The greatest current and future challenge is how to translate the revolution in biomedical research with next-generation sequencing (NGS) technologies and new methods exploring regulatory networks into Clinical Oncology. This strategy is the most rational approach to overcome unmet needs of therapeutic resistance, recurrence and death. Methods Valid published data, usually in top journals, on genome analysis of clinical samples were reviewed. Genomic studies are distinguished in two classes. Conventional, static single-biopsy analyses with whole-exome sequencing (WES), whole-genome sequencing (WGS) and RNA-sequencing (RNA-seq) can reveal structural and functional coding and noncoding mutational landscape. On the other hand, breakthrough genome studies applying NGS systems can evaluate genomic clonal evolution in time and space. Identification of intratumor heterogeneity (ITH) with multi-regional NGS (MR-NGS) before and after systemic therapy, as well as the detection of circulating genomic subclones (cGSs) with serial circulating cell-free DNA followed by NGS (cfDNA-NGS), could overcome intrinsic and acquired therapeutic resistance and, possibly, disease relapse. Results Large-scale NGS analyses of a single biopsy have already identified valid novel cancer driver genes, molecular classifications, druggable mutations and functional-noncoding regulatory alterations. Breakthrough analyses of multiple tumoral and liquid biopsies at different time points have demonstrated extensive ITH and different genomic characteristics after systemic treatment. Serial cfDNA-NGS has provided the opportunity for patient monitoring and early prediction of recurrence before clinical diagnosis. Interpretation I will present two future strategic targets. First, the innovative design of clinico-genomic trials to validate the promising published data on molecular classifications and novel druggable mutations. Moreover, ITH and serial cGSs offer the capacity to predict therapeutic response and guide decision-making on effective treatment with available and novel targeted drugs. These patient-centric genomic trials shape the roadmap of Cancer Precision Medicine. Second, in a long-term horizon, identification of functional non-coding alterations in transcription factor binding sites represents the basis of understanding, predicting and targeting of dynamic transcriptional networks with innovative agents. Ultimately, intra-patient heterogeneity, including all structural and functional coding and non-coding alterations, will lead to comprehensive clinical Precision Oncology
Dimitrios H. Roukos, MD, PhD, is Professor of Surgery – Precision Cancer Medicine and Founding director of “Centre for Biosystems and Genome Network Medicine” in the Ioannina University, School of Medicine. His translational and clinical research from traditional and single gene investigation to molecular networks and clinical cancer genome NGS analysis has been recognized by international scientific community. He has published > 236 PubMed papers with recent focus on NGS conventional and breakthrough genome analysis (> 80 articles) and more recently in precision cancer medicine (31 articles). These publications have received more than 8420 citations with h-index: 72 (Scopus). He is reviewer in many high impact journals including some with impact factor (IF) >30, evaluator in innovative research projects (EU, France, Belgium, Luxemburg, Poland), and member in the editorial board of 25 international journals with IF. He has been invited speaker in many international and world congresses.
In HIV patients, alcohol consumption enhances pathological features of HIV infection by increasing viremia, suppressing immune responses, promoting non-adherence to treatment and causing poor HIV treatment outcomes. Liver disease is second the most common cause of mortality in HIV-infected patients. Progression tofibrosis is based on enhanced synthesis of extracellular matrix proteins accompanied with theirreduced degradation, and hepatic stellate cells (HSC) are the main source of extracellular matrix. Activation of HSC occurs via multiple mechanisms, and the important one is engulfment of apoptotic bodies (AB). Previously, we observed that in hepatocytes/hepatoma cells (designated as Hep), apoptosis is significantly increased by the combination of HIV and acetaldehyde (Ach). However, Hep is not the only source of apoptotic bodies (AB) in the liver, which also traps undergoing apoptosis HIV-activated lymphocytes (Ly). The goal of this study is to compare pro-fibrotic and pro-inflammatory changes in HSC after engulfment of AB from different sources, Hep and Ly. To mimic apoptotic effects of ethanol, AB from uninfected vs HIV-infected Hep and Ly were generated by exposure to UV light and then incubated with HSC. After 2 hr treatment with AB, we observed strong HIV-induced activation of pro-fibrotic markers (Col1A1, TGFβ, TIMP1mRNAs) by AB Hep, but not ABly. However, the induction of the inflammasome markers, NLRP3 and IL-1β will be the same. We conclude that there is cell-specific difference in ability of AB to activate the fibrosis by hepatic stellate cells, and apoptotic hepatocytes are the most effective fibrosis inducers.
Natalia Osna is Associate Professor at GI section, Internal Medicine Department, University of Nebraska Medical Center, where she has been since 2000. She is also Research Biologist at VA Medical Center. She received her MD/Ph.D. degree in 1984 at Riga’s Medical University, Riga, Latvia, where she worked as Senior and then Leading Scientist in the Department of Immunology before she moved to UNMC, Omaha, USA.
