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

Biography:

Jose Mario F De Oliveira is an Associate Professor of Medicine in the Department of Medicine of Universidad Federal Fluminense, in the State of Rio de Janeiro, Brazil. He is also one of the Deputy Editors for Diabetes of The British Medical Journal. He has published a number of papers and served as a reviewer or author and co-author for many prestigious medical journals like “Hypertension”, “The American Journal of Hypertension”, “The Journal of the American Society of Nephrology”, “The British Medical Journal”, and the “New England Journal of Medicine”. His main interests are in the clinical research of diabetes and hypertension. He is a Certified Preventive Cardiologist, Nephrologist and Adult Intensive Care Unit Physician. Finally, he was a Post-Doctoral Clinical and Research Fellow at the Endocrinology-Hypertension-Diabetes Division of the Brigham & Women’s Hospital at Harvard Medical School, in Boston, USA and is one of the two authors of the recent electronic Diabetes e-book published and edited by The British Medical Journal for all doctors world-wide.

Abstract:

Albeit ACE-Is or ARBs have an undoubtful clinical benefit in diabetic and non-diabetic heart failure, their role as first line drug therapies in type 2 diabetics with hypertension or chronic kidney diseases have been recently put into question despite their – mild - anti-proteinuric effects, both as anti-hypertensive or as renoprotective agents specially in type 2 diabetes mellitus subjects. Angiotensin II, the main octapeptide “defence” molecule and “effector” of the renin-angiotensin-aldosterone system (RAS) has a variety of homeostatic actions in states of health and disease like regulating the salt and potassium balance for blood preesure homeostasis, keeping up the glomerular filtration rate under normal values and modulating the sympathetic nervous system, All in conditions of hypovolemia or salt depletion in order to keep our systemic – blood pressure - renal hemodynamics, and salt balance in good shape. In our Talk, we intend to show the most recent randomised clinical trial and observational evidences about how to deal with these drugs in the various clinical scenarios of diabetics, with and without chronic kidney diseases in order to keep our homeostasis in the right direction.

Biography:

Dawn E Quelle has obtained her PhD in Biochemistry and Molecular Biology from the Pennsylvania State University. In her Post-doctoral work with Dr. Charles Sherr at St Jude Children’s Research Hospital, she studied cell cycle control and discovered the ARF tumor suppressor. She is an Associate Professor of Pharmacology at the University of Iowa and Leader of the Cancer Genes and Pathways Program in the Holden Comprehensive Cancer Center. Her research explores mechanisms of tumor suppression with a focus on the molecular and in vivo functions of ARFRABL6As binding partners, such as RABL6A, in cancer.

Abstract:

A better molecular understanding of pancreatic (neuroendocrine tumors PNETs) is needed to improve patient diagnosis and treatment. The PI3K/Akt/mTOR pathway is aberrantly activated in PNETs resulting in everolimus (mTOR inhibitor)-based therapies. However, sustained mTOR inhibition has the unintended consequence of hyper-activating Akt, thereby promoting drug resistance. Our data suggests that RABL6A, a novel oncoprotein amplified in PNETs, is a key regulator of this clinically relevant pathway. We found that RABL6A is essential for PNET cell proliferation and survival, and its loss dramatically reduces both Akt1 and Myc expression and activity. Given the central role of Akt1 and Myc in promoting tumorigenesis, we hypothesized that reinstating their activity would rescue the arrest phenotype caused by RABL6A loss. Individual restoration of Akt1 or c-Myc in –depleted PNET cells partially rescued the G1 phase arrest and induced S phase entry. This coincided with decreased expression of the cell cycle inhibitor, p27Kip1, and increased levels of CKS1B, a Myc transcriptional target that promotes p27 degradation. Notably, neither Akt nor Myc activation was sufficient to restore proliferation in the absence of RABL6A since cells became arrested in S-G2/M or died via apoptosis. Thus, controls multiple pathways essential for PNET cell cycle progression and survival. We are currently testing if RABL6A status in PNETs predicts responsiveness to clinical inhibitors of Akt, mTOR and Myc. These studies identify RABL6A as a new essential regulator of Akt1-mTOR and Myc signaling pathways, providing compelling mechanistic insight into the oncogenic function of RABL6A in PNETs.

Biography:

Flavio Amaro Oliveira Bitar Silva has graduated from UFMG School of Medicine (Belo Horizonte - MG, Brazil) in 2006. He has finished his specialization in Surgery in 2010 (General Surgery + Trauma and Urgency Surgery). He has completed his specialization in Gastrointestinal Endoscopy in 2013, on Santa Casa de Sao Paulo (Sao Paulo - SP, Brazil), where he spent 2 more years learning Endoscopic Retrograde Colangiopancreatography (ERCP) and Endoscopic Ultrasound. He has few papers published in some of reputed journals in Endoscopy field and he is beginning his professional career.

Abstract:

A young girl presented with abdominal pain and jaundice of 1 month’s duration. She had conjugated hyperbilirubinemia and negative hepatitis serology. Computed tomography showed a mass in the head of the pancreas, with foci of calcification and cystic/necrotic areas. Pancreatoblastoma and Frantz Tumor were suspected. The patient underwent a cholecystojejunal anastomosis and intraoperative biopsy of the pancreatic mass yielded inconclusive results. She was referred for endoscopic ultrasound (EUS) to reevaluate the pancreatic mass. EUS showed a solid–cystic lesion in the head of the pancreas. EUS-guided fine-needle aspiration of the pancreatic mass was performed. Cytopathologic evaluation and immunohistochemical analysis confirmed the diagnosis of peripheral primitive neuroectodermal tumor (PNET). PNET belongs to a rare group of tumors called the Ewing sarcoma family of tumors. Pancreatic PNETs are extremely rare and highly aggressive. Metastasis and recurrence are common. With modern multidisciplinary treatment, long-term survival can be achieved in 70% to 80% of patients with disease that has not metastasized. The correlation of clinical symptoms with imaging, cytopathologic, and immunohistochemical analysis is important to establish the diagnosis. An atypical rosette array of the cells, cytoplasmic neuronal secretory granules and neurofilaments, and pyknotic nuclear granules areimportant diagnostic criteria. Most tumors of the Ewing sarcoma family express high levels of a cell surface glycoprotein, CD99 [13,14]. According to a 2014 review article, 14 cases of pancreatic PNET have been reported. This is the first case of a pancreatic PNET diagnosed by EUS.

Biography:

Chong Yang has completed his PhD at the age of 28 years from Wuhan Union Hospital, Huazhong University of Science and Technology, and currently working as a surgeon in Hospital of the University of Electronic Science and Technology of China and Sichuan Provincial People's Hospital. His main research subject is severe acute pancreatitis, and published more than 10 manuscripts in reputed journals and has been serving as an editorial board member of repute.

Abstract:

Objectives: This study aimed to compare the effects of hydroxyethyl starch (HES) 130/0.4 combined with crystalloid solution with those of crystalloid solution alone on inflammatory variables (IL-1, IL-6 and IL-8 and TNF-­α), immunologic variables (CD4/8+ T cells), fluid balance (FB) negative (-) rate and renal function for severe acute pancreatitis (SAP) patients.

Methods: In this retrospective study, 59 patients received 6% HES 130/0.4 combined with crystalloid solution for fluid resuscitation (HES group), and 61 patients received only crystalloid solution simultaneously (control group) after admission. The serum values of IL-1, IL-6, IL-8 and TNF-α were measured on days 1, 2, 4 and 8. The peripheral blood CD4/8+ T lymphocyte rates, serum BUN and Cr values were measured on days 1, 4 and 8. The patients with FB(-) rates were recorded from days 1 to 8.

Results: Interaction term analysis (hospital stay and fluid resuscitation methods) based on mixed-effects regression model revealed significantly lower levels of IL-1 [risk ratio (RR): -0.406, P*: 0.041] and TNF-α (RR: -1.189, P*: 0.013) in the HES group compared with control group. The curve's RR difference was not significant for IL-6,CD4/8+ T lymphocyte rate, BUN and Cr values (P*>0.05). There was a significantly higher rate of patients with FB(-) from days 4 to 8 in the HES group (P<0.05).

Conclusion: HES 130/0.4 combined with crystalloid fluid resuscitation could decrease the IL-1 and IL-8 concentration, shorten the duration of positive fluid balance, and preserve patient’s immune status and renal function during the early stage of SAP.

