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Segmental Distribution Of Hepatocellular Carcinoma Correlates With Microvascular Invasion In Liver Explants Undergoing Transplantation, Yasir Al-Azzawai, Eva Rouanet, Ryan J. Hendrix, Lidia Spaho, Hesham Malik, Deepika Devuni, Gyongyi Szabo, Graham Barnard 2019 University of Massachusetts Medical School

Segmental Distribution Of Hepatocellular Carcinoma Correlates With Microvascular Invasion In Liver Explants Undergoing Transplantation, Yasir Al-Azzawai, Eva Rouanet, Ryan J. Hendrix, Lidia Spaho, Hesham Malik, Deepika Devuni, Gyongyi Szabo, Graham Barnard

Gyongyi Szabo

Introduction: Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients is a poor prognostic factor after liver transplantation and/or resection. Any correlation between MVI and segmental location of HCC has yet to be studied. Our aim is to evaluate the segmental location of HCC and any correlation with the presence of MVI, portal vein thrombosis (PVT) in explanted livers, and the recurrence of HCC after transplantation. Another objective of the study is to assess the treatment history (ablation or transarterial chemoembolization (TACE)) and size of the tumor with respect to the risk of MVI.

Methods: A single center, retrospective chart ...


Segmental Distribution Of Hepatocellular Carcinoma Correlates With Microvascular Invasion In Liver Explants Undergoing Transplantation, Yasir Al-Azzawai, Eva Rouanet, Ryan J. Hendrix, Lidia Spaho, Hesham Malik, Deepika Devuni, Gyongyi Szabo, Graham Barnard 2019 University of Massachusetts Medical School

Segmental Distribution Of Hepatocellular Carcinoma Correlates With Microvascular Invasion In Liver Explants Undergoing Transplantation, Yasir Al-Azzawai, Eva Rouanet, Ryan J. Hendrix, Lidia Spaho, Hesham Malik, Deepika Devuni, Gyongyi Szabo, Graham Barnard

Open Access Articles

Introduction: Microvascular invasion (MVI) in hepatocellular carcinoma (HCC) patients is a poor prognostic factor after liver transplantation and/or resection. Any correlation between MVI and segmental location of HCC has yet to be studied. Our aim is to evaluate the segmental location of HCC and any correlation with the presence of MVI, portal vein thrombosis (PVT) in explanted livers, and the recurrence of HCC after transplantation. Another objective of the study is to assess the treatment history (ablation or transarterial chemoembolization (TACE)) and size of the tumor with respect to the risk of MVI.

Methods: A single center, retrospective chart ...


Rare Sarcomatoid Carcinoma Of The Liver In A Patient With No History Of Hepatocellular Carcinoma: A Case Report, Kevat B. Patel, Rita H. Hawarny, Elizabeth Saunders, Marc Hettlinger, Niru Nahar 2019 Joan C. Edwards School of Medicine, Marshall University

Rare Sarcomatoid Carcinoma Of The Liver In A Patient With No History Of Hepatocellular Carcinoma: A Case Report, Kevat B. Patel, Rita H. Hawarny, Elizabeth Saunders, Marc Hettlinger, Niru Nahar

Marshall Journal of Medicine

Sarcomatoid carcinoma is a rare malignant tumor of unknown pathogenesis characterized by poorly differentiated carcinoma tissue containing sarcoma-like differentiation of either spindle or giant cell and rarely occurs in the gastrointestinal tract and hepatobiliary-pancreatic system.1 Primary hepatic sarcomatoid carcinoma accounts for only 0.2 % of primary malignant liver tumors, and 1.8% of all surgically resected hepatocellular carcinomas.2 The majority of hepatic sarcomatoid carcinoma cases appear to occur simultaneously with hepatocellular or cholangiocellular carcinoma.3 The preferred treatment for hepatic sarcomatoid carcinoma is surgical resection and the overall prognosis is poor.4 This case depicts a 62-year-old female ...


