Digestive System Diseases Commons^™

Improved Survival After Liver Transplantation For Patients With Human Immunodeficiency Virus (Hiv) And Hiv/Hepatitis C Virus Coinfection In The Integrase Strand Transfer Inhibitor And Direct-Acting Antiviral Eras, Jake Sheraj Jacob, Anjiya Shaikh, Karthik Goli, Nicole E Rich, Jihane N Benhammou, Aijaz Ahmed, Donghee Kim, Abbas Rana, John A Goss, Susanna Naggie, Tzu-Hao Lee, Fasiha Kanwal, George Cholankeril

Faculty, Staff and Students Publications

BACKGROUND: People with human immunodeficiency virus (HIV) with and without hepatitis C virus (HCV) coinfection had poor outcomes after liver transplant (LT). Integrase strand transfer inhibitors (INSTIs) and direct-acting antivirals (DAAs) have changed the treatment landscape for HIV and HCV, respectively, but their impact on LT outcomes remains unclear.

METHODS: This retrospective analysis of adults with HIV monoinfection (n = 246) and HIV/HCV coinfection (n = 286) who received LT compared mortality in patients with HIV who received LT before versus after approval of INSTIs and in patients with HIV/HCV coinfection who received LT before versus after approval of DAAs. …

Single-Cell Sequencing Of Ascites Fluid Illustrates Heterogeneity And Therapy-Induced Evolution During Gastric Cancer Peritoneal Metastasis, Xuan-Zhang Huang, Min-Jiao Pang, Jia-Yi Li, Han-Yu Chen, Jing-Xu Sun, Yong-Xi Song, Hong-Jie Ni, Shi-Yu Ye, Shi Bai, Teng-Hui Li, Xin-Yu Wang, Jing-Yuan Lu, Jin-Jia Yang, Xun Sun, Jason C Mills, Zhi-Feng Miao, Zhen-Ning Wang

Faculty, Staff and Students Publications

Peritoneal metastasis is the leading cause of death for gastrointestinal cancers. The native and therapy-induced ascites ecosystems are not fully understood. Here, we characterize single-cell transcriptomes of 191,987 ascites cancer/immune cells from 35 patients with/without gastric cancer peritoneal metastasis (GCPM). During GCPM progression, an increase is seen of monocyte-like dendritic cells (DCs) that are pro-angiogenic with reduced antigen-presenting capacity and correlate with poor gastric cancer (GC) prognosis. We also describe the evolution of monocyte-like DCs and regulatory and proliferative T cells following therapy. Moreover, we track GC evolution, identifying high-plasticity GC clusters that exhibit a propensity to shift to a …

Survival Improvement For Patients With Metastatic Colorectal Cancer Over Twenty Years, Fadl A Zeineddine, Mohammad A Zeineddine, Abdelrahman Yousef, Yue Gu, Saikat Chowdhury, Arvind Dasari, Ryan W Huey, Benny Johnson, Bryan Kee, Michael S Lee, Maria Pia Morelli, Van K Morris, Michael J Overman, Christine Parseghian, Kanwal Raghav, Jason Willis, Robert A Wolff, Yoshikuni Kawaguchi, Jean-Nicolas Vauthey, Ryan Sun, Scott Kopetz, John Paul Shen

Faculty, Staff and Student Publications

Over the past two decades of successive clinical trials in metastatic colorectal cancer (CRC), the median overall survival of both control and experimental arms has steadily improved. However, the incremental change in survival for metastatic CRC patients not treated on trial has not yet been quantified. We performed a retrospective review of 1420 patients with de novo metastatic CRC who received their primary treatment at the University of Texas M.D. Anderson Cancer Center (UTMDACC) from 2004 through 2019. Median OS was roughly stable for patients diagnosed between 2004 and 2012 (22.6 months) but since has steadily improved for those diagnosed …

Hepatocytes Demarcated By Ephb2 Contribute To The Progression Of Nonalcoholic Steatohepatitis, Yang Xiao, Kirill Batmanov, Wenxiang Hu, Kun Zhu, Alexander Y Tom, Dongyin Guan, Chunjie Jiang, Lan Cheng, Sam J Mccright, Eric C Yang, Matthew R Lanza, Yifan Liu, David A Hill, Mitchell A Lazar