Biography:

Ming Xiang has completed her PhD from Tongji Medical College, Huazhong University of Science and Technology. She is the Vice Director of School of Pharmacy, Tongji Medical College. She is a qualified Professor with track record not only within the pathogenesis of autoimmune diseases and chronic inflammation, the mechanism of regulation and induction of antigen-specific immune tolerance by Treg and DC for the therapy of autoimmune disease, but also the mechanism of pancreatic oncogenesis. She has published more than 25 papers in reputed journals and has been serving as an Editorial Board Member of repute, obtained 2 patents, an Academic Award and hosted several NSFC projects.

Abstract:

Regenerating islet-derived protein 3, regulates a variety of important pathologic physiology processes including inflammation, cancer control and cell proliferation. RegIII and IL-6 share the same pathway to accentuate inflammation, and suppressor of cytokine signaling 3 (SOCS3) is a negative regulator of this pathway to bear tumor suppressor function. We studied the immunological mechanisms of Reg3g for promoting the pancreatic cancer. We successfully established subcutaneous transplantation tumor model and pancreatic carcinoma in situ model in C57/BL6j mice. Firstly, we determined critical target cells of Reg3g such as dendritic cells (DC), and CD8+ T cells and CD4+ CD25+ Foxp3+ T cells (Treg); Secondly, we found that Reg3g upregulated key genes in pancreatic tissue such as STAT3, Ki67, Caspase3 gene and downregulated SOCS3 gene, which being collaborative with Th2 type cytokines inhibited tumor immune response, and promoted malignant tumor cell proliferation; Lastly, we confirmed Reg3g inhibited DC migration and phagocytosis, attenuated CD8+ T cells infiltration, decreased negative regulatory factors such as CD152 and PD-1, PD–L1, interfered interaction between CD8+ T cells and DC, inhibited CD8+ T to cells cytotoxicity tumor, and promoted pancreatic cancer formation.

Biography:

Sajida Qureshi is a Professor of Surgery from Dow University of Health Sciences. She has graduated from Dow Medical College Karachi Pakistan in 1996, Fellow of College of Physicians and Surgeons Pakistan, 2002 and Fellow of Royal College of Surgeons, Ireland 2003. She has indexed 22 publications in various journals. She was the Supervisor of Post-graduate training in Surgery in Pakistan. She is a reviewer of two journals in Pakistan. She has her special interest in Cancer Surgery.

Abstract:

Introduction: Pancreaticoduodenectomy (Whipple procedure) is a treatment of choice for patients with resectable carcinoma head of pancreas, lower cholangiocarcinoma, duodenal and ampullary and periampullary carcinomas. One of the much-dreaded complications of pancreaticoduodenectomy is pancreatic anastomotic leak leading to the pancreatic fistula formation, which can lead to septicemia and resultant complications leading to death of the patient. Stenting the pancreaticoenteric anastomosis has been postulated as reducing the pancreatic anastomotic leak and fistula rates up until now there is no convincing evidence supporting this fact.

Objective: To compare clinically relevant pancreatic fistula rates in patients with stinted versus non-stinted pancreaticojejunostomy.

Material & Methods: The study was conducted at Surgical Unit of 4 civil hospitals in Karachi, Pakistan, over a period of six years from September 2009 to August 2015. A total of 102 patients presenting to the unit with diagnosis of periampullary carcinoma, carcinoma head of pancreas, duodenal carcinoma involving the second part, and lower cholangiocarcinomas resectable on CT scan were included in the study. The primary study end point was pancreatic fistula or leakage, defined as amylase rich fluid (amylase concentration >3 times the upper limit of normal serum amylase level) collected from the peripancreatic drains on day 1, 3 and 7 post operatively which persisted beyond five days.

Results: A total of 102 patients were included in the study. Male to female ratio was (72:30). Mean age of the study population was 52.68 years, SD 11.6 (range 30-80 years) 53 patients had Pd stent (51.9%) while 49 did not have stented pancreaticojejunostomy (48%). Anastomotic leak was seen in 36 patients (35%). 37.7% patients with pancreatic stent and 32.6% patients without stent had a leak (p value 0.371).

Conclusion: There was no statistically significant difference in the pancreatic fistula rates between stinted and non-stinted anastomosis. We conclude that stinted pancreaticojejunostomies do not lead to decreased pancreatic fistula rates.

Biography:

Jose Mario F De Oliveira is an Associate Professor of Medicine in the Department of Medicine of Universidad Federal Fluminense, in the State of Rio de Janeiro, Brazil. He is also one of the Deputy Editors for Diabetes of The British Medical Journal. He has published a number of papers and served as a reviewer or author and co-author for many prestigious medical journals like “Hypertension”, “The American Journal of Hypertension”, “The Journal of the American Society of Nephrology”, “The British Medical Journal”, and the “New England Journal of Medicine”. His main interests are in the clinical research of diabetes and hypertension. He is a Certified Preventive Cardiologist, Nephrologist and Adult Intensive Care Unit Physician. Finally, he was a Post-Doctoral Clinical and Research Fellow at the Endocrinology-Hypertension-Diabetes Division of the Brigham & Women’s Hospital at Harvard Medical School, in Boston, USA and is one of the two authors of the recent electronic Diabetes e-book published and edited by The British Medical Journal for all doctors world-wide.

Abstract:

Since the published results of the UKPDS, the reduction of HbA1c levels has been the universal and even more than that, ubiquitous paradigm in clinical guidelines, in older times for macrovascular diabetic complications and in more recent times for microvascular diabetic complications. This overconfidence in the reliability of “safe” HbA1c levels, unfortunately, has increased over the last decades the frequency of severe hypoglycemic episodes, a high speed delivery onto the market of unsafe new anti-diabetic drugs, forgetting about the endponts that mostly matter to the diabetic patient survival and quality of life based on each days shorter and biased clinical trials. The purposes of this talk will be to explain for the audience; the concepts of a soft, a hard and a surrogate outcome in the clinical spectrum of diabetes and their clinical relevance to treatment and prognosis.

Biography:

Zhaohui Xua has received his PhD in Pharmacognosy in 2000 and Fructus Arctii is the object of his Doctoral research topic. He has committed his research to the treatment of Fructus Arctii in type 2 diabetes for over 20 years. He has published nearly 20 papers on the anti-diabetic activity of Fructus Arctii. He has made a useful exploration of the material basis and mechanism of the anti-diabetic activity of Fructus Arctii.

Abstract:

Research Background: Fructus Arctii, called “Niubangzi” in China (Great burdock achene in English), is a well-known Chinese materia medica. It is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and was included in the Chinese pharmacopoeia for its traditional therapeutic actions.

Aim of the study: To study antidiabetic activity and mechanism of total lignans from Fructus Arctii (TLFA) in KKAy mice, a spontaneous type 2 diabetic animal model.

Materials & Methods: TLFA was extracted from Fructus Arctii and purified as described previously. Male KKAy mice and C57BL/6J mice were used in this study, KKAy mice were gavaged once daily with either solvents (0.3% CMC-Na), TLFA (250 mg/kg), TLFA (125 mg/kg) or Metformin (200 mg/kg) for 11 weeks. Besides common evaluation indexes of antidiabetic activity such as blood glucose level, body weight, oral glucose tolerance test (OGTT), glycated hemoglobin, as well as lipid metabolism parameters in mice serum was analyzed. Histopathological examination of the pancreas, white adipose tissue, liver and skeletal muscle was performed by optical microscope. The gene expressions of protein tyrosine phosphatase 1B (PTP1B), leptin, adiponectin and glucose transporter type 4 (GLUT4) were determined by real-time PCR. The protein levels of the above molecules and PPAR-γ, ACC, p-ACC, AKT, phospho-Akt (p-Akt), AMPK, p-AMPK, insR and GSK3β were measured by Western blot.

Results: TLFA demonstrated significant hypoglycemic activity in KKAy mice and showed potential to inhibit weight gain. The

results of real-time PCR and Western blot showed that TLFA downregulated leptin, PTP1B while it upregulated adiponectin and GLUT4 (p<0.05). The protein level of AMPK, p-AMPK, GLUT4 and insR was also increased while the protein level of ACC, p-Akt, Akt was decreased (p< 0.05).

