Gastroenterology Commons^™

Blockade Of Fibroblast Activation Protein In Combination With Radiation Treatment In Murine Models Of Pancreatic Adenocarcinoma., Andrew J Gunderson, Tomoko Yamazaki, Kayla Mccarty, Michaela Phillips, Alejandro F Alice, Shelly Bambina, Lauren Zebertavage, David Friedman, Benjamin Cottam, Pippa Newell, Michael J. Gough, Marka R Crittenden, Pieter Van Der Veken, Kristina H Young

Articles, Abstracts, and Reports

Pancreatic ductal adenocarcinoma (PDAC) is characterized by a fibrotic stroma with a poor lymphocyte infiltrate, in part driven by cancer-associated fibroblasts (CAFs). CAFs, which express fibroblast activation protein (FAP), contribute to immune escape via exclusion of anti-tumor CD8+ T cells from cancer cells, upregulation of immune checkpoint ligand expression, immunosuppressive cytokine production, and polarization of tumor infiltrating inflammatory cells. FAP is a post-proline peptidase selectively expressed during tissue remodeling and repair, such as with wound healing, and in the tumor microenvironment by cancer-associated fibroblasts. We targeted FAP function using a novel small molecule inhibitor, UAMC-1110, and mice with germline knockout …

Economical Effect Of Lumen Apposing Metal Stents For Treating Benign Foregut Strictures., Alexander Hallac, Wichit Srikureja, Eashen Liu, Parag Dhumal, Ashish Thatte, Nishant Puri

Articles, Abstracts, and Reports

AIM: To evaluate the clinical and economical efficacy of lumen apposing metal stent (LAMS) in the treatment of benign foregut strictures.

METHODS: A single center retrospective database of patients who underwent endoscopic treatment of benign foregut strictures between January 2014 and May 2017 was analyzed. A control group of non-stented patients who underwent three endoscopic dilations was compared to patients who underwent LAMS placement. Statistical tests performed included independent

RESULTS: Nine hundred and ninety-eight foregut endoscopic dilations were performed between January 2014 and May 2017. 15 patients underwent endoscopic LAMS placement for treatment of benign foregut stricture. Thirty-six patients with …

Cardiac Mri T2* In Liver Transplant Candidates: Application And Performance Of A Novel Imaging Technique To Identify Patients At Risk For Poor Posttransplant Cardiac Outcomes., Sara M Lewin, Kimberly Kallianos, M Ilan Nevah, Susan Zhao, Oren K Fix, Gabriel C Brooks, Teresa De Marco, Atif N Qasim, Karen G Ordovas, Neil Mehta

Articles, Abstracts, and Reports

Background: In end-stage liver disease, alterations in iron metabolism can lead to iron overload and development of iron overload cardiomyopathy. In liver transplant candidates, evaluation for cardiac iron overload and dysfunction can help to identify candidates at increased risk for peritransplant morbidity and mortality, though recommendations for pretransplant evaluation of cardiac iron overload are not standardized. Cardiac Magnetic Resonance Imaging T2* (CMRI-T2*) is a validated method to quantify cardiac iron deposition, with normal T2* value of 20 ms or greater. In this study, we sought to identify the incidence and predictors of iron overload by CMRI-T2* and to evaluate the …

Complement Factor D Protects Mice From Ethanol-Induced Inflammation And Liver Injury., Rebecca L Mccullough, Megan R Mcmullen, Megan M Sheehan, Kyle L Poulsen, Sanjoy Roychowdhury, Dian J Chiang, Michele T Pritchard, Juan Caballeria, Laura E Nagy

Articles, Abstracts, and Reports

Complement plays a crucial role in microbial defense and clearance of apoptotic cells. Emerging evidence suggests complement is an important contributor to alcoholic liver disease. While complement component 1, Q subcomponent (C1q)-dependent complement activation contributes to ethanol-induced liver injury, the role of the alternative pathway in ethanol-induced injury is unknown. Activation of complement via the classical and alternative pathways was detected in alcoholic hepatitis patients. Female C57BL/6J [wild type (WT)], C1q-deficient ( C1qa