Faculty, Staff and Students Publications

Current therapeutic strategies for treating nonalcoholic steatohepatitis (NASH) have failed to alleviate liver fibrosis, which is a devastating feature leading to hepatic dysfunction. Here, we integrated single-nucleus transcriptomics and epigenomics to characterize all major liver cell types during NASH development in mice and humans. The bifurcation of hepatocyte trajectory with NASH progression was conserved between mice and humans. At the nonalcoholic fatty liver (NAFL) stage, hepatocytes exhibited metabolic adaptation, whereas at the NASH stage, a subset of hepatocytes was enriched for the signatures of cell adhesion and migration, which were mainly demarcated by receptor tyrosine kinase ephrin type B receptor …

Muc1 Expressions And Its Prognostic Values In Us Gastric Cancer Patients, Young-Il Kim, Robert Luke Pecha, Tara Keihanian, Michael Mercado, S Valeria Pena-Munoz, Kailash Lang, George Van Buren, Sadhna Dhingra, Mohamed O Othman

Faculty, Staff and Students Publications

This study aims to evaluate the prognostic value of MUC expression in US GC patients. A total of 70 tumor specimens were collected from GC patients who underwent surgery or endoscopic resection between 2013 and 2019 at a tertiary referral center in the US. MUC expression status including MUC1, MUC2, MUC5AC, and MUC6 was evaluated by immunohistochemical staining. The positive rates of MUC1, MUC2, MUC5AC, and MUC6 were 71.4%, 78.6%, 74.3%, and 33.3%, respectively. Patients with positive MUC1 expression had a significantly higher rate of aggressive pathologic features including diffuse-type cancer (42.0% vs. 0%; p < 0.001), advanced GC (80.0% vs. 30.0%, p < 0.001), lymph node metastasis (62.0% vs. 20.0%; p = 0.001), and …

Relief Of Malignant Gastric Outlet Obstruction With Lumen-Apposing Metallic Stent-Assisted Percutaneous Endoscopic Gastrostomy Tube After Roux-En-Y Gastric Bypass, Scott N Berger, Juan D Gomez Cifuentes, Tara Keihanian, Wasif M Abidi, Kalpesh K Patel

Faculty, Staff and Students Publications

No abstract provided.

The Spatial And Temporal Structure Of Neural Activity Across The Fly Brain, Katherine E Maturen, Cheri L Canon, Joel G Fletcher, Amy K Hara, David H Kim, Jonathan B Kruskal, Frank H Miller, Erick M Remer, Stuart G Silverman

Faculty, Staff and Student Publications

In 2012, the Society of Abdominal Radiology (SAR) was formed by the merger of the Society of Gastrointestinal Radiologists (SGR) and the Society of Uroradiology (SUR). On the occasion of SAR's ten year anniversary, this commentary describes important changes in society structure, the growth and diversity of society membership, new educational and research initiatives, intersociety and international outreach, and plans for the future.

Ct Colonography Is The Perfect Colorectal Screening Test That Unfortunately Few People Use Yet, David H Kim

Faculty, Staff and Student Publications

Take-home points

• • Computed tomography colonography (CTC) is the perfect test among the colorectal cancer screening options.
• • The excellent performance of CTC is on par with colonoscopy for both cancers and precancerous polyps, yet without the risks associated with perforation and sedation.
• • CTC presents an opportunity to serve as an important filter and send the small numbers of high-risk lesions for immediate removal while allowing the identification of the few true precursor targets from the large majority of benign polyps.
• • This selective polypectomy strategy at CTC minimizes complications and waste of resources while maintaining advanced neoplasia detection …

A Method Using Longitudinal Laboratory Data To Predict Future Intestinal Complication In Patients With Crohn's Disease, James Irwin, Anton Lord, Emma Ferguson, Lisa A Simms, Katherine Hanigan, Carlos A Montoya, Graham Radford-Smith

Faculty, Staff and Student Publications

Background

Stenosis, fistulization, and perforation of the bowel are severe outcomes which can occur in patients with Crohn’s disease. Accurate prediction of these events may enable clinicians to alter treatment strategies and avoid these outcomes.