Conclusion: The results of this study indicate that TLFA has significant antidiabetic potential in KKAy mice. And this potential could be associated with activation of AMPK, insR and GLUT4 pathways and upregulated gene expression of adiponectin and GLUT4, with downregulation of Akt pathway and downregulated gene expression of leptin and PTP1B. It has a great potential to be further developed as a novel therapeutic agent for diabetes in humans.

Biography:

Flávio Amaro has graduated from UFMG School of Medicine (Belo Horizonte - MG, Brazil) in 2006. He has finished his specialization on surgery in 2010 (General Surgery + Trauma and Urgency Surgery). He has completed his specialization in Gastrointestinal Endoscopy in 2013, on Santa Casa de São Paulo (São Paulo - SP, Brazil), where he spent 2 more years learning Endoscopic Retrograde Colangiopancreatography (ERCP) and Endoscopic Ultrasound. He has few papers published in some of reputed journals in endoscopy field and he is beginning his professional career

Abstract:

A young girl presented with abdominal pain and jaundice of 1 month’s duration. She had conjugated hyperbilirubinemia and negative hepatitis serology. Computed tomography showed a mass in the head of the pancreas, with foci of calcification and cystic/necrotic areas. Pancreatoblastoma and Frantz Tumor were suspected. The patient underwent a cholecystojejunal anastomosis, and intraoperative biopsy of the pancreatic mass yielded inconclusive results. She was referred for endoscopic ultrasound (EUS) to re-evaluate the pancreatic mass. EUS showed a solid–cystic lesion in the head of the pancreas. EUS-guided fine-needle aspiration of the pancreatic mass was performed. Cytopathologic evaluation and immunohistochemical analysis confirmed the diagnosis of peripheral primitive neuroectodermal tumor (PNET).

PNET belongs to a rare group of tumors called the Ewing sarcoma family of tumors. Pancreatic PNETs are extremely rare and highly aggressive. Metastasis and recurrence are common. With modern multidisciplinary treatment, long-term survival can be achieved in 70% to 80 % of patients with disease that has not metastasized.

The correlation of clinical symptoms with imaging, cytopathologic, and immunohistochemical analysis is important to establish the diagnosis. An atypical rosette array of the cells, cytoplasmic neuronal secretory granules and neurofilaments, and pyknotic nuclear granules are important diagnostic criteria. Most tumors of the Ewing sarcoma family express high levels of a cell surface glycoprotein, CD99 [13, 14].

According to a 2014 review article, 14 cases of pancreatic PNET have been reported. This is the first case of a pancreatic PNET diagnosed by EUS. 

Biography:

Yoram Oron has completed his PhD from Hebrew University, Jerusalem and postdoctoral studies from University of Virginia School of Medicine. He taught physiology and pharmacology at Tel Aviv University (TAU) and served, among other functions, as Department Chair, and TAU Director of International Academic Relations. His career included Visiting Associate Professorship at Cornell Medical School and numerous periods as Visiting Scientist at NIDDK, NIH. He has published more than 110 papers in reputed journals and has served as an editorial board member of several journals. Although still actively in research, he is currently a TAU Professor Emeritus

Abstract:

It is generally accepted that overexpression of Plaminogen Activator Inhibitor 1 (PAI-1) correlates with worse prognosis and more invasive phenotype of many cancers, including Pancreatic Adenocarcinoma (PAC).  We down-regulated PAI-1 expression in PANC-1 cells via shRNA knockdown (KD).  The down-regulated variant (PD-PANC) exhibited neural morphological traits vs. cuboidal morphology of WT PANC-1s or vector-transfected cells. RT-PCR demonstrated that KD of PAI-1 leads to decreased expression of mesenchymal markers transcripts concurrently with increased expression of epithelial and neural transcripts, suggesting partial mesenchymal-to-epithelial transition. Importantly, PD-PANC1s expressed markedly more E-cadherin in a larger proportion of cells, whereas TUBB3 was expressed predominantly in cells with neural morphology. Yet, despite this apparent more epithelial phenotype, PD-PANC-1s exhibited more invasive behavior in vitro. Although the invading cells expressed more PAI-1 and less E-cadherin transcripts than non-invaders, it could not explain the observed increase in invasiveness . Using fluorescent supravital staining in a mixed vector/PD-PANC-1 population, we demonstrated that cells that down-regulated PAI-1 created environment promoting invasion of the few cells expressing high PAI-1 level. We previously reported that PD-PANCs exhibit higher uPA activity and continuously convert plasminogen to plasmin, which have been shown to activate matrix matalloproteinases. Indeed, inclusion of plasminogen enhanced invasion of PD-PANC-1s. In conclusion, our results suggest that fine balancing of different activities rather than extensive ablation of the “offending” PAI-1 protein  maybe a better strategy in maintaining a less aggressive PAC phenotype.

Biography:

Manash Ranjan Sahoo completed his Masters degree in surgery in the year 1994 from Utkal University and followed it up with Fellowship in Surgical Gastroenterology in 1999 from Sri Ramachandra Medical College & Research Institute(Deemed University),Dr.Sahoo was invited to present his work in SAGES conference in Baltimore,USA in 2013 & was a plenary presenter in IHPBA World Congress in 2014 in Seoul,South Korea.He is an Associate Professor in S.C.B Medical College in Odisha,India & he he has 41 Pubmed indexed publications to his credit & he is the chief coordinator of Advanced Laparoscopic Surgery Training Programme in his Institution

Abstract:

AIM: Aim of  this  study  is  to  evaluate  the feasibility  of  Laparoscopic Roux-en-Y Cystojejunostomy using Suture  for pseudocyst  of  tail  of  pancreas. 

MATERIALS AND METHODS: This  is  a  retrospective  study  of  13  patients   of   pseudocyst  of  tail  of  pancreas  from   April  2007  to  November  2013. Age  of  the  patients  including  both  male  and  female  ranged  from   15  to  64  years. All  patients  were  subjected  to  Laparoscopic Roux-en-Y Cystojejunostomy using nonabsorbable suture.These  patients  were  followed  for  a  period  of  18  months  assessing  first  bowel movement, duration  of  surgery, hospital  stay, anastomosis  leak, recurrence  and  morbidity.

RESULT: Duration  of  surgery  was  156.6 ± 10.4  minutes. Postoperatively, the  mean  time  for  the  first  bowel  movement  was  36 hrs . Mean  hospital  stay  was  six (range: 5-7)  days. There  were  no  anastomosis leaks  in  any  patient. There  were  no  recurrences. Morbidity  was  comparable  to  any  other  laparoscopic  surgery.

CONCLUSION: We conclude that Laparoscopic Roux-en-Y Cystojejunostomy using Suture  for  pseudocyst  of  tail  of  pancreas  is  a  safe, effective,compliant  and  feasible  procedure.

Biography:

Daria Dranka-Bojarowska  graduated Silesian University School of Medicine in 2000. She is assistant in The Department of Gastrointestinal Surgery, Medical University of Silesia –a leader center of pancreatic surgery in Poland. She has completed her PhD in 2014 from Silesian University School of Medicine, She is author more than 20 medical articules and conferences abstracts. She has published 7 papers in reputed journals.

Abstract:

The aim of this study was a comparative analysis of the concentrations in serum of adipocytokines: adiponectin and leptin and CA 19-9 in patients with pancreatic cancer (PC), chronic pancreatitis (CP) and control group (CG). The study was performed in a group of 90 patients. The serum samples were taken from patients and the concentration of adiponectin, leptin, CA 19-9 and CEA were evaluated. The revealed concentrations levels of the adiponectin were significantly higher in the PC serum samples compared to the CP and CG. There was no significant correlation between increased adiponectin concentration and body fat mass in the PC group. The concentration of leptin was significantly lower in CP serum samples compared to PC and CG. The concentration of leptin was similar in the PC and CG. The concentration of leptin was mainly dependent on body fat mass and fat distribution. Additionally, measurement of waist circumference and body composition was recorded using bioelectrical impedance analysis. Significantly higher concentration levels of adiponectin in the PC group, independent of body fat mass, may play a potential role as a new tumor marker in PC and might be useful in the differential diagnosis between PC and CP. Author perform further investigation to validate this statement. To our knowledge, this was the first study evaluating not only BMI but also the content and distribution of body fat in patients with PC and CP.