A Randomized, Placebo-Controlled Trial Of Cenicriviroc For Treatment Of Nonalcoholic Steatohepatitis With Fibrosis., Scott L Friedman, Vlad Ratziu, Stephen A Harrison, Manal F Abdelmalek, Guruprasad P Aithal, Juan Caballeria, Sven Francque, Geoffrey Farrell, Kris V Kowdley, Antonio Craxi, Krzysztof Simon, Laurent Fischer, Liza Melchor-Khan, Jeffrey Vest, Brian L Wiens, Pamela Vig, Star Seyedkazemi, Zachary Goodman, Vincent Wai-Sun Wong, Rohit Loomba, Frank Tacke, Arun Sanyal, Eric Lefebvre

Articles, Abstracts, and Reports

The aim of this study was to evaluate cenicriviroc (CVC), a dual antagonist of CC chemokine receptor types 2 and 5, for treatment of nonalcoholic steatohepatitis (NASH) with liver fibrosis (LF). A randomized, double-blind, multinational phase 2b study enrolled subjects with NASH, a nonalcoholic fatty liver disease activity score (NAS) ≥4, and LF (stages 1-3, NASH Clinical Research Network) at 81 clinical sites. Subjects (N = 289) were randomly assigned CVC 150 mg or placebo. Primary outcome was ≥2-point improvement in NAS and no worsening of fibrosis at year 1. Key secondary outcomes were: resolution of steatohepatitis (SH) and no …

A Randomized Trial Of Obeticholic Acid Monotherapy In Patients With Primary Biliary Cholangitis., Kris V Kowdley, Velimir Luketic, Roger Chapman, Gideon M Hirschfield, Raoul Poupon, Christoph Schramm, Catherine Vincent, Christian Rust, Albert Parés, Andrew Mason, Hanns-Ulrich Marschall, David Shapiro, Luciano Adorini, Cathi Sciacca, Tessa Beecher-Jones, Olaf Böhm, Richard Pencek, David Jones

Articles, Abstracts, and Reports

Obeticholic acid (OCA), a potent farnesoid X receptor agonist, was studied as monotherapy in an international, randomized, double-blind, placebo-controlled phase 2 study in patients with primary biliary cholangitis who were then followed for up to 6 years. The goals of the study were to assess the benefit of OCA in the absence of ursodeoxycholic acid, which is relevant for patients who are intolerant of ursodeoxycholic acid and at higher risk of disease progression. Patients were randomized and dosed with placebo (n = 23), OCA 10 mg (n = 20), or OCA 50 mg (n = 16) given as monotherapy once …

Macrophage-Derived Il-1Β/Nf-Κb Signaling Mediates Parenteral Nutrition-Associated Cholestasis., Karim C El Kasmi, Padade M Vue, Aimee L Anderson, Michael W Devereaux, Swati Ghosh, Natarajan Balasubramaniyan, Sophie A Fillon, Carola Dahrenmoeller, Ayed Allawzi, Crystal Woods, Sarah Mckenna, Clyde J Wright, Linda Johnson, Angelo D'Alessandro, Julie A Reisz, Eva Nozik-Grayck, Frederick J Suchy, Ronald J Sokol

Articles, Abstracts, and Reports

In infants intolerant of enteral feeding because of intestinal disease, parenteral nutrition may be associated with cholestasis, which can progress to end-stage liver disease. Here we show the function of hepatic macrophages and phytosterols in parenteral nutrition-associated cholestasis (PNAC) pathogenesis using a mouse model that recapitulates the human pathophysiology and combines intestinal injury with parenteral nutrition. We combine genetic, molecular, and pharmacological approaches to identify an essential function of hepatic macrophages and IL-1β in PNAC. Pharmacological antagonism of IL-1 signaling or genetic deficiency in CCR2, caspase-1 and caspase-11, or IL-1 receptor (which binds both IL-1α and IL-1β) prevents PNAC in …

Upper And Lower Gastrointestinal Endoscopic Findings In Hiv-Infected Patients In The Era Of Highly Active Antiretroviral Therapy., Russell Parvin, Sindhura Kolli, Jamil Shah, Manan Jhaveri, Madhavi Reddy

Articles, Abstracts, and Reports

Background: Endoscopic evaluation with biopsies are instrumental in the diagnosis and management of gastrointestinal (GI) disorders in the setting of human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS), especially in the era of highly active antiretroviral therapy (HAART).

