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Dr. Nishino is currently working as gastroenterologist at Southern TOHOKU General Hospital. Dr. Nishino graduated Jichi Medical University in 1987. He then worked at Southern TOHOKU General Hospital as director of gastroenterology. He has authored several publications in various journals and books. His publications reflect his research interests in pancreaticobiliary disease and diagnosis by Abdominal xerography. Dr. Nishino is serving as a fellow in The Japanese Society of Gastroenterology, Japan Gastroenterological Endoscopy Society, The Japanese Biliary Association.
ERCP requires delicate and sophisticated manipulation to perform, moreover secure and fair procedure without complication of pancreatitis. Our mission to lead ERCP is to perform perfectly. Although there is no answer to make it possible yet.
Now wire guided cannulation (WGC) is the current standard strategy to perform ERCP. However WGC could not even make it possible, it is a blind technique, the rates of successful access to bile duct (BD) estimate up to 90-95% on some Randomized studies. The difficult cases of ERCP as rest 5-10% still remained unknown.
We evaluate the cause of difficulty to access BD. We here present the superiority of contrast-assisted cannulation (CAC). Visualized images of the intra-ampullary anatomy reveal the causes for any difficulties to access BD.
In our hospital, we perform every ERCP with CAC, and evaluate accessibility to the BD inspiring both ampullary morphology and intra-ampullary biliary anatomy. We are able to observe unusual pathways, and we demonstrate how to access the BD using an original ‘sawing technique’, which refers to delicate and progressive manipulation using a catheter only, without a guide wire (GW). Co-ordinated manipulation of a scope with a catheter could make passing through unusual bifurcations and difficult angles possible.
Out of a total of 4039 cases over a 13-year period in our facility, 2177 were naïve papilla. The success rate in accessing the BD was 97.9%, and 1.6% of the naïve papilla cases had post-ERCP pancreatitis. In the naïve papilla cases, we evaluated the difficulty of cannulation, taking three factors into consideration. First is whether the papilla has an ovoid appearance similar in shape to a ‘long nose’. Second is the angle; whether the intra-ampullary BD rises perpendicularly from the pancreatic duct. The final factor is the presence or absence of tiny cysts within the papilla.
This article is not basic and foundamental but essential and universal. The anatomy of intra-ampulla has many variations; therefore, we have to respond flexibly to adapt to these variations. Contrast medium will always visualize all possible routes to the BD; however, it can be difficult to follow these routes. Therefore, CAC is a superior strategy to WGC in terms of safety and reliability when performing ERCP.
Lim Yoon Pin is currently working as an Assistant Professor at National University of Singapore. He is a Principal Investigator and Heads the Laboratory of Molecular and Translational Cancer Research at the Yong Loo Lin School of Medicine. He has completed his PhD from the Institute of Molecular and Cell Biology, Singapore. His current interest is the translation of the understanding of the oncogenic function, mode of action and regulation of WBP2 in epithelial cancers from bench to bedside including molecular diagnostics and targeted therapeutics.
Total sales of oncology drugs in 2017 was >USD50 billion and Herceptin was the 3rd top selling drug with about USD7 billion sales. Her2+ breast cancer is forecasted as the highest-growing segment of breast cancer treatment market to increase by 2.5 fold by 2023. Herceptin has a compound annual growth rate of 9.88% going from $4.95 billion in 2013 to $12.7 billion in 2023. While Trastuzumab-based chemotherapy has shown remarkable clinical benefits for HER2-positive breast cancer patients, a subset of patients (30-40%) shows little or no effect. This highlights an important clinical need for biomarkers in addition to Her2 for better stratification of patients for precision medicine of Her2+ breast cancer. Her2+ breast cancer is associated with an amplification of the HER2 locus in chromosome 17q. We hypothesized that HER2 and its co-amplified genes in C17q not only form a molecular network but also cooperatively and functionally contribute to the phenotype of Her2+ breast cancer. In other words, the Her2-associated genes may regulate the response of Her2+ breast cancer to drugs and are therefore potential companion diagnostics for HER2-based therapeutics. To this end, my lab has created an in silico network of genes in C17q that are co-amplified with Her2 in breast cancer. In my talk, I will describe a recent multi-center, cross border retrospective proof-of- concept study, which establishes that women who are <50 years and with Her2-positive breast cancers that overexpressed a Her2-associated gene (WBP2) had better pathologic complete response to Trastuzumab-based neoadjuvant therapy of 78% compared to 40% in non-stratified Her2-positive breast cancer. The findings allow clinicians to better plan therapeutic interventions for patients. Being able to predict which patients would attain successful downstaging of their tumors from neoadjuvant therapy would also guide surgical decisions e.g. breast conserving surgery versus mastectomy. Consequently, this would improve the overall patients’ outcome.