Biography:

Dawn Quelle obtained her Ph.D. in Biochemistry and Molecular Biology from the Pennsylvania State University. In her post-doctoral work with Dr. Charles Sherr at St. Jude Children’s Research Hospital, she studied cell cycle control and discovered the ARF tumor suppressor. She is an Associate Professor of Pharmacology at the University of Iowa and Leader of the Cancer Genes and Pathways Program in the Holden Comprehensive Cancer Center. Her research explores mechanisms of tumor suppression with a focus on the molecular and in vivo functions of ARF’s binding partners, such as RABL6A, in cancer.

Abstract:

            A better molecular understanding of pancreatic neuroendocrine tumors (PNETs) is needed to improve patient diagnosis and treatment. The PI3K/Akt/mTOR pathway is aberrantly activated in PNETs resulting in everolimus (mTOR inhibitor)-based therapies. However, sustained mTOR inhibition has the unintended consequence of hyper-activating Akt, thereby promoting drug resistance. Our data suggests that RABL6A, a novel oncoprotein amplified in PNETs, is a key regulator of this clinically relevant pathway. We found that RABL6A is essential for PNET cell proliferation and survival, and its loss dramatically reduces both Akt1 and Myc expression and activity. Given the central role of Akt1 and Myc in promoting tumorigenesis, we hypothesized that reinstating their activity would rescue the arrest phenotype caused by RABL6A loss. Individual restoration of Akt1 or c-Myc in RABL6A-depleted PNET cells partially rescued the G1 phase arrest and induced S phase entry. This coincided with decreased expression of the cell cycle inhibitor, p27Kip1, and increased levels of CKS1B, a Myc transcriptional target that promotes p27 degradation. Notably, neither Akt nor Myc activation was sufficient to restore proliferation in the absence of RABL6A since cells became arrested in S-G2/M or died via apoptosis. Thus, RABL6A controls multiple pathways essential for PNET cell cycle progression and survival. We are currently testing if RABL6A status in PNETs predicts responsiveness to clinical inhibitors of Akt, mTOR and Myc. These studies identify RABL6A as a new essential regulator of Akt1-mTOR and Myc signaling pathways, providing compelling mechanistic insight into the oncogenic function of RABL6A in PNETs

Biography:

Ben Darbro obtained his M.D. and Ph.D. in 2007 from the University of Iowa.  His thesis research examined mechanisms of human epithelial cell immortalization and p16INK4a induced telomere-independent senescence. Following a residency in Clinical Pathology and fellowship training in Molecular Genetic Pathology, he joined the Pediatrics Department at the University of Iowa and assumed Directorship of the Shivanand R. Patil Cytogenetics and Molecular Laboratory. His research utilizes sophisticated genomic methodologies to discover genetic determinants of intellectual disability/cognitive developmental delay as well as recurrent genomic aberrations in neuroendocrine tumors that can aid in diagnosis, prognosis, and therapeutic decision making

Abstract:

Neuroendocrine tumors can develop in multiple anatomic locations including the gastrointestinal tract, pancreas, lungs, cervix, thymus, and thyroid.  Approximately 50% of these tumors are metastatic at the time of diagnosis complicating identification of the primary tumor’s site of origin.  Determining the tumor site of origin is particularly important in NETs as both prognosis and treatment differ depending on where the tumor originated.  Thus, the ability to determine NET site of origin can be of critical importance in the clinical management of these patients.  To this end, we performed array-based comparative genomic hybridization to identify site of origin specific copy number variants in NETs of pancreatic (n=13) and ileal (n=10) origin.  We used gene expression profiling to prioritize those genomic gains or losses that were associated with concordant differential gene expression.  Four copy number variable regions exhibited statistically significant differential copy number status reflective of NET site of origin (p < 0.001): 18q, 19q, 12p, and 9q.  Several of these loci also exhibited differential gene expression changes suggesting they are functional copy number changes as opposed  to by-stander genetic lesions.  We tested the ability of fluorescence in situ hybridization (FISH) to identify these chromosomal lesions in formalin fixed paraffin embedded (FFPE) NET tissue.  This work lays the foundation for the development of a clinical diagnostic assay that can be performed on all newly diagnosed NETs of unclear site of origin

Biography:

Yi Wang has completed her PhD at the age of 31 years from Sichuan University and postdoctoral studies from the Ohio State University. She is the associate professor from Department of Pharmacy, Sichuan Academy of Medical Science & Sichuan Provincial People’s Hospital. She has published more than 30 papers in reputed journals and 14 papers are first author or the coppresonding author. She has one patent, and has been serving as an editorial board member of repute.      

Abstract:

Diabetes is a kind of metabolic disease, which causes considerable morbidity in the world. Although pancreas transplantation and islet transplantation has prominent future, we still confront the main difficulty of organ shortage. Thus, a primary and fundamental effective therapy for diabetes is to develop ways to increase beta cell numbers.Here, we reported that under the stimuli of homones, pancreatic duct epithelial cells, also known as pancreatic progenitor cells, could be differented into insulin-secreting islet β-cells.

In this study, we collected pregnant rat serum and added to the culturing medium of isolated rat pancreatic duct epithelial cells.  After 7 days of culturing, the pancreatic progenitor cells will be aggregrated (Figure 1). Then we compared the gender difference of the pancreatic progenitor cells, and also the dosage of pregnant serum on the efficiency of differentiation. As observed in Figure 2, all cells treated with pregnant serum experienced expansion (A-D), aggregation (E-H), and islet-like cells formation (I-L) stages. Higher concentration of pregnant serum treated cells (L,J) generate more islet-like cells compared to those of lower ones (I, K). Pancreatic duct epithelial cells isolated from female rats formed larger islet-like sphere compared to those of male ones. However, pancreatic duct epithelial cells cultured with FBS could not form islet-like cells  (N, low concentration of  FBS control; O, high concentration of FBS control). Then the differented islet-like cells were determined by dithizone staining (P) and aggregated pancreatic duct cells were determined by insulin staining (M). Judged from these two pictures, no matter the aggregrated cells or the sphere-shaped ones are capable of secreting insulin.

In conclusion, the pancreatic progenitor cells could be differented to insulin-secreting islet β-cells by the pregnant serum, which indicats the therapeutic potential of hormone therapy in preventing and/or treating diabetes.

Biography:

Khaled Abou-El-Ella is Professor of Hepatopancreatobilliary surgery (HPB), Gastro-Intestinal Surgery and Liver Transplantation. He is the Head of the Surgical Department at the National Liver Institute, Menoufiya University, Egypt. He is the Director of the Liver Transplantation Program in New Alex Medical Center, Alexandria, Egypt. He is the Consultant of gastrointestinal and liver specialized hospital, Alexandria, Egypt. He graduated from Faculty of Medicine, Alexandria University in 1984. He obtained his PhD from Ain Shams University, Egypt in 1997 and Surgical and Research Fellowship in the University of Tennessee, Memphis Tennessee, 1994-1996.

Abstract:

Introduction & Aims: Resection of pancreas, in particular Pancreaticoduodenectomy (PD), is a complex procedure, with the morbidity rate remains high in the range of 30% to 65%. Most of these complications are related to pancreatic fistula (PF). The aim is to evaluate the feasibility of newly suggested technique for pancreaticojejunostomy (PJ) to prevent PF.

Methods: From January 2014 till June 2015, 15 cases underwent pyloric preserving PD for periampulary carcinoma with pancreaticoenteric anastomosis done by using PJ using a modified technique including: End-to-end suturing of intestinal jejunal loop to pancreatic serosa in single interrupted layer, which then covered by reinforcing anterior second layer using “lesser omental pedicled patch” fixed over the first layer by interrupted sutures (pancreatic duct was stented in all cases).This group of patient was considered as (group 1) and it was compared to another group of 15 cases, previously operated using the traditional PJ technique, named (group 2) as regard applicability and efficacy of the modified technique in controlling PF.

Results: The new technique was easily applicable for all cases, tension free and safe. With using the new technique no cases (0%) were complicated by pancreatic fistula in comparison to 3 cases (20%) had pancreatic fistula in group 2.

Conclusion: The modified technique of PJ using a second layer of “lesser omental pedicled patch” is easy and significantly decreases the pancreatic leakage and it is recommended to be used for PJ. Randomized large series will be needed to confirm the validity of these initial impressive results.

Biography:

Yoram Oron has completed his PhD from Hebrew University, Jerusalem and Post-doctoral studies from University of Virginia School of Medicine. He has taught Physiology and Pharmacology at Tel Aviv University (TAU), was a Department Chair, and TAU Director of International Academic Relations. His career included Visiting Associate Professorship at Cornell Medical School and numerous periods as Visiting Scientist at NIDDK, NIH. He has published more than 110 papers in reputed journals and has served as an Editorial Board Member of several journals. He is currently a TAU Professor Emeritus.

