4^th International Conference and Exhibition on Pathology July 13-15, 2015 New Orleans, USA

Biography:

K. H. Ramesh did his PhD, in Human Cancer Cytogenetics from Bangalore University, India. He trained under the guidance of world renowned geneticist Avery Sandberg, MD., at Roswell Park Cancer Institute, Buffalo, USA. He is Board Certified in Clinical Cytogenetics; currently a Diplomate of the American Board of Medical Genetics and Genomics, and Fellow of the American College of Medical Genetics and Genomics. At present he is the Director of Cancer CytoGenomics and Associate Professor of Pathology at Montefiore Medical Center and Albert Einstein College of Medicine, Bronx, USA. He has over 25 years of experience in Human Cancer Genetics

Abstract:

Breast cancer is the most common malignancy in women of all ethnicities. Standard treatment involves surgical resection; pathologic analyses that includes morphologic, immunohistochemistry (IHC) and Fluorescence In Situ Hybridization (FISH) analysis to determine ER, PR, and HER2 parameters in the tumor. The HER2 gene (17q11.2-12) is amplified in 20% of invasive breast cancers. Patients with tumor positive-HER2 gene amplification are eligible for adjuvant chemotherapy with Trastuzumab (Herceptin), resulting in longer survival. Studies have shown that 40% of breast tumors show genetic heterogeneity (GH) as per ASCO/CAP (2013) criteria. Breast tumors with an IHC score of 2+ qualify for FISH testing to rule out HER2 gene amplification, and if positive, patients are eligible for Herceptin treatment. GH is defined as the presence of >5% and <50% of 20 tumor cells showing HER2- amplification. The 40% of breast tumors that show GH pose an unresolved dilemma in treatment. Our aim is to establish the clinical significance of HER2 GH in breast cancer. Data is correlated with patient demographics, histological tumor type and stage, IHC scores, treatment regimen and morbidity to determine if GH has an impact on treatment modality. These outcomes include differences in survival (Kaplan-Meyer survival curves) and morbidity from the treatment (cardiomyopathy). Our hope is to determine whether a systematic study of outcomes among patients with HER2 GH with or without equivocal FISH results will address reconsiderations of treatment guidelines for these patients.

Biography:

Maria Teresa Mascellino has completed her MD at the age of 25 years from University "La Sapienza" of Rome and specialization studies in Clinical Microbiology and Infectious Diseases from University "La Sapienza" of Rome. She is Director of Microbiology Laboratory in the Department of Infectious Diseases. She has published more than 80 papers in reputed journals and has been serving as an editorial board member of repute. She is member of many scientific societies and has participated in relevant International Research Projects.

Abstract:

Klebsiella pneumoniae carbapenemase (KPC)-producing are associated with increased mortality due to the resistance to the most antibacterial agents. Pan-drug resistant (PDR) K. pneumoniae infections have been recognized as an emerging challenge worldwide, due to the lack of therapeutic options . Strains of third-generation-cephalosporin-resistant and carbapenem-resistant K. pneumoniae are rapidly spreading. Preliminary data suggest a role of unconventional antibiotic combinations against colistin-resistant carbapenemase-producing isolates (CP-Kp). Aim of our work was to study the infections due to carbapenemase-producing Kl. pneumoniae , associated with a high mortality rate, belonging to patients hospitalized in a tertiary care setting. In these cases the therapeutic options are limited especially when associated with colistin resistance. In this case , a double carbapenem regimen has been shown to be effective and safe. Herein, we evaluated through antibiotic kill studies the in vitro synergistic activity of meropenem plus ertapenem against MDR Kl. pneumoniae isolated from 3 patients with bacteraemia who were successfully treated with double-carbapenem therapy. The results of time killing analysis showed that ertapenem or meropenem alone exhibited an initial reduction in log CFU/mL followed by a significant regrowth at 24h in all the patients. When the double-carbapenem combination was assessed, a bactericidal and synergistic activity was achieved at 4, 6, 8 h and maintained at 24 h at concentrations of meropenem 0.5xMIC plus ertapenem 1xMIC, meropenem 1xMIC plus ertapenem 1xMIC and meropenem 2xMIC plus ertapenem 1xMIC in all the patients. In our patients, ertapenem plus meropenem induced clinical (defervescence in 48 h) and microbiological (absence of growth in blood cultures performed 48 h after therapy) responses. In the in vitro studies, combination treatment exhibited a higher bacterial killing than monotherapy, even in the presence of high carbapenem MICs. In all the isolates, the combination treatment maintained bactericidal effect up to 24h, thus confirming the clinical efficacy of this innovative regimen. In summary, this report suggests that meropenem plus ertapenem might be considered a promising option in CP-Kp infections, especially in patients for whom colistin treatment is inappropriate due to resistance or toxicity.