Methods: A retrospective chart review of 304 HIV-positive and 199 HIV-negative patients who had undergone upper and/or lower endoscopy in an urban community hospital from the years 2012 - 2017 was performed. Inclusion criteria included men and women between the ages of 45 to 75 years, which had undergone colonoscopies between within 2012 - 2017 and had tested positive for HIV. …

Extracorporeal Cellular Therapy (Elad) In Severe Alcoholic Hepatitis: A Multinational, Prospective, Controlled, Randomized Trial., Julie Thompson, Natasha Jones, Ali Al-Khafaji, Shahid Malik, David Reich, Santiago Munoz, Ross Macnicholas, Tarek Hassanein, Lewis Teperman, Lance Stein, Andrés Duarte-Rojo, Raza Malik, Talal Adhami, Sumeet Asrani, Nikunj Shah, Paul Gaglio, Anupama Duddempudi, Brian Borg, Rajiv Jalan, Robert Brown, Heather Patton, Rohit Satoskar, Simona Rossi, Amay Parikh, Ahmed Elsharkawy, Parvez Mantry, Linda Sher, David Wolf, Marquis Hart, Charles Landis, Alan Wigg, Shahid Habib, Geoffrey Mccaughan, Steven Colquhoun, Alyssa Henry, Patricia Bedard, Lee Landeen, Michael Millis, Robert Ashley, William Frank, Andrew Henry, Jan Stange, Ram Subramanian

Articles, Abstracts, and Reports

Severe alcoholic hepatitis (sAH) is associated with a poor prognosis. There is no proven effective treatment for sAH, which is why early transplantation has been increasingly discussed. Hepatoblastoma-derived C3A cells express anti-inflammatory proteins and growth factors and were tested in an extracorporeal cellular therapy (ELAD) study to establish their effect on survival for subjects with sAH. Adults with sAH, bilirubin ≥8 mg/dL, Maddrey's discriminant function ≥ 32, and Model for End-Stage Liver Disease (MELD) score ≤ 35 were randomized to receive standard of care (SOC) only or 3-5 days of continuous ELAD treatment plus SOC. After a minimum follow-up of …

Intracorporeal Versus Extracorporeal Anastomosis For Minimally Invasive Right Colectomy: A Multi-Center Propensity Score-Matched Comparison Of Outcomes., Robert K Cleary, Andrew Kassir, Craig S Johnson, Amir L Bastawrous, Mark K Soliman, Daryl S Marx, Luca Giordano, Tobi J Reidy, Eduardo Parra-Davila, Vincent J Obias, Joseph C Carmichael, Darren Pollock, Alessio Pigazzi

Articles, Abstracts, and Reports

BACKGROUND: The primary objective of this study was to retrospectively compare short-term outcomes of intracorporeal versus extracorporeal anastomosis for minimally invasive laparoscopic and robotic-assisted right colectomies for benign and malignant disease. Recent studies suggest potential short-term outcomes advantages for the intracorporeal anastomosis technique.

METHODS: This is a multicenter retrospective propensity score-matched comparison of intracorporeal and extracorporeal anastomosis techniques for laparoscopic and robotic-assisted right colectomy between January 11, 2010, and July 21, 2016.

RESULTS: After propensity score-matching, there were a total of 1029 minimal invasive surgery cases for analysis-379 right colectomies (335 robotic-assisted and 44 laparoscopic) done with an intracorporeal anastomosis …

Multisite Evaluation Of The Bd Max Extended Enteric Bacterial Panel For Detection Of Yersinia Enterocolitica, Enterotoxigenic Escherichia Coli, Vibrio, And Plesiomonas Shigelloides From Stool Specimens., Patricia J Simner, Margret Oethinger, Kathleen A Stellrecht, Dylan R Pillai, Ram Yogev, Helene Leblond, Joel Mortensen

Articles, Abstracts, and Reports

The purpose of this study was to perform a multisite evaluation to establish the performance characteristics of the BD Max extended enteric bacterial panel (xEBP) assay directly from unpreserved or Cary-Blair-preserved stool specimens for the detection of Yersinia enterocolitica, enterotoxigenic Escherichia coli (ETEC), Vibrio, and Plesiomonas shigelloides The study included prospective, retrospective, and prepared contrived specimens from 6 clinical sites. BD Max xEBP results were compared to the reference method, which included standard culture techniques coupled with alternate PCR and sequencing, except for ETEC, for which the reference method was two alternate PCRs and sequencing. Alternate PCR was …