Abstract:

It is generally accepted that overexpression of plasminogen activator inhibitor 1 (PAI-1) correlates with worse prognosis and more invasive phenotype of many cancers, including pancreatic adenocarcinoma (PAC). We down-regulated PAI-1 expression in PANC-1 cells via shRNA knockdown (KD). The down-regulated variant (PD-PANC) exhibited neural morphological traits compared to cuboidal morphology of WT PANC-1s or vector-transfected cells. RT-PCR demonstrated that KD of PAI-1 leads to decreased expression of mesenchymal markers transcripts concurrently with increased expression of epithelial and neural transcripts, suggesting partial mesenchymal-to-epithelial transition. Importantly, PD-PANC1s expressed markedly more E-cadherin in a larger proportion of cells, whereas TUBB3 was expressed predominantly in cells with neural morphology. Despite this apparent more epithelial phenotype, PD-PANC-1s exhibited more invasive behavior in vitro. Although, the invading cells expressed more PAI-1 and less E-cadherin transcripts than non-invaders, it could not explain the observed increase in invasiveness. Using fluorescent supravital staining in a mixed vector/PD-PANC-1 population, we demonstrated that cells that down-regulated PAI-1 created environment promoting invasion of the few cells expressing high PAI-1 level. We previously reported that PD-PANCs exhibit higher uPA activity and continuously convert plasminogen to plasmin, which have been shown to activate matrix metalloproteinases. Indeed, inclusion of plasminogen enhanced invasion of PD-PANC-1s. In conclusion, our results suggest that fine balancing of different activities rather than extensive ablation of the “offending” PAI-1 protein maybe a better strategy in maintaining a less aggressive PAC phenotype.

Biography:

Prasad Pethe has completed his PhD from National Institute for Research in Reproductive Health (NIRRH) affiliated with University of Mumbai on differentiation of human embryonic stem cells into pancreatic lineage. Currently, he is an Assistant Professor at SVKM’s NMIMS School of Science in Mumbai and has experience of clinical and industry setup. He has published several papers in international peer reviewed journals of repute.

Abstract:

Differentiation of human embryonic stem cells (hES) involves interactions between various chromatin modifiers and signalling pathways. The sonic hedgehog (SHH) pathway plays an important role during development of foregut organs such as: liver, pancreas, stomach and intestines. Previous reports have shown that inhibition of SHH pathway is essential for formation of dorsal pancreas during embryonic development. Polycomb group (PcG) proteins BMI1 and EZH2 have been shown to be important for proliferation of pancreatic stem cells. Previous reports have shown that constitutive SHH signaling up regulates expression of BMI in medulloblastoma, pancreatic and breast cancer, leading to proliferation of cancer cells. Most research groups incorporate synthetic inhibitor of the SHH pathway during differentiation of hES cells into pancreatic lineage, but its effect on differentiation of hES cells into pancreatic lineage and expression of BMI1 has not yet been investigated. In the present study, hES cells were differentiated into pancreatic lineage in the presence and absence of SHH inhibitor. Western blot results showed that cyclopamine (SHH inhibitor) led to reduction in expression of sonic hedgehog, while the expression of PATCHED1, SMO and GLI3 by qRT-PCR indicated the inhibition of SHH pathway. BMI1 expression at both protein and transcript level, was directly affected by the sonic hedgehog pathway inhibition. However, expression of PDX1 (pancreas specific transcription factor) showed marginal reduction at protein and transcript level. The study shows the association between PcG protein BMI1 and sonic hedgehog pathway during differentiation of hES cells into pancreatic lineage in vitro.

Biography:

Daniel R Principe is a Medical student at the University of Illinois- College of Medicine and previously completed a Master’s degree in Biomedical Engineering at Northwestern University and a Bachelor’s degree in Biology at Loyola University Chicago. His research focuses on the role of Transforming Growth Factor β (TGFβ) in pancreatic and colon cancers, Pigment Epithelium-Derived Factor (PEDF) in pancreatic cancer, and the development of large animal models of carcinogenesis.

Abstract:

In early pancreatic carcinogenesis, TGFβ acts as a tumor suppressor due to its growth-inhibitory effects in epithelial cells. However, in advanced disease, TGFβ appears to promote tumor progression. Therefore, to better understand the contributions of TGFβ signaling to pancreatic carcinogenesis, we generated mouse models of pancreatic cancer with either epithelial or systemic TGFBR deficiency in a background with pancreas-specific expression of mutant KRAS, which is nearly uniformly expressed in pancreatic cancer patients. We found that epithelial suppression of TGFβ signals facilitated pancreatic tumorigenesis, whereas global loss of TGFβ signaling protected against tumor development via inhibition of tumor-associated fibrosis, stromal TGFβ1 production, and the resultant restoration of anti- tumor immune function. Similarly, TGFBR-deficient T cells resisted TGFβ-induced inactivation ex vivo. Adoptive transfer of TGFBR-deficient CD8+ T cells into a more aggressive model of mutant Kras-induced disease led to enhanced infiltration and granzyme B–mediated destruction of developing tumors. These findings paralleled our observations in human patients, where TGFβ expression correlated with increased fibrosis and associated negatively with expression of granzyme B. Collectively, our findings suggest that, despite opposing the proliferation of some epithelial cells, TGFβ may promote pancreatic cancer development by affecting stromal and hematopoietic cell function. Therefore, the use of TGFBR inhibition to target components of the tumor microenvironment warrants consideration as a potential therapy for pancreatic cancer, particularly in patients who have genetic deletion of tumor-suppressive TGFβ signals (i.e. DPC4/SMAD4) in the epithelium. While these patients are the most likely to benefit from TGFBR-inhibition therapy, there are many others in which TGFβ signaling is perturbed despite the presence of all its necessary components. Upon further investigation, we found that under normal conditions, tumor suppressive TGFβ signalling is highly dependent on the KRAS effector ERK. Yet this association was distinctly disrupted in human pancreatic cancer cells, and ERK opposes TGFβ-induced cell cycle arrest. Our data also suggests that such patients with intact TGFβ signaling may be highly susceptible to blockade of the MEK/ERK pathway, which restored normal tumor suppressive TGFβ signals and reversed EMT in human pancreatic cancer cells. These two unique approaches are tailored to molecular cancer subtypes, and are currently in preclinical trials in both mice and a yet unpublished transgenic porcine model of pancreatic cancer.

Biography:

Lorenzo Dioscoridi, after humanistic study, he successfully completed his Medical Schooling in Florence. He studied and worked at Karolinska University in Stockholm, at Karlova University in Prague and at Niguarda-Ca’ Granda Hospital in Milan. He is now working in Careggi Hospital (Florence) as resident of the last year at the Department of Surgery and Translational Medicine. He is Associate Editor of Pancreas Open Journal since 2015. He started to approach the laser technology since 2011. His main researches are about laser application on pancreatic and hepatic tissues. He is performing experimental studies using ND-YAG laser on pancreatic tissue to thermoablate tumours and cysts and using Holmium laser to destroy biliary stones in the common bile duct. He is using ND-YAG laser clinically to treat liver metastases and hepatocarcinoma.

Abstract:

Background: Pancreatic surgery is one of the most difficult and life-threatening surgery especially during necrotizing pancreatitis and solid neoplasm in advance stadium.

Aim of the study: To evaluate the possibility to use ECHO ND-YAG laser in pancreatic surgery and to establish the best power setting for the application on pancreatic tissue. We also consider two new points in our study: How the amylases content changes in pancreatic tissue treated with laser waves and what are the conditions of vessels walls in the heat damage area?

Methods: ECHO Laser ND-YAG 1064 nm, at the constant fluence of 1800 J/cm2 was used. The laser waves were inserted inside of the samples with optical fibers of 500 micron diameter for pre-established timing (11 min, 6 min and 4 min) in order to reach the constant fluence. Samples were then prepared for histological examination.