Aortoduodenal Fistula Forms From Primary Aortic Stump Graft In A Two-Time Multi-Visceral Transplant Patient With Presentation Of Gastrointestinal Bleed And Bowel Perforation: A Case Report, Brielle Corrente 2019 Duquesne University

Aortoduodenal Fistula Forms From Primary Aortic Stump Graft In A Two-Time Multi-Visceral Transplant Patient With Presentation Of Gastrointestinal Bleed And Bowel Perforation: A Case Report, Brielle Corrente

Graduate Student Research Symposium

Usually not diagnosed until open laparotomy, aortoduodenalfistulas (ADF) are one of the rarest complications of intestinal transplant surgery. With an incidence rate of only 0.04% at autopsy and only 250 documented cases since the early 1800’s, aortoduodenal fistulas are the most deadly complications of intestinal transplantation with a mortality rate of 100% without surgical intervention. A 39 year old, two-time multi-visceral transplant African American female patient suffered from a primary aortoduodenal fistula formation in a primary modified multi-visceral transplant aortic stump graft site. With emergency open laparotomy repair, revascularization of the secondary multi-visceral transplant was performed, saving the ...


Extracellular Vesicles In Liver Diseases: Meeting Report From The International Liver Congress 2018, Jesus M. Banales, Ariel E. Feldstein, Hanna Sanger, Veronika Lukacs-Kornek, Gyongyi Szabo, Miroslaw Kornek 2019 University of the Basque Country

Extracellular Vesicles In Liver Diseases: Meeting Report From The International Liver Congress 2018, Jesus M. Banales, Ariel E. Feldstein, Hanna Sanger, Veronika Lukacs-Kornek, Gyongyi Szabo, Miroslaw Kornek

Gyongyi Szabo

Extracellular vesicles (EVs) are small and heterogeneous membrane-bound structures released by cells and found in all biological fluids. They are effective intercellular communicators, acting on a number of close and/or distant target cells. EV cargo may reflect the cell of origin as well as the specific stress that induces their formation and release. They transport a variety of bioactive molecules, including messenger RNA, noncoding RNAs, proteins, lipids, and metabolites, that can be transferred among cells, regulating various cell responses. Alteration in the concentration and composition of EVs in biological fluids is a typical hallmark of pathologies in different liver ...


Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo 2019 University of Massachusetts Medical School

Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo

Gyongyi Szabo

Alcoholic liver disease (ALD) is characterized by macrophage and neutrophil leukocyte recruitment and activation in the liver. Damage- and pathogen-associated molecular patterns contribute to a self-perpetuating proinflammatory state in ALD. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a surface receptor that amplifies inflammation induced by toll-like receptors (TLRs) and is expressed on neutrophils and monocytes/macrophages. We hypothesized that TREM-1 signaling contributes to proinflammatory pathway activation in ALD. Using an in vivo ALD model in mice, we tested the effects of ligand-independent TREM-1 inhibitory peptides that were formulated into human high-density lipoprotein (HDL)-mimicking complexes GF9-HDL and GA ...


A Multicenter Evaluation Of A New Eus Core Biopsy Needle: Experience In 200 Patients., Douglas G. Adler, V. Raman Muthusamy, Dean S. Ehrlich, Gulshan Parasher, Nirav C. Thosani, Ann Chen, Jonathan M. Buscaglia, Anoop Appannagari, Eduardo Quintero, Harry Aslanian, Linda Jo Taylor, Ali Siddiqui 2019 University of Utah School of Medicine

A Multicenter Evaluation Of A New Eus Core Biopsy Needle: Experience In 200 Patients., Douglas G. Adler, V. Raman Muthusamy, Dean S. Ehrlich, Gulshan Parasher, Nirav C. Thosani, Ann Chen, Jonathan M. Buscaglia, Anoop Appannagari, Eduardo Quintero, Harry Aslanian, Linda Jo Taylor, Ali Siddiqui

Division of Gastroenterology and Hepatology Faculty Papers

Background and Objectives: We present a multicenter study of a new endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) needle (Acquire, Boston Scientific, Natick, MA). The aim of the study was to analyze the needle's clinical performance when sampling solid lesions and to assess the safety of this device.

Methods: We performed a multicenter retrospective study of patients undergoing EUS-FNB during July 1-November 15, 2016.

Results: Two hundred patients (121 males and 79 females) underwent EUS-FNB of solid lesions with the Acquire needle. Lesions included solid pancreatic masses (n = 109), adenopathy (n = 45), submucosal lesions (n = 34), cholangiocarcinoma (n = 8), liver lesions ...