Biography:

Kim Solez, M.D., FRCPC, Professor of Pathology at the University of Alberta, and President and CEO of Transpath Inc., is one of the world’s foremost kidney pathologists. He is the father of the Banff classification that sets standards worldwide for how biopsies from kidney and other solid organ transplants are interpreted, and started the post-earthquake disaster relief task force of the International Society of Nephrology. He is a popular blogger on internetevolution.com, and directs NKF cyberNephrology, a joint venture of the National Kidney Foundation (U.S.) and the University of Alberta. Kim has also created many educational videos for the Lifeboat Foundation

Abstract:

There have been many articles about mentoring but most deal with short-term effects and assume few mentors per person, and that mentoring is in the past and unidirectional. We present the forty-year mentoring influence of one physician researcher/kidney pathologist, Liliane Striker (1937-2004), on the career of another, Kim Solez. The application of the technological singularity to medicine, development of the Technology and Future of Medicine course, and expansion of Virchow’s Medicine Writ Large idea in Dr. Solez’s career can all be traced back to 1974 conversations between Drs. Striker and Solez. Now through Dr. Solez’s students one can imagine the influence of those 1974 ideas propagating for a hundred years or longer. Mentoring/influencing effects are active, ongoing, and in the present. The process involves not just conventional mentoring, but also reverse, collaborative, and natural mentoring. Dunbar’sNumber, a concept previously used to describe the 150 meaningful relationships possible for human beings (range 100-200) based on cognitive limits and neocortex size, here fits the number of mentors/influencers in one lifetime in memory at one time. The large number of influencers here is related to the requirements of consensus generation worldwide leading the Banff classification process over the past twenty-three years. Further investigation will determine if 150 mentors/influencers per person applies only in this case or is a human limit that can be generalized. The present paper may stimulate others to generate mentor/influencer lists that can bring new insights to the history of ideas and individuals in medicine and science generally.

Biography:

Dongfeng Tan received initial pathology training in China and Germany. After pathology residency at Yale University Medical Center (1994 to 1998), he completed an oncologic surgical pathology fellowship at Memorial Sloan-Kettering Cancer Center in New York. He joined Roswell Park Cancer Institute as an Assistant Professor of pathology in 1999. In 2004, He became an Associate Professor of Pathology at The University of Texas (UT) Health Science Center at Houston. He joined the faculty of The University of Texas MD Anderson Cancer Center in 2006 and was promoted to Professor in 2010. Currently, he is Professor of pathology and laboratory medicine, and medical oncology at MD Anderson Cancer Center. He has conducted independent and collaborative clinical and translational investigations and has been a principal investigator (PI) and Co-PI of funded research programs. These academic activities have led to 130 articles published.

Abstract:

Presentation of advancements in precision medicine, outcome management and genetic classification require high-quality biospecimens. Some highlights of the presentation: • Keep precious biological samples, including tissue and serum, safe and secure in our state of the art, CAP accredited and ISO certified facility • Locate samples quickly and easily through our easy to access sample reporting and retrieval systems • Improve research efficiency with comprehensive logistics management including collection, sample characterization, transportation, cryopreservation and storage • Virtual biobanking

Biography:

Jaulang Hwang received his Ph.D. in Biological Chemistry from the University of Michigan, Ann Arbor. Dr. Hwang was supervised by Dr. Ira Pastan, NCI, NIH, for his post doctorate training. He then returned to Taiwan and as an Associate Research Fellow and was later promoted to Research Fellow, at the Institute of Molecular Biology, Academia Sinica. In addition to his research at Academia Sinica, Dr. Hwang held many roles including: President of Taiwan Genomics and Genetics Society, Associate-Director of the Institute of Molecular Biology, Academia Sinica, and Dean of the College of Sciences, National Chung Cheng University. Currently, he is a Distinguished Professor at the Department of Biochemistry, Molecular and Cellular Biology, Taipei Medical University.

Abstract:

Elevated expression of tumor-associated carbohydrate antigens (TACAs) is associated with various cancers. A variety of malignant and normal tissues have been screened by immunochemistry using antibodies against TACAs. Overexpression of TATAs (tumor-associated carbohydrate antigens) has been observed on the cell surface of many malignant tumors. The Tn antigen (GalNAc-Ser/Thr) is one member of TACAs presented as mucin-type carbohydrates. Using the LAE vaccine technology (Linear Array Epitope), we have developed an anti-Tn vaccine, which induces anti-Tn antibodies with high specificity and high affinity in mice. Using the anti-Tn antibody, we have demonstrated that the expression of Tn is positively correlated with the degree of malignancy in prostate, breast, colon, cervical,oral squamous cell carcinoma (OSCC), and pancreas cancers. In the case of OSCC, the expression of Tn was positively correlated with staging recurrence, and distant metastasis as well as withinvasive pattern grading score (IPGS). The results suggest that Tn expression may serve as a reliable indicator for OSCC prognosis evaluation. Our studies have also demonstrated that anti-Tn vaccine can protect against spontaneous prostate cancer formation in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice. Together, our results show that tumor-associated carbohydrate antigen, Tn, can serve as a cancer prognosis marker and therapeutic target.

Biography:

Kazuaki Nakane obtained his PhD at Kanazawa University. He solved ‘peeling phenomena (a vibration occurs when a thin tape is peeled off)’ mathematically. His research includes: (i) Non-linear partial differential equations, (ii) Numerical Computations. From 2008, he propose a new numerical method to analyze the structures which has no patterns by using a homology concept. He received ‘The visionary research’ from ‘Takeda Science Foundation’ as well as several other Japanese awards. He was the researcher of the project supported by the ‘Minister of Economy, Trade and Industry, Japan’ in Osaka University. Now, he is developing aquantitative evaluation methods for the structures (tissue) from images in Osaka University. His method can be applied many structures, for example fracture surfaces, silica gels, grains in the quenching steels and the morphological change of microglia. He was invited for international conferences of many fields.