Hepatitis non-A, non-B ( hepatitis C) was recognized as a unique form of viral hepatitis in the late 1970s It took 2 decades for its full clinical characteristics, biochemical manifestations as well as its chronicity to be fully defined. Not until the introduction of interferon therapy in 1998-9 was any efficacy achieved. The development of direct acting antiviral agents utilized to inhibit viral replication therapeutic efficacy increased most recently to 95-100%. This success led to the projection that hepatitis C could be eliminated by 2020 with a reduction in cirrhosis and hepatocellular carcinoma thru 2030. Unfortunately, multiple obstacles prevent this favorable outcome and consist of the following: a lack of knowledge by physicians that the disease is a serious disease and importantly that it is treatable; the failure to identify asymptomatic patients and those with non-hepatic manifestations of the disease; the cost of drug therapy is prohibitive for individuals with no insurance and contributes to third party payers withholding therapy except for those with advanced disease; the failure to identify and treat individuals in the following groups: men having sex with men, incarcerated individuals, those that utilize drugs and participate in needle exchange and opioid replacement programs; those that are co-infected with HIV and hepatitis C; co- infected with hepatitis B and C; and those in long-term institutions for the mentally disabled and psychiatric patients.
Biography Dr. Van Thiel obtained his M.D. from the University of California Los Angeles and completed residency is in medicine at Cornell university hospitals and Boston University Hospital where he completed a fellowship in gastroenterology/hepatology at Boston University and the University of Pittsburgh. He has published more than 1100 papers in reputed journals and has served on the editorial boards of multiple journals in the fields of gastroenterology, hepatology, and liver transplantation.
Objective: chronic pelvic pain syndrome (CPPS) is a debilitating condition to a major impact on health-related quality of life, work productivity and health care utilization. The exact prevalence of chronic pelvic pain is unknown. Musculoskeletal dysfunction is frequently cited as a possible etiology.In other hand, recent neuroimaging studies have demonstrated a dysfunction in a specific region of the brain called motor cortex, in men with chronic pelvic pain syndrome (CPPS). The aim of this systematic review was to critically evaluate theeffect of physiotherapy on pain, physical activity and quality of lifein the treatment of CPPS patients.Chronic low pelvic pain has a variety of manifestations, including the most common causes of prostatitis. In most instances the malady is designated chronic prostatitis (CP) and empirical use of antibiotics represents the mainstay of therapy. However, virtually 95% of chronic prostatitis syndromes in men are nonbacterial and idiopathic, and represents a nonspecific pain disorder. Material and method: the present paper aims to systematically literature on the clinical intervention studies of chronic pelvic pain where physiotherapy was a sole or a significant component of the intervention. A systematic search strategy was established and executed in seven databases (PubMed, Google Scholar, Cochrane Clinical Trials, Science Direct, Pedro, Web of Science library and Medline). Various combinations of search terms related to chronic pelvic pain and its treatment were used.Duplicate or Non-English articles removed. One hundred and fifty papers full filled the inclusion criteria and were included in the review. Result: musculoskeletal dysfunction is the genesis of trigger points and histologically those in muscle present as small areas of myofibrositis characterized by the presence of a metachromatic substance with platelet aggregation and localized edema in the interfibrillar connective tissue.This disrupts pelvic floor muscle performance.These findings fit with the physical therapy approach to treating CPPS. Impairment in pelvic floor muscles is consistent with the observed dysfunction in a specific region of the motor cortex.Results demonstrated that functional connectivity between motor cortex and the posterior insula may be among the most important markers of altered brain function in men with CP/CPPS. Conclusion: according with the preliminary findings, we need to carefully establish the link between brain and pelvic floor muscle dysfunction before we can improve therapy for CPPS.
AfsanehNikjooy,is assistant professor of Physical Therapy, Department of Physical Therapy, at Iran University of Medical Sciences, Tehran, Iran. She is a member of the International Continence Society (I.C.S) and Iranian Continence society (Ir.C.S). She has worked in pelvic floor Physical Therapy for more than 14 years. She has managed several courses of pelvic floor Physical Therapy for master students in this field in Faculty of Rehabilitation, Iran University of Medical Sciences
TransAbdominal Sonography of the Stomach & Duodenum can reveal following diseases. Gastritis & Duodenitis. Acid Gastritis. An Ulcer, whether it is superficial, deep with risk of impending perforation, Perforated, Sealed perforation, Chronic Ulcer & Post-Healing fibrosis & stricture. Polyps & Diverticulum. Benign intra-mural tumours. Intra-mural haematoma. Duodenal outlet obstruction due to Annular Pancreas. Gastro-Duodenal Ascariasis. Pancreatic or Biliary Stents. Foreign Body. Necrotizing Gastro-Duodenitis. Tuberculosis. Lesions of Ampulla of Vater like prolapsed, benign & infiltrating mass lesions. Neoplastic lesion is usually a segment involvement, & shows irregularly thickened, hypoechoic & aperistaltic wall with loss of normal layering pattern. It is usually a solitary stricture & has eccentric irregular luminal narrowing. It shows loss of normal Gut Signature. Enlargement of the involved segment seen. Shouldering effect at the ends of stricture is most common feature. Enlarged lymphnodes around may be seen. Primary arising from wall itself & secondary are invasion from peri-Ampullary malignancy or distant metastasis. All these cases are compared & proved with gold standards like surgery & endoscopy. Some extra efforts taken during all routine or emergent ultrasonography examinations can be an effective non-invasive method to diagnose primarily hitherto unsuspected benign & malignant Gastro-Intestinal Tract lesions, so should be the investigation of choice.