Colonoscopy: Advanced And Emerging Techniques-A Review Of Colonoscopic Approaches To Colorectal Conditions., Anjali S Kumar, Jennifer Kim Lee

Articles, Abstracts, and Reports

A complete colonoscopy is key in the diagnostic and therapeutic approaches to a variety of colorectal diseases. Major challenges are incomplete polyp removal and missed polyps, particularly in the setting of a difficult colonoscopy. There are a variety of both well-established and newer techniques that have been developed to optimize polyp detection, perform complete polypectomy, and endoscopically treat various complications and conditions such as strictures and perforations. The objective of this article is to familiarize the colorectal surgeon with techniques utilized by advanced endoscopists.

Pancreaticoduodenectomy In A Patient With Previous Left Ventricular Assist Device: A Case Report With Specific Emphasis On Peri-Operative Logistics., Juan Mejia, Mei Dong, Okechukwu Ojogho

Articles, Abstracts, and Reports

To the best of our knowledge this is the first case of this nature described in the literature. Sharing the authors experience with this case, particularly the technical challenges and post-operative management may aid other physicians facing similar scenarios. In this report, we describe a pancreaticoduodenectomy for pancreatic adenocarcinoma in a patient with a previous left ventricular assist device (LVAD). A multidisciplinary approach, particularly close involvement of the advanced heart failure, mechanical heart and pancreas surgery teams was key to the success of this case. Major abdominal surgery in the setting of previous LVAD should be considered carefully, however, the …

New Developments In The Treatment Of Primary Biliary Cholangitis - Role Of Obeticholic Acid., Manan A Jhaveri, Kris V Kowdley

Articles, Abstracts, and Reports

Primary biliary cholangitis (PBC) is a chronic autoimmune cholestatic liver disease that predominantly affects women in early to middle age. It is typically associated with autoantibodies to mitochondrial antigens and results in immune-mediated destruction of small and medium-sized intrahepatic bile ducts leading to cholestasis, hepatic fibrosis and may progress to cirrhosis or hepatic failure and, in some cases, hepatocellular carcinoma. The clinical presentation and the natural history of PBC have improved over the years due to recognition of earlier widespread use of ursodeoxycholic acid (UDCA); about one-third of patients show suboptimal biochemical response to UDCA with poor prognosis. Until recently, …

Preoperative Immunonutrition And Elective Colorectal Resection Outcomes., Lucas W Thornblade, Thomas K Varghese, Xu Shi, Eric K Johnson, Amir Bastawrous, Richard P Billingham, Richard Thirlby, Alessandro Fichera, David R Flum

Articles, Abstracts, and Reports

BACKGROUND: Randomized controlled trials demonstrate the efficacy of arginine-enriched nutritional supplements (immunonutrition) in reducing complications after surgery. The effectiveness of preoperative immunonutrition has not been evaluated in a community setting.

OBJECTIVE: This study aims to determine whether immunonutrition before elective colorectal surgery improves outcomes in the community at large.

DESIGN: This is a prospective cohort study with a propensity score-matched comparative effectiveness evaluation.

SETTINGS: This study was conducted in Washington State hospitals in the Surgical Care Outcomes Assessment Program from 2012 to 2015.

PATIENTS: Adults undergoing elective colorectal surgery were selected.

INTERVENTIONS: Surgeons used a preoperative checklist that recommended that …

Histopathology And Enhanced Detection Of Tumor Invasion Of Peritoneal Membranes., Jey-Hsin Chen, Melissa Borges

Articles, Abstracts, and Reports

Tumor invasion of the peritoneal membrane may have an adverse prognostic significance, but its histopathologic features can be diagnostically difficult to recognize. We observed that local peritoneal injury associated with tumor invasion is characterized by activation and proliferation of serosal stromal cells that express cytokeratin, a characteristic property of injured serosal membranes that may have diagnostic utility. To explore this, we examined 120 primary tumors of the gastrointestinal tract and pancreaticobiliary system using cytokeratin and elastic stains to assess for tumor invasion of peritoneal membranes. Peritoneal invasion by tumor was associated with retraction, splaying, and destruction of the elastic lamina …