Abstract:

Pathological diagnosis provide important information in determining the treatment policy. Except for the developed countries, the number of pathologists is not sufficient. In such countries, they are often in large hospitals of metropolitan areas, namely, pathologists are unevenly distributed. Sufficient service to patients cannot be offered in this situation. Development of remote diagnosis and automatic diagnostic system using a network are desired. The development of digital pathological diagnosis systems have been constructed by the algorithm based on the pattern recognition technique. However, the morphology of the cancer tissue are quite complex, it is very difficult to make effective systems. A region of interest (ROI) is a part of tissue that contains important information for diagnosis. Since malignant tumors grow in the innermost layer, most ROIs will be located in the colonic mucosa and will be an accumulation of tumor cells and/ or integrated cells with distorted architecture. An area with unusual contact degree is expected to be a potential ROI. Recently, a new image analyzing method by using a homology concept for pathological digital images has been developed. Homology is a mathematical concept that can quantify the contact degree. Calculating the homology value in a unit area of the pathological image, we can determine whether the ROI by this method. To get the homology values, we need to convert the pathological images to the binarized one which can be considered the mathematical object. The binarized thresholds are determined by the RGB (red green blue) information. Although we have many false positives and there is a possibility of missing undifferentiated types of cancer, this system is very effective for detecting ROIs. Because our method can detect ROIs very quickly, it could be used to screen WSIs.

Biography:

Praveen Gurpur was trained as a medical doctor in India. He then went on to do his PhD at the University of Illinois at Urbana-Champaign. For his PhD, he worked on a novel integrin based therapy for muscular dystrophy, using small molecules. Following his graduation, he did his post-doctoral training at the University of Nevada School of Medicine, where he developed a cell-based screening platform using muscle stem cells to identify small molecules against muscular dystrophy. Dr. Gurpur then worked in a drug discovery company in India where he managed the in vitro assay development program for pain and inflammation. He then joined Siemens, India, where he is a project manager in Biosciences. Dr. Gurpur has several publications to his credit. He has also been an acclaimed teacher for an undergraduate course. Dr. Gurpur’s expertise spans across Clinical Medicine, Molecular & Cellular Biology, Drug Discovery and Medical Devices, among others.

Abstract:

One of the key healthcare delivery problems in developing countries is the non-availability of qualified pathologists in resource poor settings such as rural areas. Patients have to spend significant time, money and effort in traveling to urban areas for accessing medical diagnosis/care. It is highly desirable to have a system that enables local, minimally trained health workers to transmit microscopic images of patient samples such as cytology smears for examination by a remote pathologist. The remote pathologist can access images, analyze them and give their opinion. Based on the opinion, the healthcare worker advises the patient to go to the urban clinic only if is necessary. We have developed a telemicroscopy device for capturing images from a slide into a mobile device. This device was tested in a cohort of patients in and around Bangalore, India for oral cancer detection using brush biopsy. Incision/punch biopsies of the same patients were considered the gold-standard against which results from the telemicroscopy device were tested. The talk will focus on results of the study and potential of the device for oral cancer screening.

Biography:

Dr. Maison Abu Raya is motivated young doctor has completed her MD (cum laude ) and graduated at the age 0f 26 from the Technion Institute of Technology, Rappaport Faculty of medicine, Haifa, Israel. One of the prestigious medicine schools in Israel. Currently, Dr. Maison is a chief resident in internal medicine in Carmel medical center in Haifa.

Abstract:

Histomorphometry is a quantitative method for investigating changes in shape, size and orientation of cells in tissues. The aim of our study is to use computerized morophometry in order to quantify the histological changes that occur in liver biopsies obtained from patients with chronic HCV, and to predict the response to medical treatment in these patients. Patients with chronic HCV genotype 1, with Metavir score F1 and F2 followed at our liver were selected and grouped according to treatment response {SVR and non-SVR}. Histological slides from the pretreated liver biopsies were scanned using the dot slide virtual microscopy Olympus system. The ImagePro plus 7.0 program has been used to quantify the amount of collagen fibers, the number of inflammatory cells and textural changes of the livers parenchyma. The Matlab software was used to calculate fractal and lacunar dimensions of the liver parenchyma in order to capture any structural changes in the livers general architecture. Our study has shown that morphometric variables including the density of collagen fibers, the fraction of inflammatory cells per portal space area, and textural parameters were found to be statistically significant and could be combined together in a mathematical formula, in order to predict response to treatment in HCV patients, with sensitivity of 93%, and 100% specificity. In conclusion morphomertic method is promising and may contribute to developing a novel expert guided automatic system predicting response to treatment in chronic HCV patients, and may be used in the future to investigate liver diseases due to different etiologies.