Cellular Senescence And Their Role In Liver Metabolism In Health And Disease: Overview And Future Directions, Matthew Schade, Jacqueline A. Sanabria, Rodrigo Aguilar, Milad Modarresi, Brad Gillon, Zach Hunter, Jacqueline Fannin, Amrita Mallick, Henri Brunengraber, Juan Sanabria 2019 Marshall University

Cellular Senescence And Their Role In Liver Metabolism In Health And Disease: Overview And Future Directions, Matthew Schade, Jacqueline A. Sanabria, Rodrigo Aguilar, Milad Modarresi, Brad Gillon, Zach Hunter, Jacqueline Fannin, Amrita Mallick, Henri Brunengraber, Juan Sanabria

Juan R. Sanabria

Chronic liver disease has globally risen mainly due to a prevalent Hepatitis C Virus (HCV) infection rate and an epidemic of obesity. It is estimated by the year 2030, 2.2 billion people around the world will be overweight and 1.1 billion people will be obese. Diabetes and obesity are the main risk factors for the development of the metabolic syndrome and in the liver of Non-Alcoholic Fatty Liver Disease (NAFLD) which could progress to NASH related cirrhosis and liver malignancy. At present there is not effective therapy for NASH besides loss of weight and exercise. Furthermore, optimal management ...


Extracellular Vesicles In Liver Diseases: Meeting Report From The International Liver Congress 2018, Jesus M. Banales, Ariel E. Feldstein, Hanna Sanger, Veronika Lukacs-Kornek, Gyongyi Szabo, Miroslaw Kornek 2019 University of the Basque Country

Extracellular Vesicles In Liver Diseases: Meeting Report From The International Liver Congress 2018, Jesus M. Banales, Ariel E. Feldstein, Hanna Sanger, Veronika Lukacs-Kornek, Gyongyi Szabo, Miroslaw Kornek

Open Access Articles

Extracellular vesicles (EVs) are small and heterogeneous membrane-bound structures released by cells and found in all biological fluids. They are effective intercellular communicators, acting on a number of close and/or distant target cells. EV cargo may reflect the cell of origin as well as the specific stress that induces their formation and release. They transport a variety of bioactive molecules, including messenger RNA, noncoding RNAs, proteins, lipids, and metabolites, that can be transferred among cells, regulating various cell responses. Alteration in the concentration and composition of EVs in biological fluids is a typical hallmark of pathologies in different liver ...


3d Printed Biliary Anatomy For Surgical Planning, Jason Core, Erik Massenzio, Tamar Wasserman, Kevin Xie 2019 Thomas Jefferson University

3d Printed Biliary Anatomy For Surgical Planning, Jason Core, Erik Massenzio, Tamar Wasserman, Kevin Xie

Phase 1

Background: Studies demonstrated that 3D-printed livers from CT or MRI data can be accurate models of actual patient anatomy. However, it has yet to be established if 3D printing offers improvements to clinical outcomes in surgery. This project seeks to optimize these applications for use at Jefferson by producing 3D-printed models from patient CT scans to guide liver resection surgeries.

Methods: A liver transplant attending was interviewed about challenges encountered during hepatectomies. A publicly available abdominal computed tomography scan was used to render a liver and its vasculature in 3DSlicer. The liver surface was cut into two halves in MeshMixer ...


Checkpoint Inhibitors: What Gastroenterologists Need To Know., Monjur Ahmed 2018 Thomas Jefferson University

Checkpoint Inhibitors: What Gastroenterologists Need To Know., Monjur Ahmed

Division of Gastroenterology and Hepatology Faculty Papers

Checkpoint inhibitors are increasingly being used in clinical practice. They can cause various gastrointestinal, hepatic and pancreatic side effects. As these side effects can be serious, appropriate management is essential. The different checkpoint inhibitors with their mechanisms of action and indications, as well as evaluation and management of gastrointestinal, hepatic and pancreatic side effects, are discussed in this article.


Surveillance, Prevention And Surgical Treatments For Hepatocellular Carcinoma, Kerui Xu 2018 University of Nebraska Medical Center

Surveillance, Prevention And Surgical Treatments For Hepatocellular Carcinoma, Kerui Xu

Theses & Dissertations

Liver cancer is the second-leading cause of cancer death, representing roughly 9.1% of all cancer mortality. Of all primary cancers of the liver, hepatocellular carcinoma (HCC) accounts for roughly 85%. HCC has been increasing in the U.S. and other countries. In particular, HCC places a huge burden on the Chinese population, as China alone consists of approximately 50% of the total HCC cases and deaths. In China, chronic hepatitis B virus (HBV) infection is the leading cause for developing HCC. The two challenges in prevention and control of HCC experienced in China are low rates of HCC screening ...