Dr.Vikas Leelavati BalaSaheb Jadhav has completed PostGraduation in Radiology in 1994. He has a 23 Years of experience in the field of Gastro-Intestinal Tract Ultrasound & Diagnostic as well Therapeutic Interventional Sonography. He is the Pioneer of Gastro-Intestinal Tract Sonography, especially Gastro-Duodenal Sonography. He has delivered many Guest Lectures in Indian as well International Conferences in nearly 27 countries as an Invited Guest Faculty, since March 2000. He is a Consultant Radiologist & the Specialist in Conventional as well Unconventional Gastro-Intestinal Tract Ultrasound & Diagnostic as well Therapeutic Interventional Sonologist in Pune, India.
The aim of the study was to determine the efficiency of low-FODMAP diet in correction of small intestine bacterial overgrowth (SIBO) in adolescents with irritable bowel syndrome with diarrhea (IBS-D). Materials and methods. 80 adolescents suffering from IBS-D were examined. All patients were treated by using a monthly course of complex therapy, including spasmolytics, probiotics, enterosorbents. Children of group 1 were also received a low-FODMAP diet lasting up to 6 months. Patients of group 2 in addition to drug therapy during the entire period of treatment did not receive any special diet. Diagnosis of SIBO was based on a non-invasive hydrogen breath test with a load of lactulose using the analyzer of exhaled hydrogen "LactofaH2" ("AMA", Russia) before the therapy, 1 and 6 months after the start of the treatment. Results. SIBO was diagnosed in 43 (71.7 %) children with IBS-D: in 22 (73.3 %) patients of group 1 and in 21 (70.0 %) children of group 2. A month after the start therapy SIBO was determined in 8 (26.7 %) patients of group 1 and in 14 (46.7%) children of group 2 (p <0.05). Six months after the initiation of treatment, against the background of diet therapy, SIBO was diagnosed in 9 (30.0 %) patients of group 1 and in 18 (60.0 %) children of group 2. The level of significance of differences between groups – p<0.05. Conclusion. Thus, the using of low-FODMAP diet in adolescents with IBS-D may reduce the incidence of SIBO
Andrew Nalyotov has completed his PhD from Donetsk National Medical University named after M. Gorky, Ukraine. At the present time works at the Department of Pediatrics and Childhood Infections of Donetsk National Medical University named after M. Gorky, that based on City Children's Clinical Hospital № 1 in Donetsk.
Chronic Hepatic deficiency due to the ingestion of alcohol remains as one of the main causes of morbidity and mortality in our country. From it a variety of complications arise, one of them is the Hepatopulmonary Syndrome, which usually goes unnoticed and undiagnosed; this syndrome is distinguished by the presence of hypoxemia and pulmonary vasodilation. The gold standard to establish a diagnostic is contrasted Echocardiogram. No pathognomonic sign is known for this syndrome, which leads the present elaboration to evaluate the use of orthodeoxia by pulse oximetry as a screening test in the detection of Hepatopulmonary Syndrome cases. The clinical picture of the Hepatopulmonary Syndrome is insidious and is not counted as a pathological sign, which causes a low index of suspicion and belated diagnostics. This is why there´s so much determination to the orthodeoxia as a proposed index for the opportune detection of Hepatopulmonary Syndrome to be later corroborated with more extensive studies. Platypnea and orthodeoxia defined as dyspnea and deterioration in the arterial oxygenation respectively included by orthostatism are extremely common in this syndrome and present themselves in up to a 70% of the patients, primarily orthodeoxia suggests the diagnose.Although it was a very short study with a small amount of patients, the purpose was to establish orthodeoxia as a screening test for the detection of Hepatopulmonary Syndrome
Physician Assigned to the service of Internal Medicine and Intensive Therapy. Mexican Institute of Social Security, Institute of Health of the State of Mexico.Master of teaching Professor of Undergraduate School of Medicine UniversityAutonomyof State of Mexico. Author of several articles of Latin American magazines