Biography:

Masahiko Abematsu has completed his Ph.D at the age of 32 years from Kagoshima University and postdoctoral studies from Nara Institute of Science and Technology. He is the clinical lecturer of Orthopaedic Surgery, Kagoshima University Medical and Dental Hospital. He has published more than 20 papers in reputed journals and serving as an reviewer member of ‘Journal of Neuroscience Research’, ‘Cellular and Molecular Neurobiology’, ‘Journal of Dermatological Science’ .

Abstract:

Neural stem cells (NSCs) possess the ability to self-renew and to differentiate into the three major cell types found in the central nervous system (CNS). Recent studies have shown that epigenetic gene regulation events such as DNA methylation and histone modification play important roles in regulating NSC fate specification. In this presentation, we have previously shown that the histone deacetylase inhibitor valproic acid (VPA) enhances neuronal differentiation of NSCs. Perhaps because these patterns of NSC differentiation are exquisitely controlled during normal embryonic development, restoration of damaged neural networks in the injured adult CNS is severely limited. Here, using a mouse model of spinal cord injury (SCI), we show that transplanting NSCs and administering VPA enhances the functional recovery of their hindlimbs. Neuronal differentiation of transplanted NSCs was promoted in VPA-treated mice. Anterograde corticospinal tract tracing revealed that transplant-derived neurons partially reconstructed the broken neuronal circuits, most likely in a ‘relay’ manner. Ablation of the transplanted cells abolished the recovery of hindlimb motor function, indicating that transplanted cells contributed directly to the improvement of motor function. These data raise the possibility that epigenetic regulation in transplanted neural stem cells can be exploited to provide treatment for SCI.

Biography:

Nuray Bassüllü is a Medicine Doctor (PhD-medicine). She is an Associate Professor Pathology Department, Istanbul, Turkey. She had completed her PhD from Istanbul University, Cerrahpasa Medical Faculty, Department of Pathology and Post doctoral studies from Ä°nonu Universty and Istanbul Bilim University Medical Faculty Department of Pathology in Turkey. She had published more than 30 papers in reputed journals and serving as an Editorial Board Member of repute. Her research interest is on the Hepatocellular carcinoma and hematopathology.

Abstract:

Background & Objective: It was aimed to investigate the expressions of c-erb-B2, EGFR, PTEN, mTOR, PI3K, p27 and ERCC1 in Hepatocellular carcinomas (HCC) and their correlations with other clinic pathologic features. Methods: Immunohistochemistry was performed by these markers in 50 HCC cases. Statistical analysis was done to examine the relationships of them with clinic pathologic characteristics and survivals. Results: c-erb-B2 staining was seen only cytoplasmic in 92%, membranous EGFR in 40%, PI3K in all, mTOR in 30%, reduced or absent PTEN in 56%, loss of p27 in 92% of the cases. c-erb-B2, mTOR, p27 were correlated with multiple tumors, p27, mTOR and EGFR were with AFP levels, EGFR and ERCC1 with angiolymphatic invasion, EGFR with histological grade. Survivals showed significant difference between therapy modalities, AFP levels, angiolymphatic or lymph node invasions, ERCC1 and p27 expressions. Conclusions: It was shown that c-erb-B2; EGFR, mTOR, ERCC1 and p27 may play role in hepatocarcinogenesis and may be significant predictors of aggressive tumor behavior.

Biography:

Trupti Shetty has completed her graduation from RGUHS, Bangalore and Post-graduation Pathology from Yenepoya University, Mangalore. She is currently working as Assistant Professor in the Department of Pathology, MGM Medical College, Navi Mumbai. She has presented a poster at National level and has published many papers in reputed indexed journals both at national and international levels.

Abstract:

The Gold nanoparticles (AuNP’s) attract enormous scientific interests due to their biomedical applications in chemical sensing, biological imaging, drug delivery and cancer treatment. However their toxicity due to nano size and pattern of bioaccumulation is rarely discussed. This study aims to address the effects of size dependent and duration of exposure of AuNP’s on major organs with respect to male sex in zebra fish as an upcoming model for toxicity based studies. The study was designed to evaluate chronic exposure of AuNP’s with average diameter of 15 and 45 nm. A total of 36 healthy adult male zebra fish of the same age and weight were maintained. Fishes were randomly divided into three groups: Two test groups of size dependent AuNP preparations (12 fishes per group) and one control. A concentration of 20 μg/gm of AuNP’s was orally administered once for 28 days. Histopathological features on major organs were evaluated for signs of toxicity and the patterns of bioaccumulation of gold content in major organs were assessed using ICP technique. In comparison with control group, chronic exposure to AuNP’s of both size range showed variations in hepatic, renal parameters and size dependent alteration in the basal architecture of the brain as well as testicular tissues with no significant effects on myocardium. The AuNP’s possess quantum effect on size and duration of exposure. The histopathological changes suggest that AuNP’s of 15 nm as compared to 45 nm on repeat administrations interact with cellular proteins in a widespread manner causing alterations of major organs.

Biography:

Gerard Lozanski completed his graduate medical education at Karol Marcinkowski Medical Academy in Poznan, Poland in 1987. He finished his residency in Pathology at Summa Health System in Akron and fellowship in hematopathology at Cleveland Clinic in Cleveland OH. Dr. Lozanski joined Ohio State University as faculty in 2002, and is currently Associate Professor of hematopathology, director of hematopathology division, medical director of clinical flow cytometry laboratory and medical director of hematopathology fellowship program. His research interest focuses on low grade lymphoproliferative disorders with an emphasis on CLL, Follicular Lymphoma and Minimal Residual Disease detection by flow cytometry.