Jianhua Luo has been studying Molecular Pathology related to human malignancies since the last 24 years. Currently, he is a Professor of Pathology and Director of High Throughput Genome Center at University of Pittsburgh. In the last 16 years, he has been largely focusing on genetic and molecular mechanism of human prostate and hepatocellular carcinomas. In this period, his group has identified and characterized several genes that are related to prostate cancer and hepatocellular carcinoma, including SAPC, myopodin, CSR1, GPx3, ITGA7, MCM7, MT1h and GPC3. He has characterized several signaling pathways that play critical role in prostate cancer development, including Myopodin-ILK-MCM7 inhibitory signaling, myopodin-zyxin motility inhibition pathway, CSR1-CPSF3, CSR1- SF3A3 and CSR1-XIAP apoptotic pathways, MT1h-EHMT1 egigenomic signaling, ITGA7-HtrA2 tumor suppression pathway, GPx3-PIG3 cell death pathway, AR-MCM7 and MCM7-SF3B3 oncogenic pathways. He proposed prostate cancer field effect in 2002. He is one of the pioneers in utilizing high throughput gene expression and genome analyses to analyze field effects in prostate cancer and liver cancer. He is also the first in using methylation array and whole genome methylation sequencing to analyze prostate cancer. Recently, his group found that patterns of copy number variants of certain specific genome loci are predictive of prostate cancer clinical outcomes, regardless of tissue origin. His discovery of several novel fusion transcripts and their association with aggressive prostate cancer has brought significant new insight into the field of prostate cancer research. Overall, these findings advance our understanding on how cancer develops and behave, and lay down the foundation for better future diagnosis and treatment of human malignancies.
Accurate prediction of prostate cancer clinical courses remains elusive. In recent studies, we performed whole genome analysis on prostate cancers by combining Affymetrix SNP6.0 chip, whole genome sequencing and transcriptome sequencing. Our results showed that combination of genome copy number variance and novel fusion transcripts specific for cancer achieved high accuracy in predicting prostate cancer outcomes. The prediction model was further improved when these molecular criteria were combined with Nomogram or Gleason’s grading. Interestingly, some of these fusion genes are also present in a variety of human malignancies. One of these fusion genes, MAN2A1-FER appears a cancer driver since it induced cancer both in vivo and in vitro. Treatment of cancers with drugs specific for MAN2A1-FER signaling pathway produced dramatic improvement of metastasis and survival rate of animals xenografted with cancers positive for this fusion gene. Our analyses suggest that targeting therapy for fusion genes holds promise as an effective treatment for human cancers.
Dr. Ali Ghrebawi has vast 20 years’ experience in the field of General Surgery, Digestive Surgery and Proctology. He was worked within the last 15 years in Germany as General & Digestive surgeon and as Head of Coloproctology department at Ludmillenstift Hospital in Germany. He was also the Chief of Digestive surgery at the Coloproctology center in Germany.
Dr. Ali’s areas of expertise include Laparoscopic dealing with the colorectal diseases such as cancers & rectum prolapse, Lap Sleeve operations, Proctology, Hiatus Hernia and all other kinds of Hernia.
Most surgeons are now convinced of the benefits of the laparoscopic approach in colorectal surgery. The laparoscopic approach for benign and malignant colon disease is safe, feasible, and effective. More challenging is the adoption of this approach while addressing colorectal cancer disease and maintaining oncological principles. After performing a standard laparoscopic surgery technique in benign and malignant diseases for several years, we are now moving one step forward.