The Continuing Epidemic Of Hepatitis C In The United States: The Case Of West Virginia, David P. Paul III, Neha Botre, Maggie Phillips, Jumana Abboud, Alberto Coustasse 2018 Marshall University

The Continuing Epidemic Of Hepatitis C In The United States: The Case Of West Virginia, David P. Paul Iii, Neha Botre, Maggie Phillips, Jumana Abboud, Alberto Coustasse

Alberto Coustasse, DrPH, MD, MBA, MPH

Hepatitis C virus (HCV) is one of the most significant public health problems currently facing the U.S. If it is left untreated, the likelihood of sustaining a treatment response decreases. While early identification has been identified as a critical focus in trying to obtain better health outcomes, new drug treatments appear quite promising.


A Comparison Of Screening, Prevention, And Management For Hepatitis B Patients Between The Us And Chinese Healthcare Systems, Thomas Chen, James D. Plumb, MD 2018 Thomas Jefferson University

A Comparison Of Screening, Prevention, And Management For Hepatitis B Patients Between The Us And Chinese Healthcare Systems, Thomas Chen, James D. Plumb, Md

Phase 1

Introduction: Hepatitis B (HBV) is a complex disease entity with potentially serious outcomes, including developing hepatocellular carcinoma (HCC). HBV is estimated to be responsible for about 50-80% of HCC cases worldwide, and 75-95% of HCC cases in HBV endemic regions.1 HBV and HCC are great concerns especially in East Asian countries like China. In China, HCC ranks as the 2nd most common cancer and 2nd in cancer mortality, both behind only lung cancer.1 China is considered an endemic HBV region, with about 100-150 million people infected. In comparison, only an estimated 550,000-2 million people are ...


Sofosbuvir, Velpatasvir, And Voxilaprevir For Treatment Of Recurrent Hepatitis C Virus Infection After Liver Transplantation., Maria G Cardona-Gonzalez, Jason D Goldman, Lawrence Narayan, Diana M Brainard, Kris V Kowdley 2018 Division of Infectious Diseases Swedish Medical Center Seattle WA.

Sofosbuvir, Velpatasvir, And Voxilaprevir For Treatment Of Recurrent Hepatitis C Virus Infection After Liver Transplantation., Maria G Cardona-Gonzalez, Jason D Goldman, Lawrence Narayan, Diana M Brainard, Kris V Kowdley

Articles, Abstracts, and Reports

There are limited data on direct-acting antiviral (DAA) treatment options for previously treated patients with recurrent genotype 3 (GT3) hepatitis C virus (HCV) after liver transplantation. Sofosbuvir/velpatasvir/voxilaprevir (SOF/VEL/VOX) is currently approved for treatment of HCV in patients with prior treatment with DAAs. We report the first published experience using SOF/VEL/VOX after liver transplantation for a DAA-experienced patient with severe hepatitis due to early recurrent GT3 HCV. The patient was treated with SOF/VEL/VOX that was extended to a total duration of 16 weeks and was intensified with ribavirin (RBV) starting at week 8 ...


The Dynamic Roles Of Mesenchymal Stem Cells In Colon Cancer, Shan Wang, Zhiguo Miao, Qiyuan Yang, Yimin Wang, Jinzhou Zhang 2018 Henan Institute of Science and Technology

The Dynamic Roles Of Mesenchymal Stem Cells In Colon Cancer, Shan Wang, Zhiguo Miao, Qiyuan Yang, Yimin Wang, Jinzhou Zhang

Open Access Articles

Colon cancer is still one of the most common causes of cancer in human and is characterized by lymphocyte infiltrates and originates from the epithelial cells found in the lining of colon or rectum of the gastrointestinal tract. Mesenchymal stem cells (MSCs) are composed of the multipotent stem cell group of stroma and can be differentiated as various cell lineages, such as fibroblasts, osteoblasts, and adipocytes. MSCs provide mechanical and structural support and have potential functions during tumor growth and metastasis. The efficacy of MSC-based therapies is partly dependent on the migration and homing of MSCs to tumors and metastatic ...


Video Capsule Endoscopy In The Assessment Of Portal Hypertensive Enteropathy, Yasir Al-Azzawai, Lidia Spaho, Mohammed Mahmoud, Joan Kheder, Anne Foley, David R. Cave 2018 University of Massachusetts Medical School

Video Capsule Endoscopy In The Assessment Of Portal Hypertensive Enteropathy, Yasir Al-Azzawai, Lidia Spaho, Mohammed Mahmoud, Joan Kheder, Anne Foley, David R. Cave

Open Access Articles

Background: The features of the portal hypertension enteropathy (PHE) vary from mild mucosal changes to varices with or without bleeding. The prevalence and the development are not fully understood.