Aims

To study the correlation between longitudinal laboratory testing and subsequent intestinal complications in patients with Crohn’s disease.

Methods

An observational cohort of patients with Crohn’s disease at a single center were analyzed between 01/01/1994 and 06/30/2016. A complication was defined as the development of an intestinal fistula, stenosis, or perforation. Exploratory analysis using Cox regression was performed to select the best statistical method to …

Eosinophils Protect Against Acetaminophen-Induced Liver Injury Through Cyclooxygenase-Mediated Il-4/Il-13 Production, Long Xu, Yang Yang, Jiali Jiang, Yankai Wen, Jong-Min Jeong, Christoph Emontzpohl, Constance L Atkins, Kangho Kim, Elizabeth A Jacobsen, Hua Wang, Cynthia Ju

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: A better understanding of the underlying mechanism of acetaminophen (APAP)-induced liver injury (AILI) remains an important endeavor to develop therapeutic approaches. Eosinophils have been detected in liver biopsies of patients with APAP overdose. We recently demonstrated a profound protective role of eosinophils against AILI; however, the molecular mechanism had not been elucidated.

APPROACH AND RESULTS: In agreement with our previous data from experiments using genetic deletion of eosinophils, we found that depletion of eosinophils in wild-type (WT) mice by an anti-IL-15 antibody resulted in exacerbated AILI. Moreover, adoptive transfer of eosinophils significantly reduced liver injury and mortality …

Automated In Vivo High-Resolution Imaging To Detect Human Papillomavirus-Associated Anal Precancer In Persons Living With Hiv, David Brenes, Alex Kortum, Jennifer Carns, Tinaye Mutetwa, Richard Schwarz, Yuxin Liu, Keith Sigel, Rebecca Richards-Kortum, Sharmila Anandasabapathy, Michael Gaisa, Elizabeth Chiao

Faculty, Staff and Students Publications

INTRODUCTION: In the United States, the effectiveness of anal cancer screening programs has been limited by a lack of trained professionals proficient in high-resolution anoscopy (HRA) and a high patient lost-to-follow-up rate between diagnosis and treatment. Simplifying anal intraepithelial neoplasia grade 2 or more severe (AIN 2+) detection could radically improve the access and efficiency of anal cancer prevention. Novel optical imaging providing point-of-care diagnoses could substantially improve existing HRA and histology-based diagnosis. This work aims to demonstrate the potential of high-resolution microendoscopy (HRME) coupled with a novel machine learning algorithm for the automated, in vivo diagnosis of anal precancer. …

Effect Of Liquid And Solid Test Meals On Symptoms And Gastric Myoelectrical Activity In Patients With Gastroparesis And Functional Dyspepsia, Kenneth L Koch, Mark Van Natta, Henry P Parkman, Madhusudan Grover, Thomas L Abell, Richard W Mccallum, Hossam A Shaltout, Irene Sarosiek, Gianrico Farrugia, Robert J Shulman, James Tonascia, Laura Miriel, Frank Hamilton, Pankaj J Pasricha, Gastroparesis Clinical Research Consortium

Faculty, Staff and Students Publications

BACKGROUND: Patients with gastroparesis (GP) and functional dyspepsia (FD) have similar symptoms, but the pathophysiology of postprandial symptoms remains uncertain.

AIMS: To compare symptoms and gastric myoelectrical activity (GMA) after liquid and solid test meals in patients with GP and FD.