Abstract:

Chronic lymphocytic leukemia (CLL) is the most common B cell lymphoid malignancy in the western world. Leukemic cells are characterized by autonomous activation of B cell receptor (BCR) pathway and variable genetic and molecular lesions that are reflected by a highly varied clinical course. Some patients may never require therapy while others must be treated with chemo-immunotherapy to survive. Of treated patients, a large subset will relapse with disease that becomes resistant to all available classical therapies. Recently approved BCR pathway inhibition by irreversible inhibitor of Burton Tyrosine Kinase (BTK), Ibrutinib, affords effective treatment of these patients. Continuous therapy with Ibrutinib results in durable remission with marked reduction of tumor burden and improvement of disease symptoms. Unfortunately, a small subset of Ibrutinib treated patients will develop resistance to Ibrutinib that is mediated by mutation in drug binding site of BTK gene and/or activating mutation of PLC-gamma gene. CLL with fully developed acquired resistance to Ibrutinib is characterized by an aggressive clinical course that limits effective intervention in these patients. Sensitive and accurate early detection of these mutations at low allelic burden allows preemptive alteration in therapy in these patients. The ideal test should afford very deep coverage of BTK and PLCg genes with high sensitivity even is samples with low number of leukemic cells. This presentation will describe our experience of development and validation of Ion Torrent based BTK and PLCg mutation detection assay that we currently use in CLIA certified molecular laboratory for CLL patients treated with Ibrutinib.

Biography:

James Michaelson is the Director of the Laboratory of Quantitative Medicine, Member of the Departments of Pathology and Surgery at the Massachusetts General Hospital and Associate Professor in Harvard University. His research concerns: The assembly of very large databases on patients; the development of improved mathematical methods for predicting cancer outcome; the analysis of patient outcome and cost; the analysis of cancer screening; the mathematics of growth; the mathematics of metastasis; the use of modern computer speech and telephony to design systems that improve patient compliance and the development of advanced method for imaging cancer specimens.

Abstract:

Growth is the most essential quality of multicellular organization. The creation of animal life, that is, the creation of the integrated biological entity that is the aggregate result of the mitotic offspring of a single founder cell, often initiated by fertilization, was made possible by the limitation of cell division to a fraction of cells, g, such that g≈1 at fertilization, declining towards zero as adult size is reached. In precisely what form this decline occurs, and how animals achieve such growth, have been unanswered questions for more than a century. In order to examine the role of cell division in growth, we assembled data on the number of cells in the organism, N, by age, t, in days from fertilization until adulthood, for 11 organisms - humans, frogs, nematodes, chickens, cows, geese, mice, quail, rats, turkeys, and clams - and calculated the value of the growth fraction, g as size, N, increases. These measurements revealed that the rate of growth starts out as exponential, and then the growth fraction transitions to a rapid decline, which is well captured by the expression g=A^N^B, where parameters A and B characterize each organism. We also identified a possible mechanism by which the molecules that control cell division can lead to such growth, as the unobvious consequence of the discrete nature of such molecules. These findings suggests a general growth law for capturing the large-scale feature of growth from the fertilized egg to adulthood, where the rate of growth= [ln(2)/C]*N*A^N^B, where C is the cell cycle time. This new method for charactering growth, and the new growth equation found by this method, have a variety of practical applications, from developing methods for optimization of the harvesting of clams, to assessing the growth of human fetuses and children, to understanding the growth of cancer, and to creating improved computer simulations models for determining the optimal ways to use cancer screening to lower the cancer death rate.

Biography:

Cynthia D Guy completed her MD degree from the Medical University of South Carolina in Charleston, SC in 1993 and completed her AP/CP training at Emory University in Atlanta, GA 1998. She then completed a Cytopathology Fellowship at Duke University in Durham, NC in 1999. She is currently an Associate Professor and the Chief of the Liver and GI Pathology Section in the Department of Pathology at Duke University. She has published more than 75 peer-reviewed manuscripts. She enjoys a busy clinical practice and participation in translational research.

Abstract:

Introduction: The global “obesity epidemic” has thrust nonalcoholic steatohepatitis (NASH) and the metabolic syndrometo the forefront of health-related concerns, and both are linked to the rising incidence of hepatocellular carcinoma (HCC). Successful treatments are lacking. Deeper insights into the cellular signaling mechanisms driving these processes are needed and may shed light on possible therapeutic targets.
Body: The Hh signaling pathway was first discovered in 1980 as an embryonic morphogen regulating Drosophila segmentation patterning. Over the past decade, however, the importance of Hh signaling in human liver disease has beenrecognized. Hh pathway activity has beenidentified in adult and pediatric NASH and HCC. For example, Hh signaling has been linked to NASH ballooning; Hh ligands are released from ballooned hepatocytes and act as damage associated molecular pattern molecules (DAMPs) to drive myofibroblastic fibrogenesis. The Hh pathway has been linked to the ductular reaction and fibrosis progression in adult NASH. Furthermore, Hh pathway signaling was recently shown to be downregulated in NASH following successful Vitamin E therapy. Finally, Hh signaling has also been linked to hepatocellular carcinogenesis via the Warburg effect. Tumor cells release Hh ligands which act in a paracrine manner to drive the production of lactate in neighboring stellate cells. The stellate cell lactate is then used by tumor cells to fuel aerobic glycolytic activity and ATP production.
Conclusions: Recent advances in our understanding of the importance of Hh signaling in NASH and HCC may provide insights into potential therapeutic targets for these emerging worldwide diseases.