Oral Session 1:
- Diagnosis & Advanced Treatments
Assoc Prof Dr. Christina Nasadyuk
Danylo Halytsky Lviv National Medical University Biochemistry, Ukraine
Title: The cytoprotective effect of the tripeptides h-glu-asp-gly-oh and h-lys-glu-asp-oh in indomethacin-induced enteropathy in rats
Christina Nasadyuk is a physician, researcher and academic teacher with a PhD degree in Medical Biochemistry. Her current research is focused on the evaluation of the glycomic changes in gastrointestinal disorders as well as the role of cyclooxygenases, lipoxygenases, antioxidant and nitric oxide system in the processes of cytoprotection and ulceration of the stomach mucosa and the search for new gastroprotective peptides. The research is aimed at the reduction of NSAIDs gastrotoxicity. Has also scientific and management experience in cord blood banking industry, having contributed to its shaping and development in Ukraine.
Introduction. Nonsteroidal antiinflammatory drugs (NSAIDs) remain the most widely prescribed medications worldwide. Despite generally accepted strategies to reduce the side effects of these drugs towards stomach mucosa, there is increasing evidence that enteric mucosa is also susceptible to NSAIDs toxicity. However, uptodate medicine provides limited options for small intestine protection in chronic NSAIDs users. Short peptides were repeatedly reported to be promising agents for gastroprotective purposes [1,2].Aim of research was to assess the effect of H-Glu-Asp-Gly-OH and H-Lys-Glu-Asp-OH on NO-synthases (NOS) activity and lipid peroxidation processes in small intestinal mucosa (SIM).
Material and methods. Studies were conducted on white male rats, devided into 4 groups (n=6 per group): 1) controlÍ¾ 2) intragastrically (ig) administered indomethacin (IND), 10 mg/kgÍ¾ 3-4) ig pretreated with H-Glu-Asp-Gly-OH and H-Lys-Glu-Asp-OH (10µg) ig 30 min before IND introduction. 24h later rats were sacrificed, small intestine was isolated, washed with saline, exposed to gross inspection and in SIM homogenates NOS activity and MDA content were determined. In blood plasma L-arginine concentration was measured.
Results. Gross inspection of SIM did not reveal any visible lesions in experimental animals. However, biochemical investigations of SIM homogenates revealed that nonselective cyclooxygenase (COX)-1/COX-2 blockage with IND caused the development of nitrosooxidative stress. In SIM of IND-treated rats the increase of activities of NOS (28%, p<0.05) and iNOS (35%, p<0.05) was revealed, cNOS activity had tendency to decrease and L-arginine concentration in plasma decreased by 40% (p<0.05) compared to control group. MDA content increased by 35% (p<0.05) compared to control animals. In H-Lys-Glu-Asp-OH-pretreated rats iNOS activity decreased by 26% (p<0.05) in SIM and L-arginine concentartion in plasma increased by 27% (p<0.05) compared to the effect of IND. Pretreatment with H-Glu-Asp-Gly-OH did not cause any statistically significant difference in nitrosooxidative stress indices in SIM and blood plasma, however a tendency to decrease of iNOS activity in SIM, compared to isolated effect of IND, was noted.
Conclusions. Nonselectice COX-1/-2 blockage with IND causes nitrosooxidative stress in SIM. Tripeptide H-Lys-Glu-Asp-OH reversed pathobiochemical changes in SIM, induced by COX-1/COX-2 blockage and its molecular mechanism of action needs further elucidation.
Title: Non medical characterization of orgasm associated with approach sex can last up to 20 seconds to 15 minutes, eligible women individuals high side transportation facility of Private Pharmacy Institutions in Pune, India.