METHODS: Patients enrolled in the Gastroparesis Clinical Research Consortium Registry were studied. Clinical characteristics were measured with standard questionnaires. GP was determined by 4-h solid-phase gastric scintigraphy. GMA was measured using electrogastrography before and after ingestion of a water load or nutrient bar on separate days. Symptoms were measured on visual analog scales. GMA responses to the water load …

Regulation Of Skeletal Muscle Protein Synthesis In The Preterm Pig By Intermittent Leucine Pulses During Continuous Parenteral Feeding, Marko Rudar, Agus Suryawan, Hanh V Nguyen, Shaji K Chacko, Caitlin Vonderohe, Barbara Stoll, Douglas G Burrin, Marta L Fiorotto, Teresa A Davis

Faculty, Staff and Students Publications

BACKGROUND: Extrauterine growth restriction is a common complication of preterm birth. Leucine (Leu) is an agonist for the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signaling pathway that regulates translation initiation and protein synthesis in skeletal muscle. Previously, we showed that intermittent intravenous pulses of Leu to neonatal pigs born at term receiving continuous enteral nutrition increases muscle protein synthesis and lean mass accretion. Our objective was to determine the impact of intermittent intravenous pulses of Leu on muscle protein anabolism in preterm neonatal pigs administered continuous parenteral nutrition.

METHODS: Following preterm delivery (on day 105 of 115 gestation), …

Rates Of Antimicrobial Resistance In Helicobacter Pylori Isolates From Clinical Trial Patients Across The Us And Europe, Francis Mégraud, David Y Graham, Colin W Howden, Ernest Trevino, Alice Weissfeld, Barbara Hunt, Neila Smith, Eckhard Leifke, William D Chey

Faculty, Staff and Students Publications

INTRODUCTION: Guidelines recommend that proton pump inhibitor-based triple regimens with clarithromycin not be used for Helicobacter pylori infection in areas where clarithromycin resistance is ≥15%, or in patients with prior macrolide use. Up-to-date information on local resistance patterns is limited, especially in the US. Here, we report resistance rates to antibiotics commonly used to treat H. pylori from a large study conducted in the US and Europe (pHalcon-HP).

METHODS: Gastric mucosal biopsies were collected from adult participants with H. pylori infection during screening. Minimum inhibitory concentrations were determined via agar dilution for clarithromycin, amoxicillin, and metronidazole, with breakpoints ≥1 μg/mL, …

A Single-Center Study Of Long-Term Effectiveness Of Vedolizumab In Anti-Tnf Refractory Pediatric Inflammatory Bowel Disease, Halee Patel, Lina Karam, Richard Kellermayer

Faculty, Staff and Students Publications

OBJECTIVES: Vedolizumab is an anti-α4β7 integrin antibody that has been used successfully in the treatment of adult-onset inflammatory bowel diseases (IBDs: Crohn disease [CD] and ulcerative colitis [UC]). Its off-label use in the pediatric IBD (PIBD) population is increasing, but knowledge on durability beyond 6 months of treatment is limited.

METHODS: A real-life, single-center, retrospective study of PIBD patients treated with vedolizumab was performed. Data on demographics, prior and concomitant treatments, and disease activity were obtained at 14 weeks, 26 weeks, 1 year, and 2 years of therapy. Primary outcome was corticosteroid- and other biologic-free remission (based on pediatric ulcerative …

Association Of Lifestyle Behaviors With Non-Alcoholic Fatty Liver Disease And Advanced Fibrosis Detected By Transient Elastography Among Hispanic/Latinos Adults In The Us, Natalia I Heredia, Xiaotao Zhang, Maya Balakrishnan, Jessica P Hwang, Aaron P Thrift

Faculty, Staff and Students Publications

OBJECTIVES: Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent liver disease, with the highest prevalence observed in the U.S. among Hispanic/Latino adults. While physical activity and dietary behaviors have established protective associations with NAFLD and its severity, these associations have not been well-characterized in Hispanic/Latino adults. The purpose of this study was to assess the association of lifestyle behaviors with NAFLD and advanced fibrosis in US Hispanic/Latino adults.