The incidence of gastroesophageal reflux disease in the population of industrialized countries is high and ranges from 20 to 40% in the age groups between 45-64 years, with a further increase in the incidence in the age between 64-74 years. The natural history of the disease requires continuous recrudescence alternated with quiescent phases. In view of these epidemiological data, the importance of the social problem and the high health costs is cleared. It follows the interest of pharmaceutical companies, the companies of electromedical and producing toolkits endoscopic and surgical companies. Objective: In this session, I intend, with the participation of colleagues internists and surgeons, to make a brief stock of the situation, about the gastro-esophageal reflux disease. I will make a tour of the clinical presentation, the increase of incidence, especially of so-called atypical forms and symptoms of gastro-pharingeal reflux (high reflux), emphasizing how many patients are refractory to therapy. Patients who benefit from medical treatment, they become dependent on care. Whereas, many are young and that medical therapy has adverse side effects, such as anemia, osteoporosis, and infections, is the need for alternative therapies. Physiotherapy global posture, for example, can be a transient and partial support. The ultimate solution is or should be surgical. Considerations: Surgical therapy makes use of minimally invasive or laparoscopic method, which shortens the hospital stay. But an endoscopic surgery, easy, repeatable, free from postoperative complications, can be performed in day surgery, would be ideal for this type of chronic disease. In reviewing the different techniques, that have been proposed over the last 20 years, I relate the considerations, derived from the international literature. This presentation is concluded by presenting a last device, manufactured in Germany, derived from its precursor, the NDO Plicator, which is making use of the addition of heads polytetrafluoroethylene (PTFE), which retain the suture threads from the traction, exerted by the tissues, seem to improve the seal in time. Conclusions: I carry scientific studies that have compared the operations, performed with GERD-X Plicator, to surgical interventions of fundoplication, with satisfactory results. My invitation is to continue to seek solutions with endoscopic surgery, which is the most appropriate technique for this type of pathology.
Antonio Iannetti has done his degree in Medicine and Surgery and Specialties in "Gastroenterology" and "Internal Medicine" at the University of Rome. 1980-1983 University of Los Angeles (USA), he is interested endoscopic sclerosis of esophageal varices and retrograde cholangiopancreatography-endoscopically. He is University Professor and Chair of Gastroenterology - University of Rome. He is head of the Digestive Endoscopy Service of the University Hospital Umberto I in Rome. He is an expert of the Ministry of Health for Gastroenterology
Statement of the Problem: Liver fibrosis is the common end stage for most chronic liver injuries which leads to irreversible cirrhosis with the risk of liver failure and hepatocellular carcinoma. Sitagliptin, a Dipeptidyl peptidase 4 inhibitor (DPP4-I), has been developed as a new possible treatment for type-2 diabetes mellitus. It has been suggested that DPP4 is involved in the development of several liver diseases, such as chronic hepatitis C (CHC) and hepatocellular carcinoma (HCC). Other reports showed that DPP4 is expressed on the surface of reactive fibroblasts including activated HSCs. Therefore, this study was designed to assess the antifibrotic, antioxidant, and anti-inflammatory effects of sitagliptin against liver fibrosis induced by CCl4 in rats and to foresee an unusual clinical application of sitagliptin. Methodology &results: the antifibrotic effect of sitagliptin was assessed using CCl4-induced experimental liver fibrosis model. Rats received CCl4three times a week for 7 weeks, as well as daily oral treatmentsof Sitagliptin (100 mg/kg) during the 7 weeks of intoxication. Hepaticfibrotic changes were estimated by measuring hepatic enzymes, markers of liver fibrosis, oxidative stress, and inflammation as well as marker of HSCs activation.It was found that sitagliptin ameliorates liver fibrosis, mainly via inhibiting the fibrogenesis and proliferation of activated HSCs response via inhibiting the release of TGFβ1, attenuating the activation of hepatic stellate cells via reduction of α-SMA expression in liver, inhibition of hepatic oxidative stress and augmentation of anti-oxidant defenses, and inhibition of proinflammatory cytokines as IL-6. Conclusion & Significance: this study showed that sitagliptin attenuates the progression of liver fibrosis induced by carbon tetrachloride in rats. Looking forward clinical application, this study may introduce a new therapy for treating liver fibrosis in humans especially for diabetic patients suffering from liver diseases.
Mai El-Sayed Ghoneim has graduated from faculty of pharmacy Alexandria University, Egypt. She is now researcher at the faculty of pharmacy Tanta University, Egypt. She works as a pharmacist at Liver research institute in Egypt. She has published one paper on biomedicine and pharmacotherapy journal. She also has served as a Reviewer on Oncotarget journal, AJPCR and molecular medicine reports. She is speaker at World Congress on Gastroenterology conference, Dubai, 2017.