Dr. Rahul Hajare has been a hard worker all his academic life. After his Ph.D in Pharmacy from VMRF Salem which he completed with flying colours, he is fortunate to work NARI primer HIV research Institute to complete Post Docunder the of World Renowned Scientist Respected Dr. R.S.Paranjape., Retired Director & Scientist ‘G’ National AIDS Research Institute Pune. Dr. Rahul Hajare has Associate Professor of Pharmaceutical Medical Chemistry to Pune University (until 2020), he has serviced three times AssociateProfessor in Pharmaceutical Science and Analytical Science. Graduated from Amravati University in 2003, after an assignment he worked as an M.Pharm Scholar in the Institute of Pharmaceutical Education and Research passed with distinction, he has Post Graduate Teacher for Master of Pharmacy, he has more than 30 scientific and methodological works, 3 patents of scientific research. Dr. Rahul Hajare now Principal of Ishwar Deshmukh Institute of Pharmacy affiliated combined Amravati University and All India Council of Technical education New Delhi.
Face index and penetrative sex is not the only path to orgasm. Even non-genital stimulation, like kissing, petting, or nipple play can do the trick. Whether you have in a new relationship, on your honeymoon or approaching the 10-year mark of marriage, having a good sex life takes a deep intimacy that goes beyond the physical. Having good sex means knowing how your partner's body works and what he needs. It means knowing your own needs, and owning your sexuality and pleasure! What better way to do this than by discovering new, interesting facts about female orgasms, right? These interesting facts about female orgasms will make sex with your partner feel new again. 70 per cent of female orgasms are clitoral in origin. Because the clitoris has over 8,000 nerve endings, it's no wonder that clitoral stimulation is responsible for most female orgasms. While clitoral orgasms happen more than vaginal orgasms for most women, it is possible to have both. This is what is known as a blended orgasm. This climax combo can be achieved through certain positions, such as lying on your back with feet dangling over the edge of the bed. Then, raise your pelvis during sex, as your partner reaches in to stimulate your clitoris.
Title: Maintrac - A new clinical method for quantitative CTC diagnostic, treatment selection, monitoring and surveillance of patients
Martin Burow has completed his Chemistry and Biochemistry PhD at the University of Münster in 1993 and worked 3 years as a Post-doctoral fellow for the Ministry of International Trade and Industry at the National Institute of Materials and Chemical Research (NIMC) in Tsukuba, Japan. After his return to Germany, he started his career in the medical device industry and developed the Asian-Pacific markets for Brahms-Thermofisher in the field of Medical Diagnostics (thyroid, sepsis, prenatal and oncology). Later, he started his own company (DMB-Diagnostics GmbH) to introduce highly innovative diagnostics worldwide for better treatment standards of oncological patients.
Maintrac® is a laboratory based method to quantify in a reproducible manner living circulating tumor cells. This way it is possible to do further analytic with these cells. Be it molecular genetic testing of certain tumor characteristics or surface protein determination for real pharmaceutical target identification. Since these CTCs are alive it is possible to check all different chemotherapeutics and their killing rate on these CTCs. Best working medications can be selected before starting aggressive chemotherapies. Furthermore it is possible to monitor treatment success “just” by quantifying CTC over the cause of the therapy. Even during and after endocrine therapy it is possible to show how long to give i.e. Tamoxifen or when to switch to other, more efficient medication in case the cell number is increasing. This method was developed over the last decade and works on all tumors deriving from epithelial origin (almost all solid tumors). We showed in several clinical trials with > 650 patients and > 100,000 measurement significant improvement for patients and the overall relapse free survival while being monitored and treated based on this method. Maintrac is nowadays already used in clinical routine in ~30 countries worldwide.
Mitchell S Albert is a Research Chair at the Thunder Bay Regional Research Institute and a professor at Lakehead University.At the Thunder Bay Regional Research Institute, he is the Director of MRI Research, Director of the Hyperpolarized Gas MRI Laboratory, and a Scientist. At Lakehead University, he is a Professor in Chemistry and an Adjunct Professor in biology, physics, and the health sciences. Prior to this, he was Associate Professor of Radiology at the Harvard Medical School. He is one of the inventors and pioneers of hyperpolarized gas MRI, and holds 9 patents on its development. He received the United States Presidential Award from President Clinton for this invention and received a CAREER award from the National Science Foundation (NSF). a
Hyperpolarized (HP) agents have the potential to vastly improve MRI sensitivity for the diagnosis and management of many diseases. The hyperpolarization of xenon (129Xe) can result in an enhanced signal by a factor of up to 100,000, which enables direct detection of the HP agent with no background signal. HP 129Xe is a potentially valuable MR tracer for functional imaging due to its high solubility in the blood and brain, and its large chemical shift range. HP 129Xe can also be used withbiosensors for molecular MR imaging using the hyperpolarized xenon chemical exchange saturation transfer (HyperCEST) technique which allows the detection of probes at as low as femtomolar concentrations. HP 129Xe can be delivered to a target by means of dedicated molecular cage systems that can encapsulate xenon and bind to biological sites of interest using a targeting moiety, such as an antibody or a ligand, which enables detection of a specific biomarker. We have obtained the worlds first in vivo HyperCEST image via intravenous injection in a rat, which clearly illustrates the kidneys.