Biography:

Aysegul Sahin is an internationally recognized breast pathology expert who is a faculty member at MD Anderson Cancer Center since 1988. She received her medical doctor degree from University of Ankara in 1980, completed Anatomic and Clinical Pathology Residency at Oregon Health Science University, and did Surgical and Oncologic Surgical Pathology Fellowships at the University of Iowa Hospital and Clinics and the UT M. D. Anderson Cancer Center. Currently, she is the Section Head of Breast Pathology and Director of Education in the Department of Pathology and Breast Pathology Fellowship Program. She is also the Director of the Breast Tumor Bank. Dr. Sahin is actively involved with clinical and translation research programs related to breast cancer. She has published over 310 peer-reviewed manuscripts on breast pathology especially on morphologic features of invasive and in-situ carcinomas, and high-risk lesions biomarkers of breast cancer progression, prognostic and predictive marker evaluations in breast cancer. Dr. Sahin has also published multiple book chapters on pathology of breast lesions. She is an executive committee member of International Society of Breast Pathology and member of national and international pathology societies.

Abstract:

Neoadjuvant chemotherapy refers to chemotherapy administered before surgery and it is the standard treatment in locally advanced breast cancer. In the last decade the indications for neoadjuvant chemotherapy has broadened to include its use in the treatment of earlier stages of breast cancer with the aim to obtain tumorshrinkage and improve the rate of breast-conservingsurgery.More recently, this treatment modality is increasingly used to obtain a quantifiable evaluationof sensitivity or resistance to chemotherapy. The potential of tumor response might also allow individualization of systemic treatments and therapid assessment of new drugs. Furthermore, clinical trials in neoadjuvant setting are increasingly being utilized for the evaluation of new drugs and novel therapeutic strategies using pathological complete response, a surrogate marker for survival, as the primary endpoint. Complete eradication of invasive tumor cells in the primary tumor bed following neoadjuvant therapy is strongly correlated with improved disease-free survival and overall survival. The excision or mastectomy specimens display a range of histopathologic changes after neoadjuvant chemotherapy. Appropriate specimen handling is essential to evaluate response to neoadjuvant chemotherapy and includes not only careful assessment of specimens but also requires correlation with clinical and imaging findings. There are different methods to quantitate residual tumor. In this presentation I would like to review methods to evaluate breast resection specimens after neoadjuvant chemotherapy, discuss the classifications systems of residual tumor burden, and tumor biomarkers related to response to neoadjuvant chemotherapy.

Biography:

Jiong Yan is an Assistant Professor in the Department of Pathology and Laboratory Medicine at University of Saskatchewan. She obtained her doctoral degree in Medicine in China and her PhD degree in molecular Genetics at Baylor College of Medicine. She then completed her Pathology residency and Hematopathology fellowship trainings at New York-Presbyterian Hospital/Weill Cornell Medical Center. She has published about 20 peer-reviewed papers in reputed journals.

Abstract:

Diffuse large B cell lymphoma (DLBCL) is the most common aggressive lymphoma, accounting for 30-40% of the non- Hodgkin lymphoma. DLBCL has been demonstrated to be biologically heterogeneous. Gene expression profiling has identified two main subgroups of DLBCL, germinal center B cell like (GCB-like) and activated B cell like (ABC-like) DLBCL. Current standard therapy includes cyclophosphamide, doxorubicin/epirubicin, vincristine, prednisone and rituximab (R-CHOP). With this regime, ABC-like DLBCL has significantly inferior outcome compared with the GCB subtype. The advance in technology has enabled identification of several unique molecular pathways in different subtypes of DLBCL. Mutations in EZH2, a gene encoding a histone methyltransferase, have been identified only in GCB DLBCL. Mutations in genes involved in B-cell receptor/NF-κB pathway have been predominantly found in the ABC DLBCL. The findings have resulted in the development of novel agents targeting different molecular pathways. These novel agents are promising in improving patient outcomes. This talk will review different molecular pathways identified in the ABC and GCB subtypes as well as novel therapeutic agents under development.

Biography:

Andrea Rodrigues Cordovil Pires was associated professor for 18 years at the Pathology Department of the School of Medicine from Universidade Federal Fluminense, Brazil. She is medical director of Fonte Medicina Diagnostica, a reference anatomic and molecular pathology laboratory. She has published more than 20 papers in reputed journals, with emphasis in Hematopathology and immunohistochemistry.