DESIGN: We selected all Hispanic/Latino adults from the 2017-2018 National Health and Nutrition Examination Survey (NHANES). NAFLD was defined as CAP ≥285 dB/m, and advanced fibrosis as liver stiffness measurements ≥8.6 …

The Performance Of Afp, Afp-3, Dcp As Biomarkers For Detection Of Hepatocellular Carcinoma (Hcc): A Phase 3 Biomarker Study In The United States, Nabihah Tayob, Fasiha Kanwal, Abeer Alsarraj, Ruben Hernaez, Hashem B El-Serag

Faculty, Staff and Students Publications

BACKGROUND & AIMS: α-fetoprotein (AFP), AFP Lens culinaris agglutinin-reactive fraction of AFP (AFP-L3), and des-gamma-carboxy prothrombin (DCP) in combination or in GALAD (Gender, Age, AFP-L3, AFP, and DCP) were tested for hepatocellular carcinoma (HCC) surveillance in retrospective cohort and case-control studies. However, there is a paucity of prospective data and no phase III biomarker studies from North American populations.

METHODS: We conducted a prospective specimen collection, retrospective blinded evaluation (PRoBE) cohort study in patients with cirrhosis enrolled in a 6-monthly surveillance with liver imaging and AFP. Blood samples were prospectively collected every 6 months and analyzed in a retrospective blinded …

Characterizing Mechanism-Based Pain Phenotypes In Patients With Chronic Pancreatitis: A Cross-Sectional Analysis Of The Prospective Evaluation Of Chronic Pancreatitis For Epidemiologic And Translational Studies, Jami L Saloman, Darwin L Conwell, Evan Fogel, Santhi Swaroop Vege, Liang Li, Shuang Li, Dana K Andersen, William E Fisher, Christopher E Forsmark, Phil A Hart, Stephen J Pandol, Walter G Park, Anna Evans Phillips, Mark Topazian, Stephen K Van Den Eeden, Jose Serrano, Dhiraj Yadav

Faculty, Staff and Students Publications

Pain is common in chronic pancreatitis (CP) and profoundly reduces quality of life (QoL). Multiple underlying mechanisms contribute to a heterogenous pain experience and reduce efficacy of pain management. This study was designed to characterize the distribution of mechanism-based pain phenotypes in painful CP. The data analyzed were collected as part of the PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, an NCI/NIDDK-funded longitudinal study of the natural history of CP. The PROspective Evaluation of Chronic pancreatitis for EpidEmiologic and translational stuDies includes patient-reported outcome (PRO) measures of pain, medication use, global health, and QoL. Of subjects (N …

Lnc-Uc147 Is Associated With Disease Stage Of Liver, Gastric, And Renal Cancer, Ana Carolina Rodrigues, Erika Pereira Zambalde, Daniel De Lima Bellan, Edvaldo Da Silva Trindade, Enilze Maria De Souza Fonseca Ribeiro, George Calin, Daniela Fiori Gradia, Jaqueline Carvalho De Oliveira

Faculty, Staff and Student Publications

Lnc-uc.147, a long non-coding RNA derived from a transcribed ultraconserved region (T-UCR), was previously evidenced in breast cancer. However, the role of this region in other tumor types was not previously investigated. The present study aimed to investigate lnc-uc.147 in different types of cancer, as well as to suggest lnc-uc.147 functional and regulation aspects. From solid tumor datasets analysis of The Cancer Genome Atlas (TCGA), deregulated lnc-uc.147 expression was associated with the histologic grade of hepatocellular carcinoma, and with the tumor stage of clear cell renal and gastric adenocarcinoma. Considering the epidemiologic relevance of liver cancer, silencing lnc-uc.147 reduced the …

Monitoring And Modulating Diet And Gut Microbes To Enhance Response And Reduce Toxicity To Cancer Treatment, Anne Knisely, Yongwoo David Seo, Jennifer A Wargo, Manoj Chelvanambi

Faculty, Staff and Student Publications

The gut microbiome comprises a diverse array of microbial species that have been shown to dynamically modulate host immunity both locally and systemically, as well as contribute to tumorigenesis. In this review, we discuss the scientific evidence on the role that gut microbes and diet play in response and toxicity to cancer treatment. We highlight studies across multiple cancer cohorts that have shown an association between particular gut microbiome signatures and an improved response to immune checkpoint blockade, chemotherapy, and adoptive cell therapies, as well as the role of particular microbes in driving treatment-related toxicity and how the microbiome can …