Results: At 3W power setting, the pancreatic tissue was not macroscopically modified except for increased cutting consistency. Histological examination showed no substantial microscopical differences in pancreatic cells that appeared only partially burnt (in fact, nuclei and membranes are still recognizable). The vessels in the surrounding area have the normal morphological aspects. At 5W, macroscopically the presence of an area, corresponding to the site of direct interaction of laser and tissue, completely burnt was found and the surrounding tissue did not appear substantially modified. Histological examination showed the complete absence of cells in the burnt area and an important heat damage of the surrounding cells till the 2nd centimeter from the site of laser application. The vessels in the heat damage area appeared completely coagulated. The enzymatic stain showed, At the power of 7 W , the burnt area was about twice than in the previous setting and histological examination showed the complete absence of cells in the burnt area and a larger heat damage of the nearest cells (till the 4th centimeter from the application site). The vessels in heat damage area were found completely coagulated.

Conclusions: A power setting between 4 and 6 W have been found as the best one for pancreas laser application because a complete destruction of the cells in the site of application but a limited heat damage in the surrounding healthy cells have been obtained. The study shows how laser waves destroy also amylases; that property in association with complete coagulation of small vessels in the heat damage area would reduce the damage of the rest of the organ and the risk of secondary bleeding.

Biography:

Amaresh K Ranjan is a Post-doctoral fellow at Icahn School of Medicine at Mount Sinai, New York, USA. He completed his PhD in 2011 from National Center for Cell Science, Pune India. His PhD work was related to vascular endothelial cell biology and diabetes. He has 12 publications in reputed journals and books. His publications have over 100 citations.

Abstract:

Vascular endothelial cell damage/dysfunction is known to be associated with the common etiology of morbidity and mortality in diabetic conditions. However, suitable markers of endothelial damage in diabetes are still required to be discovered. We studied endothelial damage in diabetes by using proteomics and genomics approaches. Human vascular endothelial cells were subjected to in vitro normoglycemia or hyperglycemia. Expression of endothelial specific genes responsible to regulate atherosclerosis, immune response, migration and adhesion were found affected in hyperglycemia. Proteomics studies by using 2D gel electrophoresis and tandem mass spectrometry indicated modulation of 12 new proteins including Hsp27b1, Macf1, Vim, Ckm, Tcp, Prv, Atm, Vinc, Smthln, Pmpcb, Nebl and Tcf20. Moreover, we observed higher transcript abundance of Hsp27b1, Hsp27b2, Ckm, Prv, Vinc, PMPCB and Tcf 20 in both type 1 and type 2 diabetic patients’ serum samples compared to that of non-diabetic (control) patients. We selected Hsp27b1, Hsp27b2 and Ckm to screen a larger cohort of diabetic patients (n=20) for their transcript abundance. Significantly higher transcript abundance of Hsp27b1 (p≤0.01) and Hsp27b2 (p≤0.001) along with CD133 (an endothelial specific marker) (p≤0.05) were observed in diabetic patients’ sera. Thus, our present study shows potential of hsp27b1, hsp27b2 and CD133 transcripts as a combinatorial biomarker of endothelial damage in diabetes. These biomarkers may help to detect or develop a therapy to reverse the pathophysiological changes responsible for secondary complications of diabetes.

Biography:

Howard J Leonhardt is a Biomedical Engineer Inventor with over 100 issued patent claims. In the 1980’s, he developed the leading predictably compliant cardiovascular balloon catheters and in 1990’s the leading stent graft system for repair of aortic aneurysms, the first percutaneous heart valve, stem cell and micro energy delivery catheters and the first intravascular lung and biological pacemaker. Since 1999, his research focus has been on Organ Regeneration. In early 2001, he led a team that completed the first-in-man non-surgical stem cell repair of a human heart. He has an honorary PhD in Biomedical Engineering from the University of Northern California. He graduated from the International Trade Program in 1982 from Anoka Technical College in Minneapolis, Minnesota and has attended certificate courses at the University of Minnesota and UCLA. He operates research labs in Northern and Southern California as well as in Utah and incubator/accelerators with over 30 startups in the current portfolio; 24 of those are organ regeneration focused bases on his own inventions.

Abstract:

Our team has developed a pancreas regeneration system with three major components. (1) A micro bioelectric regeneration stimulator that controls release of 10 regeneration promoting proteins including SDF-1 a stem cell homing signal, IGF-1, HGF, EGF, activin A+B, eNOS, VEGF, follistatin and tropoelastin. (2) A programmable, re-fillable micro infusion pump. (3) A proprietary fifteen component stem cell based regeneration composition comprised of a variety of cell types, growth factors, BMP-7, PDLI-1, HGH, selected alkaloids, micro RNAs, nutrient hydrogel, NADA and pancreatic matrix. The stimulator+pump is implanted just below the skin with a re-fillable silicone septum port with pacing infusion lead directed to the pancreas with a total conductive infusion wrap tip that is gentle on the pancreatic tissue. One portion of the lead is directed to the interior portion of the pancreas. Initial pilot translational study data will be presented as well as the anticipated upcoming clinical trial design.

Biography:

Zhaohui Xua has received his PhD in Pharmacognosy in 2000 and Fructus Arctii is the object of his Doctoral research topic. He has committed his research to the treatment of Fructus Arctii in type 2 diabetes for over 20 years. He has published nearly 20 papers on the anti-diabetic activity of Fructus Arctii. He has made a useful exploration of the material basis and mechanism of the anti-diabetic activity of Fructus Arctii.

Abstract:

Research Background: Fructus Arctii, called “Niubangzi” in China (Great burdock achene in English), is a well-known Chinese materia medica. It is the dried ripe fruit of Arctium lappa L. (family Asteraceae) and was included in the Chinese pharmacopoeia for its traditional therapeutic actions.

Aim of the study: To study antidiabetic activity and mechanism of total lignans from Fructus Arctii (TLFA) in KKAy mice, a spontaneous type 2 diabetic animal model.

Materials & Methods: TLFA was extracted from Fructus Arctii and purified as described previously. Male KKAy mice and C57BL/6J mice were used in this study, KKAy mice were gavaged once daily with either solvents (0.3% CMC-Na), TLFA (250 mg/kg), TLFA (125 mg/kg) or Metformin (200 mg/kg) for 11 weeks. Besides common evaluation indexes of antidiabetic activity such as blood glucose level, body weight, oral glucose tolerance test (OGTT), glycated hemoglobin, as well as lipid metabolism parameters in mice serum was analyzed. Histopathological examination of the pancreas, white adipose tissue, liver and skeletal muscle was performed by optical microscope. The gene expressions of protein tyrosine phosphatase 1B (PTP1B), leptin, adiponectin and glucose transporter type 4 (GLUT4) were determined by real-time PCR. The protein levels of the above molecules and PPAR-γ, ACC, p-ACC, AKT, phospho-Akt (p-Akt), AMPK, p-AMPK, insR and GSK3β were measured by Western blot.

Results: TLFA demonstrated significant hypoglycemic activity in KKAy mice and showed potential to inhibit weight gain. The

results of real-time PCR and Western blot showed that TLFA downregulated leptin, PTP1B while it upregulated adiponectin and GLUT4 (p<0.05). The protein level of AMPK, p-AMPK, GLUT4 and insR was also increased while the protein level of ACC, p-Akt, Akt was decreased (p< 0.05).

Conclusion: The results of this study indicate that TLFA has significant antidiabetic potential in KKAy mice. And this potential could be associated with activation of AMPK, insR and GLUT4 pathways and upregulated gene expression of adiponectin and GLUT4, with downregulation of Akt pathway and downregulated gene expression of leptin and PTP1B. It has a great potential to be further developed as a novel therapeutic agent for diabetes in humans.

Biography:

Daria Dranka-Bojarowska  graduated Silesian University School of Medicine in 2000. She is assistant in The Department of Gastrointestinal Surgery, Medical University of Silesia –a leader center of pancreatic surgery in Poland. She has completed her PhD in 2014 from Silesian University School of Medicine, She is author more than 20 medical articules and conferences abstracts. She has published 7 papers in reputed journals.

Abstract:

The aim of this study was a comparative analysis of the concentrations in serum of adipocytokines: adiponectin and leptin and CA 19-9 in patients with pancreatic cancer (PC), chronic pancreatitis (CP) and control group (CG). The study was performed in a group of 90 patients. The serum samples were taken from patients and the concentration of adiponectin, leptin, CA 19-9 and CEA were evaluated. The revealed concentrations levels of the adiponectin were significantly higher in the PC serum samples compared to the CP and CG. There was no significant correlation between increased adiponectin concentration and body fat mass in the PC group. The concentration of leptin was significantly lower in CP serum samples compared to PC and CG. The concentration of leptin was similar in the PC and CG. The concentration of leptin was mainly dependent on body fat mass and fat distribution. Additionally, measurement of waist circumference and body composition was recorded using bioelectrical impedance analysis. Significantly higher concentration levels of adiponectin in the PC group, independent of body fat mass, may play a potential role as a new tumor marker in PC and might be useful in the differential diagnosis between PC and CP. Author perform further investigation to validate this statement. To our knowledge, this was the first study evaluating not only BMI but also the content and distribution of body fat in patients with PC and CP.