Trevor G Marshall graduated from the University of Adelaide, South Australia, in 1974. He taught at the Institute of Technology in Lae, Papua New Guinea, Curtin University and the University of Western Australia, before moving to California in 1982. His Doctoral thesis, ‘Insulin metabolism in Diabetes’, was accepted by the University of Western Australia in 1985. He is currently Director of the Autoimmunity Research Foundation in California. He has won US FDA Rare Disease Designations for minocycline and clindamycin in the treatment of sarcoidosis. He is a Fellow of the European Association for Predictive, Preventive and Personalised Medicine (Brussels) and a member of the International Expert Council, Community of Practice: Preventative Medicine (Moscow).
Human biology, or at least the understanding of the complexity of human biology, has exponentiated since the turn of the century. Previously it was thought that the human Genome, or at least its Transcriptome subset, expressed around 20,000 proteins. Yet the Human Proteome is currently estimated to be between 250,000 and 1 million proteins. Add to that the 42,000 components of the human Metabolome which have already been identified, and the process of identifying clinically useful biomarkers is becoming very difficult indeed. Our focus has been on yet another level of complexity, the Microbiome, understanding its biomarker contribution by both transcriptional and post-translational mechanisms. While studying the action of microbiome components on the VDR Nuclear Receptor we came to realize that the biomarkers loosely called “Vitamin D” were actually steroid transcriptional-factors, rather than “vitamins.” When we published this it seemed as though the whole world had descended on our shoulders. Clinical Medicine just didn’t want to know that what it thought was a biomarker for health was actually a biomarker for disease. Even today, now that the prosective studies are coming in, few appreciate the complexity of properly interpreting the “Vitamin D” biomarkers. Here we propose that TNF-alpha is also a compromized biomarker. The discovery that TNF-alpha release in the spleen is controlled primarily by the brain, and that brain immune activity is affected by the electrosmog which nowadays surrounds us, necessarily changes the way that this biomarker needs to be studied and interpreted.
Claude Prigent is a Director of Research, CNRS and Head of the Cell Cycle team, IGDR. He has been elected as an Associate Professor at the University Laval, Quebec, Canada. After completing his post-doc in the DNA repair filed under the direction of Thomas Lindahl at the ICRF in London he has been working on mitosis trying to understand how this cell cycle stage was control by phosphorylation. He focused his activity on the Aurora-A kinase and cancer.
Aurora-A serine threonine kinase is a key player in cell cycle controls and essential for the progression through mitosis. It was found over-expressed in many human cancers. A gain of activity was proved to favour chromosome instability and carcinogenesis in mice. More importantly its over-expression was also reported to lead to resistance to drugs such as microtubule poisons used in chemotherapy. Additionally a loss of Aurora-A activity leads to uncontrolled stem cells proliferation at the origin of cancers in Drosophila and presumably in mice too. Aurora-A kinase has been a priority target for the development of inhibitors to be used in cancer treatment. Using a chemical-genetic approach, we investigated the effects of a specific inhibition of Aurora-A kinase during cell cycle progression, in particular during mitosis, in normal conditions but also in the presence of taxol or nocodazole. At the contrary to previous reports, we found that Aurora-A kinase activity was essential to arrest the cells in mitosis in response to taxol or nocodazol. An inhibition of Aurora-A in the presence of these drugs clearly leads to abortive mitosis and formation of polyploidy cells.