancer stem cells (CSCs). Traditional treatments can miss the CSCs due to its quiescent property. We have developed a novel monoclonal antibody (designated TAB004) that recognizes a previously hidden cancer biomarker tMUC1 (tumor-specific MUC1). We have reported that tMUC1 is expressed on 95% of PDA and on all PDA-associated CSCs. In this study, we have covalently bound TAB004 to various drug-loaded PLGA (Poly lactic-co-glycolic acid) and silica-based nanoparticles (NPs). These formulations specifically target the tMUC1 on PDA, and associated CSCs sparing normal tissue. We hypothesize that NPs bound to TAB004 will enable the use of highly cytotoxic anti-cancer treatments at localized concentrations making the treatment more effective at lower doses, increasing its therapeutic index and limit toxicity. We will present the results on the localization and therapeutic efficacy of such formulations in appropriate mouse models. Further, we will report on the diagnostic/imaging application of TAB004 to monitor response to therapy.

Biography:

Rajgopal Govindarajan has completed his PhD from University of Nebraska Medical Center and Post-doctoral studies from University of Washington School of Pharmacy. He is currently an Associate Professor at the College of Pharmacy, Ohio State University.

Abstract:

Identification of epigenetic reversal agents for use in combination chemotherapies to treat human pancreatic ductal adenocarcinomas (PDAC) remains an unmet clinical need. Pharmacological inhibitors of enhancer of zeste homolog 2 (EZH2) are emerging as potential histone methylation reversal agents for the treatment of various solid tumors and leukemia; however, surprisingly small set of mRNA targets identified with EZH2 knockdown suggests novel mechanisms that contribute to their anti-tumorigenic effects. Here we report 3-deazaneplanocin-A (DZNep), an inhibitor of S-adenosyl-L-homocysteine hydrolase and EZH2 histone lysine-N-methyltransferase, to significantly reprogram noncoding miRNA expression and dampen TGF-β1-induced epithelial-to-mesenchymal (EMT) signals in pancreatic cancer. In particular, we identify miR- 663a and miR-4787-5p as PDAC-downregulated miRNAs that are reactivated by DZNep to directly target TGF-β1 for RNA interference. Lentiviral overexpression of miR-663a and miR-4787-5p reduced TGF-β1 synthesis and secretion in PDAC cells and partially phenocopied DZNep’s EMT-resisting effects, whereas locked nucleic acid (LNA) antagomiRs counteracted them. In vivo, DZNep, miR-663a, and miR-4787-5p reduced tumor burden and metastases in an orthotopic mouse pancreatic tumor model. Taken together, these findings suggest the epigenetic reprogramming of miRNAs by synthetic histone methylation reversal agents as a viable approach to attenuate TGF-β1-induced EMT features in human PDAC and uncover putative miRNA targets involved in the process.

Biography:

Chrystal Louis obtained her MD from Tulane University School of Medicine and her MPH from Tulane University School of Public Health and Tropical Medicine. She completed her pediatric oncology training at the Texas Children’s Cancer and Hematology Centers and Baylor University School of Medicine. As a member of the Center for Cell and Gene Therapy, she became a successful translational researcher in the field of virus-specific and chimeric antigen receptor-specific cellular immunotherapy. Dr Louis joined the Discovery Division of Merrimack Pharmaceuticals in 2014 and is currently the Medical Director and Project Leader of the Istiratumab (MM-141) team.

Abstract:

Pancreatic cancer often presents as inoperable, locally-advanced or metastatic disease. With traditional forms of chemotherapy, long-term survival for patients with metastatic disease is less than 5%. Due to the heterogeneity within pancreatic lesions, investigators are beginning to tailor treatment regimens to the pathology and biology of individual tumors. Using a systems engineering approach, we have developed both targeted and untargeted nanoliposomal molecules as well as signaling inhibitors to combat malignant solid tumors like pancreatic cancer. Nal-IRI (liposomal irinotecan, ONIVYDE®), MM-310 (EphA2-targeted docetaxel nanoliposome), and istiratumab (a tetravalent IGF-1R and ErbB3 inhibitor) are three examples of novel therapeutic candidates designed to utilize the tumor biology and microenvironment to improve anti-tumor efficacy. Nal-IRI takes advantage of both leaky vasculature and tumor associated macrophages within the tumor environment to enhance delivery and activity of SN-38. With an EphA2-targeting arm, MM-310 is a next generation nanoliposome providing enhanced delivery and specificity of docetaxel to EphA2-positive malignancies. Lastly, istiratumab inhibits pro-survival signaling through the PI3K/AKT/mTOR pathway by blocking and subsequently stripping IGF-1R and ErbB3 from the surface of tumor cells. Nal-IRI is currently being investigated in combination with 5FU, leucovorin, and oxaliplatin in patients with newly diagnosed metastatic pancreatic cancer. Targeted (biomarker-driven) patient selection is being utilized in both the Phase 1 study of MM-310 for patients with EphA2-positive cancers, and in the Phase 2 study of istiratumab in combination with nab-paclitaxel and gemcitabine in newly diagnosed metastatic pancreatic cancer patients who have elevated levels of free IGF-1 in their serum.