Gastroenterology Commons^™

Neonatal Graves' Disease With Maternal Hypothyroidism., Gangaram Akangire, Alain Cuna, Charisse I. Lachica, Ryan T. Fischer, Sripriya Raman, Venkatesh Sampath

Manuscripts, Articles, Book Chapters and Other Papers

Neonatal Graves' disease presenting as conjugated hyperbilirubinemia is a diagnostic challenge because the differential includes a gamut of liver and systemic diseases. We present a unique case of neonatal Graves' disease in a premature infant with conjugated hyperbilirubinemia born to a mother with hypothyroidism during pregnancy and remote history of Graves' disease. Infant was treated with a combination of methimazole, propranolol, and potassium iodide for 4 weeks. Thyroid function improved after 8 weeks of treatment with full recovery of thyroid function, disappearance of thyroid-stimulating antibodies, and resolution of failure to thrive and conjugated hyperbilirubinemia. This case provides several clinical vignettes …

Endoscopic Resolution And Recurrence Of Gastric Antral Vascular Ectasia After Serial Treatment With Argon Plasma Coagulation, Shashank Garg, Bilal Aslam, Nicholas Nickl

Internal Medicine Faculty Publications

AIM

To evaluate long-term endoscopic resolution and recurrence rate of gastric antral vascular ectasia (GAVE) after argon plasma coagulation (APC) treatment.

METHODS

This was an IRB-approved retrospective single center study that included patients endoscopically treated for GAVE between 1/1/2008 to 12/31/2014. The primary and secondary end points of the study were rate of endoscopic resolution of GAVE after APC treatment and recurrence rate of GAVE after endoscopic resolution, respectively. Endoscopic resolution of GAVE was defined as no endoscopic evidence of GAVE after treatment with APC. Recurrence of GAVE was defined as endoscopic reappearance of GAVE after prior resolution.

RESULTS

Twenty …

Bioactivity Of Oral Linaclotide In Human Colorectum For Cancer Chemoprevention., David S. Weinberg, Jieru E. Lin, Nathan R. Foster, Gary Della'zanna, Asad Umar, Drew Seisler, Walter K. Kraft, David M. Kastenberg, Leo C. Katz, Paul J. Limburg, Scott A. Waldman

Department of Pharmacology and Experimental Therapeutics Faculty Papers

Guanylate cyclase C (GUCY2C) is a tumor-suppressing receptor silenced by loss of expression of its luminocrine hormones guanylin and uroguanylin early in colorectal carcinogenesis. This observation suggests oral replacement with a GUCY2C agonist may be an effective targeted chemoprevention agent. Linaclotide is an FDA-approved oral GUCY2C agonist formulated for gastric release, inducing fluid secretion into the small bowel to treat chronic idiopathic constipation. The ability of oral linaclotide to induce a pharmacodynamic response in epithelial cells of the colorectum in humans remains undefined. Here, we demonstrate that administration of 0.87 mg of oral linaclotide daily for 7 days to healthy …

Response To Comment On Ahsan Ali Syed Et Al (J Pak Med Assoc 2017; 67: 400-404 Frequency Of Worsening Liver Function In Severe Dengue Hepatitis Patients Receiving Paracetamol: A Retrospective Analysis Of Hospital Data, Syed Ahsan Ali

Section of Gastroenterology

No abstract provided.

How An Alloreactive T-Cell Receptor Achieves Peptide And Mhc Specificity, Yuan Wang, Nishant K. Singh, Timothy T. Spear, Lance M. Hellman, Kurt H. Piepenbrink, Rachel H. Mcmahan, Hugo R. Rosen, Craig W. Vander Kooi, Michael I. Nishimura, Brian M. Baker

Food for Health: Publications

T-cell receptor (TCR) allorecognition is often presumed to be relatively nonspecific, attributable to either a TCR focus on exposed major histocompatibility complex (MHC) polymorphisms or the degenerate recognition of allopeptides. However, paradoxically, alloreactivity can proceed with high peptide and MHC specificity. Although the underlying mechanisms remain unclear, the existence of highly specific alloreactive TCRs has led to their use as immunotherapeutics that can circumvent central tolerance and limit graft-versus-host disease. Here, we show how an alloreactive TCR achieves peptide and MHC specificity. The HCV1406 TCR was cloned from T cells that expanded when a hepatitis C virus (HCV)-infected HLA-A2− individual …

Role Of Differentially Expressed Microrna-139-5p In The Regulation Of Phenotypic Internal Anal Sphincter Smooth Muscle Tone., Jagmohan Singh, Ipsita Mohanty, Sankar Addya, Benjamin Philllips, Hwan Mee Yong, Steven S. An, Raymond B. Penn, Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

The present study focused on the role of microRNA-139-5p (miRNA-139-5p) in the regulation of basal tone in internal anal sphincter (IAS). Applying genome-wide miRNA microarrays on the phenotypically distinct smooth muscle cells (SMCs) within the rat anorectrum, we identified miRNA-139-5p as differentially expressed RNA repressor with highest expression in the purely phasic smooth muscle of anococcygeus (ASM) vs. the truly tonic smooth muscle of IAS. This pattern of miRNA-139-5p expression, previously shown to target ROCK2, was validated by target prediction using ingenuity pathway (IPA) and by qPCR analyses. Immunoblotting, immunocytochemistry (ICC), and functional assays using IAS tissues and cells subjected …