Biography:

Albeit diagnosed and defined as a “sugar disease of the adult”; i.e., namely a disease of the carbohydrate metabolism by mostly authors; So called type 2 diabetes mellitus should be better defined as a “No Man’s Land” state of disease in adults, at most diagnosed by, in the majority of cases, a fasting glycemia equal or higher than 126 mg/dL. And Why That? Because in a global epidemic, which is badly out of control, there is not much time to lose. So let’s get into some facts! Despite all controversies surrounding the etiology, pathogenesis, and therapeutic roles for hyperglycemia in type 2 diabetes mellitus, newer anti-hyper-glycemic drugs are still getting onto the market at a high speed, due to the overconfidence in HbA1c as a surrogate outcome for micro-vascular complications; albeit. All large recent randomized clinical trials and meta-analysis have shown that trying to achieve glycemic levels close to the normal range did not reduce the most clinically important micro-vascular or macro-vascular hard endpoints as end-stage renal disease, vision loss, cardiovascular and total mortality, with the added harm of substantial increase in the number of hypoglycemic episodes, and even death rates. Is it not too soon for us to forget about the rosiglitazone saga? The above, among other core issues, will be covered in our talk.

Abstract:

Jose Mario F De Oliveira is an Associate Professor of Medicine in the Department of Medicine of Universidad Federal Fluminense, in the State of Rio de Janeiro, Brazil. He is also one of the Deputy Editors for Diabetes of The British Medical Journal. He has published a number of papers and served as a reviewer or author and co-author for many prestigious medical journals like “Hypertension”, “The American Journal of Hypertension”, “The Journal of the American Society of Nephrology”, “The British Medical Journal”, and the “New England Journal of Medicine”. His main interests are in the clinical research of diabetes and hypertension. He is a Certified Preventive Cardiologist, Nephrologist and Adult Intensive Care Unit Physician. Finally, he was a Post-Doctoral Clinical and Research Fellow at the Endocrinology-Hypertension-Diabetes Division of the Brigham & Women’s Hospital at Harvard Medical School, in Boston, USA and is one of the two authors of the recent electronic Diabetes e-book published and edited by The British Medical Journal for all doctors world-wide.

Biography:

Kunk completed medical school at the University of Tennessee in 2011 and internal medicine training at the University of Virginia in 2014.  He is currently Chief Fellow of Hematology-Oncology at the University of Virginia.  Active in the field of gastrointestinal malignancies, he received the Joesph H. Farrow Research Award to analyze the immune microenvironment of cholangiocarcinoma.  He has published more than 15 papers in reputable journals and presented at several national meetings.

Abstract:

Immunotherapy is an exciting and growing field.  It has caused a paradigm shift in the treatment of metastatic melanoma and its role in many other cancers is growing. With the explosion of novel immune targets, completed and ongoing clinical trials and exciting combination therapies, immunotherapy is becoming ubiquitous in the daily life of an oncologist. Yet pancreatic cancer remains a fatal cancer with few effective therapies. Pancreatic cancer has been considered as a disease that may not be amendable to immunotherapy given the paucity of infiltrating immune cells in the tumor microenvironment. However, mounting evidence suggests that the pancreatic immune microenvironment is more complex, involving cells and receptors that transform the pancreas from its normal architecture into a complex mix of suppressor immune cells and dense extracellular matrix that allows for the unrestricted growth of cancer cells. Despite early studies showing little to activity, more recent studies shown more promising results.

Biography:

Raji Sundararajan completed her PhD in EE from Arizona State University, USA and is serving as a Professor at Purdue University.  She has over 35 journal papers and 130 conference papers, and is the Editor of the book, Electroporation-based therapies for cancer: From Basics to Clinical Applications.  She is a reviewer of electroporation proposals of various governmental agencies, including NIH of USA and Ireland.  She is also a sought-after reviewer of a number of scholarly journals and member of Editorial boards of repute.

Abstract:

With ~40,000 deaths per year out of ~46,000 incidences in the US, pancreatic cancers is one of the deadliest cancers.  It is the 4^th leading cause of death for both men and women and one in 4 deaths in the US is due to it.  Pancreatic adenocarcinoma (PAC) is the most common (90%) pancreatic cancer.  Pancreatic surgery involves removal of head or that part of the pancreas, where the tumor occurred, lymph nodes draining that part, part of bile duct, gall bladder and part of small bowel-at the least.  Total pancreatectomy involves the removal of the whole pancreas, spleen, and the rest of parts as above.  All these lead to poor quality of life with enormous pain and suffering.  In addition, only 20% of the pancreatic tumors are removed by surgery.  Both stages III and IV cancers and metastatic tumors cannot be removed by surgery.

Chemotherapy is not that efficient for the pancreatic tumors due to resistance to drug by most of the pancreatic cell lines.  Radiation is not used much due to the proximity of nearby major vessels and organs.

This indicates that the current standard treatments are inadequate and there is an urgent and critical need for effective alternate therapies.  Towards this we propose the administration of electrochemotherapy to arrest the uncontrolled growth of pancreatic cancer cells.  This technique involves enhanced uptake of chemodrugs due to the opening of pores, caused by the electrical pulses, allowing generally impermeable or less permeable chemo drug molecules to enter into the cells.  A number of cancers have been successfully treated using this technique and we studied its efficacy for pancreatic cancer.  For this purpose, both Panc-1 and Pance-28 cell lines were studied.  The chemo drug used was Gemcitabine at a concentration of 100µM.  Both high intensity, short duration pulses (1200V/cm, 100µs, 8 pulses at one second interval) and low intensity, long duration (500V/cm, 1, 10, 20 and 25ms pulses) were studied.  The results indicate that reduced viability, as low as 13% were obtained using this technique for Panc-28 cells.  The lowest viability was 31% in the case of panc-1 cells.  The corresponding viability using drug only is 60% or above, for both cell lines.  This indicates the efficacy of electrochemotherapy in treating the PAC cells effectively using the synergy effects of both the drug and the electrical pulses to enhance their uptake.  This technique shows enormous potential to be transferred to the clinics.

Biography:

Zeng has completed his PhD at the age of 30 years from Harbin Medical University. He is the vice director of General Surgery in the 2nd affiliated hospital of Harbin Medical University.

Abstract:

Pancreatic fistula (PF) is the most serious complication after pancreaticoduodenectomy (PD). Numerous techniques have been developed to treat PF, although none has effectively reduced its rate. Herein, we report our preliminary experience using a new technique known as pancreaticojejunostomy (PJ).

Methods: Twenty-two patients underwent PD for the treatment of neoplasms, with end-to-side sealing PJ in combination with duct-parenchyma-to-mucosa-seromuscular one-layer anastomosis, between January 2014 and March 2014. The postoperative outcomes of the patients were analyzed.

Results: The mean time of the PJ procedure was 18.5 min (range 12-30 min). One patient exhibited a grade A PF (4.5%). Three patients developed other complications, including a surgical site infection, pneumonia and a gastric stress ulcer with bleeding. The overall morbidity rate was 18.2%. There were no operative or hospital deaths.

Conclusion: This novel PJ technique was easy to perform and reliable, and it significantly reduced the occurrence of postoperative PF. Notably, this approach can be applied for any size duct and any consistency of pancreas

Biography:

G. Roeyen is senior staff member,  department of Hepatobiliary, Endocrine and Transplantation Surgery at the Antwerp University Hospital. Recently a paper on pancreatogenic diabetes in patients referred for pancreatic surgery has been published in ‘Pancreatology’

Abstract:

Objective:

Recently, pancreaticogastrostomy (PG) regained interest as reconstruction technique after pancreaticoduodenectomy (PD) because this technique might imply a lower risk of clinical pancreatic fistula than reconstruction by pancreaticojejunostomy (PJ). We hypothesize that PEI (pancreatic exocrine insufficiency) is more common during clinical follow up after PG than after PJ.