Abstract:

EBV positive diffuse Large B-cell lymphomas (DLBCL) are clonal proliferation of EBV+ B-cells occurring in patients who have no prior history of immunodeficiency or lymphoma. Its prevalence is 8-11% among DLBCL in Japan and Mexico and less than 5% in western countries, incidence increasing with aging. A tissue microarray (TMA) with 80 cases of DLBCLs, was submitted to EBV in situ hybridization (CISH) and immunohistochemistry for molecular classification (types germinal center B cells - GCB X activated - ABC). Of the 80 cases analyzed, 3 were CISH EBV+ (3.75%). All 3 patients had more than 50 years, and two were men (stomach and bone marrow) and a woman (mediastinum). Molecular classification according to Hans´ algorithm showed the following types: ABC = 1, GCB = 1 and 1 was not rated. EBV+ DLBCL is characterized by the activation of the classical and alternative pathways of NF-kB, most cases showing ABC pattern, prevalence in patients over 50 years and predominance of extra-nodal location. These characteristics were observed in the present series. Despite all positive cases in this TMA correspond to patients over 50 years, the arbitrary cut-off point and the growing number of cases in younger patients justify the tendency towards the abolition of the term “of the elderly” in the next WHO classification review. In conclusion, recognition of EBV+ DLBCL, regardless of age, is important because new therapeutic approaches targeting EBV and the NFkB pathway can be used in these patients, which has worst prognosis.

Biography:

Dr Munaf Desai completed MD in pathology in 1995 from BJMC Ahmadabad, India. He is a Specialist in histopathology and head of histopathology cytology unit at Al Qassimi Hospital Sharjah, UAE.

Abstract:

Introduction/background: Total 174 cases of Breast CNB were received from 2 different sources i.e. National Screening Centre, Abu Dhabi (168) and Sharjah Kuwaiti Hospital (6). The cases were mixed either palpable or non-palpable (screen detected) from patients’ age ranging from 32 to 73 years. 56 patients were the nationals of United Arab Emirates and the rest were from about 20 different nationalities. The types of the procedures of biopsy taking were variable like core needle or vacuum assisted either U/S guided or stereotactic mammogram guided. Method: Total 174 cases received during this period were analyzed. H & E stain on 3 levels was done in all the cases. Immunohistochemistry for breast progressive markers ER, PR & Her2neu was done on all malignant cases. Immunohistochemistry markers E-cadherin, CKAE1AE3, Collagen IV, SMA, SMM-HC, P63, CD10, HMWCK, and Ki67 were run as per the requirement based on H & E findings and availability in the department. CD31, S100, CD34, Desmin, bcl2, CD99 and CD45 were also used on rare occasions. Result: Definite benign diagnosis was given in 43 cases without use of IHC. 37 definite malignant diagnoses were given without using myoepithelial markers. Myoepithelial markers were used in 81 cases, 58 out of them were concluded as benign and 23 as malignant. Schwannoma and vascular neoplasms were ruled out in few cellular fibroepithelial lesions by use of CD31, S100, CD34 and Desmin. Cases of radial scar, complex sclerosing lesion and some sclerosing adenosis were mimicking invasive carcinoma on H&E examination. Here myoepithelial markers helped to reach the final diagnosis. In other instances, CKAE1AE3 and CD45 were useful to rule out lobular invasive component where lymphocytes were causing confusion. Myoepithelial /basal markers and ER also helped in papillary lesions. HMWCK helped in differentiating usual ductal hyperplasia from atypical ductal hyperplasia. ER and ki67 were useful in columnar cell lesion. Conclusion: In few cases of Breast CNB, definite diagnosis is not possible without IHC. Diagnostic problems in lesions like radial scar, complex sclerosing lesion, columnar cell lesions/flat epithelial atypia, atypical ductal hyperplasia and papillary lesion; myoepithelial markers, ER and HMWCK are useful to reach the final diagnosis. Use of breast progressive markers on carcinoma diagnosed on CNB is of tremendous importance for very small lesions and for possible mixed tumours. Also they are almost compulsory where the CNB and followed excision/mastectomy are performed and diagnosed at two different centres.

Biography:

Prof Sujata Jetleyis a graduate & postgraduate of Armed Forces Medical College, Pune.She has been actively involved in teaching undergraduate & postgraduate students. Her present appointment is Professor, Dept of Pathology, Hamdard Institute of Medical Sciences &Research, Jamia Hamdard, New Delhi. She has comprehensive experience in all aspects of pathology, and has guided many research projects, both as supervisor and co-supervisor. Her field of interest is tumor biology and gynecologic pathology. She is a recognized postgraduate teacher & guide in Pathology for Pune University & the Maharashtra University of Health Sciences. Publications (Indexed National & International Journals) -36

Abstract:

Tuberculosis is a major cause of morbidity and mortality in the developing world and remains a leading public health problem worldwide. It is known to coexist with various disease processes and an awareness of unusual clinical presentations mimicking diverse conditions, as seen in this series, highlight the importance of a high index of suspicion in the timely diagnosis of tuberculosis. Case 1: Fever with axillary lymphadenopathy, clinical impression: Tuberculosis. Final diagnosis: Coexistent axillary hydatid disease and tuberculosis. Case 2: Fever with nodular erythematous rashes, clinical impression: Hansen’s disease. Final diagnosis: Coexistent Erythema Nodosum Leprosum and tubercular lymphadenitis. Case 3: Irregular growth cervix, bleeds on touch, clinical impression: Carcinoma cervix. Finaldiagnosis: Tuberculosis cervix. Case 4: Tenderness & swelling left breast, 15 days duration, clinical impression: Breast abscessFinal diagnosis: Tuberculosis breast. Case 5: Hoarseness of voice 2 years duration, clinical impression: Carcinoma larynx. Final diagnosis: Spindle cell carcinoma larynx with tubercular lymphadenitis. All cases demonstrated characteristic epithelioid cell granulomas with or without necrosis along with ZiehlNeelson staining and culture positivity except case 5 which was negative and molecular techniques were used for diagnosis. All patients were placed on anti-tubercular treatment with good response on regular follow up. Tuberculosis, today, is a re-emerging disease with a changing epidemiology. Evidence of systemic or lung involvement is not always present. Laboratory findings and radiological findings play an important role in the evaluation. Definitive tissue diagnosis along with demonstration of AFB and isolation in cultures or by molecular techniques remains the gold standard.

Biography:

Abstract:

Objectives: To estimate the reliability of flow cytometry in the early classification of childhood acute lymphoblastic leukemia (B-ALL) and to analyze the causes of discrepancies between the DNA index by flow cytometry (DNAI-FCM) and the cytogenetic studies (CG) ;(Karyotype and Fluorescent in Situ Hybridization; FISH). Methods: DNAI-FCM and CG (Karyotype and FISH) were analyzed in 69 consecutive children, newly diagnosed with acute B-lymphoblastic leukemia (B-ALL) in King Faisal Specialist Hospital between the years 2012 and 2014. Results: A statistically significant correlation existed between DNAI-FCM and CG (p = 0.001). DNAI-FCM was proportional to CG in (57/69) 82.6% of the cases. There was a discrepancy between the DNAI-FCM and the CG in (12/69) 17.4% of the cases. Ten cases had a DNAI-FCM of 1 and were hyperdiploid (47-50) by karyotype and/or FISH, one case had a DNAI-FCM of 0.8 with a diploid karyotype and hyperdiploid by FISH. One case had DNAI-FCM of 1.14 and diploid karyotype while FISH was not done. In studying these cases, three cases showed a hyperdiploid karyotype detected in less than 10% of the cells by FISH or small number of cells by karyotype. One case had DNAI-FCM of 1.14, karyotype revealed a diploid number of chromosomes in 4 cells, while FISH was not done due to insufficient quantity. Four cases exhibit trisomy or tetrasomy 21 in almost 100% of the cells by FISH, while compared to the matching cases 24/ 57 have extra copies of chromosome 21. These extra copies in 22/24 are exclusively along with extra copies of chromosome 4,10,17. 2/24 , karyotype was not done and they were negative for the B-ALL FISH panel. Trisomy 4,10,17 are detected in (47-50) hyperdiploid cases. The cause of the discrepancy in the remaining 4 cases was not clear Conclusion: DNAI-FCM is 82.6% reliable in the early classification of childhood B-ALL with a predictive value of 81%. Discrepancies do occur in 17.4%. In 66.66% this mismatch refers to either the small size of the chromosome or to an insufficient genetic material representing abnormality.

Biography:

Based on his engineering background, his research has involved finding alternative solutions to challenging research questions. He’s published 15 papers in high impact journals, 2 book chapters and 7 conference papers. In 2008 he was awarded the Armaund Blanc young researcher of the year award in advance of the awarding of his PhD in 2009. He has worked in commercially based research in the University of Manchester and his current role is Senior Research Fellow: FASTPATH: Fast-Tracking Pathology via Automated Image Analysis and High-Performance Computing: Application to Prostate Cancer Diagnostics (Marie Curie IAPP (FP7)). University College Dublin, Ireland

Abstract:

There are a number of dilemmas in the diagnosis and treatment of prostate cancer. Current strategies result in overtreatment of indolent disease due to their inability to determine if a tumor will progress. Image analysis offers a mechanism for objective, reproducible and repeatable biopsy interpretation and also the extraction of novel biomarkers imperceptible to the human eye. Thus, adding further information to stratify patients into appropriate treatments. The Irish Prostate Cancer Research Consortium cohort was used for re-interpreting digital colour images of prostate tissue sections. The patientoutcomes of this cohort are known (Indolent, Significant or Aggressive) as well clinical information (PSA, family history, DRE, needle biopsyGleason Score, Age). Novel image tissue features of entropy and symmetric wavelets were calculated on local and overall tissue level. Similarly cell nuclei size and distributions were calculated along with luminal and stromal distributions. Using k-Nearest Neighbours and Neural Network models correct classification rates of patient outcomes based on clinical datasets (53%), image datasets (49%) and the merged datasets (56%) were computed for Indolent, Significant or Aggressive disease. Similarly patient outcomes based on clinical datasets (79%), image datasets (77%) and the merged datasets (84%) were computed for Indolent or non-Indolent disease. Thus, indicating that the novel image features are synergeticwith clinical data in separating patients with or without a significant cancer. These image features add value to the current clinical features and could be used to reduce the over treatment of prostate cancer and increase the quality of life of these patients