Aim: Our aim is to examine the prevalence and the different manifestations of PHE using video capsule endoscopy (VCE).

Methods: It is a single center retrospective study of patients with cirrhosis, who had VCE. Based on the published literature, we divided the PHE lesions into vascular lesions and mucosal lesions.

Results: Of the 100 patients with cirrhosis that had a VCE study, the mean age was 62.82 years. Male gender ...


Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo 2018 University of Massachusetts Medical School

Inhibition Of Triggering Receptor Expressed On Myeloid Cells 1 Ameliorates Inflammation And Macrophage And Neutrophil Activation In Alcoholic Liver Disease In Mice, David Tornai, Istvan Furi, Zu T. Shen, Alexander B. Sigalov, Sahin Coban, Gyongyi Szabo

Open Access Articles

Alcoholic liver disease (ALD) is characterized by macrophage and neutrophil leukocyte recruitment and activation in the liver. Damage- and pathogen-associated molecular patterns contribute to a self-perpetuating proinflammatory state in ALD. Triggering receptor expressed on myeloid cells 1 (TREM-1) is a surface receptor that amplifies inflammation induced by toll-like receptors (TLRs) and is expressed on neutrophils and monocytes/macrophages. We hypothesized that TREM-1 signaling contributes to proinflammatory pathway activation in ALD. Using an in vivo ALD model in mice, we tested the effects of ligand-independent TREM-1 inhibitory peptides that were formulated into human high-density lipoprotein (HDL)-mimicking complexes GF9-HDL and GA ...


Fxr And Tgr5 Agonists Ameliorate Liver Injury, Steatosis, And Inflammation After Binge Or Prolonged Alcohol Feeding In Mice, Arvin Iracheta-Vellve, Charles D. Calenda, Jan Petrasek, Aditya Ambade, Karen Kodys, Luciano Adorini, Gyongyi Szabo 2018 University of Massachusetts Medical School

Fxr And Tgr5 Agonists Ameliorate Liver Injury, Steatosis, And Inflammation After Binge Or Prolonged Alcohol Feeding In Mice, Arvin Iracheta-Vellve, Charles D. Calenda, Jan Petrasek, Aditya Ambade, Karen Kodys, Luciano Adorini, Gyongyi Szabo

Open Access Articles

Bile acids (BAs) activate various dedicated receptors, including the farnesoid X receptor (FXR) and the Takeda G protein-coupled receptor 5 (TGR5). The FXR agonist obeticholic acid (OCA) is licensed for the treatment of primary biliary cholangitis and has shown promising results in NASH patients, whereas TGR5 agonists target inflammation and metabolism. We hypothesized that FXR and/or TGR5 agonists may be therapeutic in early alcoholic liver disease (ALD) in mice, in which hepatic inflammation plays a major role. OCA, INT-777, and INT-767 are BA derivatives with selective agonist properties for FXR, TGR5, or both, respectively. These compounds were tested in ...


Microrna-96 Promotes Schistosomiasis Hepatic Fibrosis In Mice By Suppressing Smad7, Xufeng Luo, Dongmei Zhang, Jun Xie, Qin Su, Xing He, Ruipu Bai, Guangping Gao, Weiqing Pan 2018 Second Military Medical University

Microrna-96 Promotes Schistosomiasis Hepatic Fibrosis In Mice By Suppressing Smad7, Xufeng Luo, Dongmei Zhang, Jun Xie, Qin Su, Xing He, Ruipu Bai, Guangping Gao, Weiqing Pan

UMass Center for Clinical and Translational Science Supported Publications

Infection with Schistosoma causes aberrant expression of host microRNAs (miRNAs), and normalizing the levels of dysregulated miRNAs can attenuate pathology. Here, we show that the host miRNA, miR-96, is markedly upregulated during the progression of hepatic schistosomiasis. We demonstrate that elevation of miR-96 induces hepatic fibrosis in infected mice by suppressing the expression of its target gene, Smad7. We show that infection with Schistosoma induces the expression of transforming growth factor beta1 (TGF-beta1), which in turn upregulates the expression of miR-96 through SMAD2/3-DROSHA-mediated post-transcriptional regulation. Furthermore, inhibition of miR-96 with recombinant adeno-associated virus 8 (rAAV8)-mediated delivery of Tough ...


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