Research Design and Methods:

This study compares the prevalence of PEI in patients undergoing PD for malignancy reconstructed by PG versus reconstruction by PJ. PEI during the first year of follow up was defined as intake of pancreatic enzyme replacement therapy (PERT) within 1 year postoperatively and / or an abnormal exocrine function test.

Results:

In total 186 patients operated at 2 University Hospitals, were included. PEI during the first year postoperatively was present in 75.0% of the patients with PG compared with 45.7% with PJ (p<0.001). Intake of PERT within 1 year after surgery is more prevalent in the PG group: 75.8% versus 38.5% (p<0.001). There was a trend towards more disturbed exocrine function tests after PG (p=0.061). 

Conclusions:

PEI is more common with PG than with PJ reconstruction after pancreaticoduodenectomy for malignancy.

Biography:

Naomi Walsh completed her PhD in Dublin City University, Dublin Ireland, a holds a Masters of Public Health (MPH) from University College Dublin, Ireland. She conducted her post-doctoral research as a Cancer Prevention Fellow at the National Cancer Institute, USA. She is currently a Health Research Board/Irish Cancer Society Cancer Prevention Fellow in the National Institute for Cellular Biotechnology, DCU, Ireland. She has published extensively in the area of pancreatic cancer, and has 12 first author journal publications. She serves as a committee member for the Irish Association for Cancer Research (IACR).

Abstract:

Pancreatic cancer is a devastating disease. The lethality of pancreatic cancer is related to its rapid growth and tendency to invade adjacent organs and metastasise at an early stage. Identification of targets which play a role in the highly invasive phenotype of pancreatic cancer may help to better understand the biological behaviour and the rapid progression of this cancer. A systematic evaluation of miRNA and mRNA expression profiling was performed in highly invasive and non-invasive sub-clones derived from the MiaPaCa-2 cell line. Differential expression between the highly invasive and non-invasive clones revealed 522 genes and 12 miRNAs altered (p<0.05; fold change > 2). The integrated analysis of miRNA:mRNA found significant anti-correlation with 11 genes co-regulated by eight miRs. Validation of the miRNA:mRNA interactions was performed in seven pancreatic cancer cell lines and corresponded with invasive capabilities. Furthermore, expression of 4 miRs (mir-9, mir-135b, mir-148a and let-7c) was independently established in 20 pancreatic cancer and adjacent normal tissue specimens. Functional miR-gene targeting was validated in primary cell lines (n=4) derived from pancreatic tissue and established pancreatic cancer cell lines. Let-7c was found to be down-regulated in highly invasive cell lines and lowly expressed in pancreatic tumour tissue. Let-7c negatively regulates SOX13 expression. SOX13 is a direct target of SHH signalling and RNAi knockdown of SOX13 reduced proliferation and invasion of pancreatic cancer cells. The identification of key miRNA:mRNA gene interactions and networks provide potential diagnostic and therapeutic strategies for better treatment options for pancreatic cancer patients.

Biography:

Mark Podberezin has completed his MD and PhD degrees, as well as Clinical Hematology Fellowship, from National Hematology Center in Moscow, Russia. He did his Anatomic and Clinical Pathology Residency training from the University of Illinois at Chicago and Hematopathology Fellowship from Texas Methodist Hospital in Houston, TX. He has published 14 papers and has presented many at national as well as international conferences.

Abstract:

Pancreas can be involved in about 30-40% of patients with non-Hodgkin lymphoma. However, primary pancreatic lymphomas (PPL) are exquisitely rare and comprise less than 1% of extranodal lymphomas and approximately 0.5% of all pancreatic malignancies. PPLs are most commonly located in head of the pancreas and, therefore, they can present with symptoms similar to those of pancreatic adenocarcinomas, i.e. abdominal pain, jaundice, and weight loss. Invasive tumor growth not respecting anatomic boundaries, as well as absence of significant dilatation of main pancreatic duct, raise degree of suspicion for PPL rather than adenocarcinoma. However, systemic and extra-pancreatic lymphomas, with involvement of pancreas, are much more common than PPLs. We observed a case of 78 y/o man who presented with rapidly progressive weight loss and jaundice. CT scan demonstrated ill-defined lesion in pancreatic head, 2 cm in size, with massive peripancreatic lymphadenopathy and 6 cm splenic mass. Core needle biopsy led to the diagnosis of high grade diffuse large B-cell lymphoma (DLBCL). Patient’s status progressively deteriorated, and he expired before initiation of chemotherapy. Autopsy demonstrated involvement of pancreas, spleen, and peripancreatic lymph nodes by lymphoma. However, due to presence of splenic involvement, with dominant mass in the spleen, DLBCL of spleen with secondary pancreatic involvement was diagnosed. Diagnostic criteria, which favor PPL, vs. secondary pancreatic involvement by lymphoma, are following: No superficial or mediastinal lymphadenopathy; Normal leukocyte count; Main mass in the pancreas with lymph node involvement confined to peripancreatic region; and no hepatic or splenic involvement.

Biography:

Christine Mehner has completed her MD at the University of Witten/Herdecke, Germany and became a Post-doctoral fellow at the Mayo Clinic Cancer Center, Jacksonville, FL. She has published multiple first author papers in the field of cancer research, in reputed journals that have been recognized by the Faculty of 1000 and have been featured in news and media. She has been serving as an Editorial Board Member and constant reviewer for various journals.

Abstract:

Pancreatic ductal adenocarcinoma (PDA) arises at the convergence of genetic alterations in KRAS with a fostering microenvironment shaped by immune cell influx and fibrotic changes; identification of the earliest tumorigenic molecular mediators evokes the proverbial chicken and egg problem. Matrix metalloproteinases (MMP) are key drivers of tumor progression that originate primarily from stromal cells activated by the developing tumor. Here, MMP3, known to be expressed in PDA, was found to be associated with expression of Rac1b, a tumorigenic splice isoform of Rac1, in all stages of pancreatic cancer. Using a large cohort of human PDA tissue biopsies specimens, both MMP3 and Rac1b are expressed in PDA cells, that the expression levels of the two markers are highly correlated, and that the subcellular distribution of Rac1b in PDA is significantly associated with patient outcome. Using transgenic mouse models, coexpression of MMP3 with activated KRAS in pancreatic acinar cells stimulates metaplasia and immune cell infiltration, priming the stromal microenvironment for early tumor development. Finally, exposure of cultured pancreatic cancer cells to recombinant MMP3 stimulates expression of Rac1b, increases cellular invasiveness, and activation of tumorigenic transcriptional profiles. Implications: MMP3 acts as a co-conspirator of oncogenic KRAS in pancreatic cancer tumorigenesis and progression, both through Rac1b-mediated phenotypic control of pancreatic cancer cells themselves, and by giving rise to the tumorigenic microenvironment; these findings also point to inhibition of this pathway as a potential therapeutic strategy for pancreatic cancer.

Biography:

Chrystal U Louis has 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 from 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. She has 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, longterm 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 of and specificity 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.

Biography:

Abstract:

Biography:

Murat Acar has graduated from Istanbul University, Cerrahpasa Medical Faculty in 1996. He then completed his residency education in 2001. He worked as a research fellow at Department of Abdominal-Interventional Radiology, Brigham &Women’s Hospital, Harvard University between 2007-2008. Recently, he continued to work as a Consultant and Professor of Radiology at Department of Radiology, King Hamad University, Bahrain. His special interests are Abdominal Imaging and Non-vascular Intervention.

Abstract:

Detection of the pancreatic cystic lesions highly increased mainly due to incredible progress in the cross-sectional imaging availability and technological improvement. Increasing of detection of this lesions resulted with significantly rise in the number of surgical resections. But, resection of these lesions could be unjustified due to benign nature of many cystic lesions. Thus, it is crucial to make a correct differential diagnosis to avoid unnecessary surgeries, besides the detection of these lesions. Fortunately, most of the pancreatic cystic lesions have either characteristic imaging features or typical age and gender predominance. Radiologists also should be sufficiently aware of management of cystic lesions. Close cooperation of radiologist with surgeons and gastroenterologist also will be effective in terms of accurately diagnosis and management of the patient and it will allow avoiding from unnecessary invasive procedures or surgical interventions. In this review, we discuss briefly clinical presentations, characteristic features, differential diagnosis with a wide range of interesting cases and lastly management of the patients.