Decreasing Cost In The Gi Endoscopy Suite By Utilizing Best Sedation Practices, Casey Brianne Mancini

Doctoral Projects

Colorectal cancer is a leading cause of cancer death in the United States (Mandel, Tanner, Lichtenstein, Metz, Katzka, Ginsberg, & Kochman, 2008; Siegel, DeSantis, & Jemal, 2014). Because this lethal disease claims lives of many people every year, more patients are undergoing screening colonoscopies, which have greatly aided in decreasing the number of colorectal cancer deaths (Siegel et al., 2014). The most common form of sedation for colonoscopies is moderate sedation with a benzodiazepine and an opioid (Cohen, Hightower, Wood, Miller, & Aisenberg, 2004; Lera dos Santos, et. al., 2013). However, sedation by anesthesia providers using propofol is becoming more …

Interdependency Of Egf And Glp-2 Signaling In Attenuating Mucosal Atrophy In A Mouse Model Of Parenteral Nutrition, Yongjia Feng, Farok R. Demehri, Weidong Xiao, Yu-Hwai Tsai, Jennifer C. Jones, Constance D. Brindley, David W. Threadgill, Jens J. Holst, Bolette Hartmann, Terrence A. Barrett, Daniel H. Teitelbaum, Peter J. Dempsey

Internal Medicine Faculty Publications

BACKGROUND & AIMS: Total parenteral nutrition (TPN), a crucial treatment for patients who cannot receive enteral nutrition, is associated with mucosal atrophy, barrier dysfunction, and infectious complications. Glucagon-like peptide-2 (GLP-2) and epidermal growth factor (EGF) improve intestinal epithelial cell (IEC) responses and attenuate mucosal atrophy in several TPN models. However, it remains unclear whether these 2 factors use distinct or overlapping signaling pathways to improve IEC responses. We investigated the interaction of GLP-2 and EGF signaling in a mouse TPN model and in patients deprived of enteral nutrition.

METHODS: Adult C57BL/6J, IEC-Egfr^{knock out (KO)} and IEC-pik3r1^KO mice receiving …

Nobody Really Knows How To Perform Endoscopic Necrosectomy., Douglas G. Adler, Ali A. Siddiqui

Division of Gastroenterology and Hepatology Faculty Papers

No abstract provided.

Clinical Characteristics And Outcome Of Budd-Chiari Syndrome At A Tertiary Care Hospital In Pakistan., Om Parkash, Aysha Khan, Saeed Hamid

Section of Gastroenterology

OBJECTIVE: To determine the clinical characteristics of Budd-Chiari syndrome (BCS), its causes and outcome at a tertiary care hospital.

STUDY DESIGN: An observational study

.PLACE AND DURATION OF STUDY: The Aga Khan University Hospital,Karachi, from 2004 to 2014.

METHODOLOGY: Aretrospective analysis of data was conducted. Apredesigned questionnaire was filled from medical records of patients with BCS. Clinical features, etiology, management and outcome was noted from 2004 to 2014. Descriptive statistics were determined.

RESULTS: Forty-five patients' charts were reviewed; 26 (57.8%) were male patients. The median (IQR) age at diagnosis was 26.0 (20.5 to 34.5) years. Primary BCS was seen in …

Exome Analysis Of Rare And Common Variants Within The Nod Signaling Pathway., Gaia Andreoletti, Valentina Shakhnovich, Kathy Christenson, Tracy Coelho, Rachel Haggarty, Nadeem A. Afzal, Akshay Batra, Britt-Sabina Petersen, Matthew Mort, R Mark Beattie, Sarah Ennis

Manuscripts, Articles, Book Chapters and Other Papers

Pediatric inflammatory bowel disease (pIBD) is a chronic heterogeneous disorder. This study looks at the burden of common and rare coding mutations within 41 genes comprising the NOD signaling pathway in pIBD patients. 136 pIBD and 106 control samples underwent whole-exome sequencing. We compared the burden of common, rare and private mutation between these two groups using the SKAT-O test. An independent replication cohort of 33 cases and 111 controls was used to validate significant findings. We observed variation in 40 of 41 genes comprising the NOD signaling pathway. Four genes were significantly associated with disease in the discovery cohort …

Novel Genetic Variants Associated With Child Refractory Esophageal Stricture With Food Allergy By Exome Sequencing., Min Yang, Min Xiong, Huan Chen, Lanlan Geng, Peiyu Chen, Jing Xie, Shui Qing Ye, Ding-You Li, Sitang Gong

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Refractory esophageal stricture (RES) may be attributed to food allergy. Its etiology and pathogenesis are not fully understood. Identification of novel genetic variants associated with this disease by exome sequencing (exome-seq) may provide new mechanistic insights and new therapeutic targets.

METHODS: To identify new and novel disease-associating variants, whole-exome sequencing was performed on an Illumina NGS platform in three children with RES as well as food allergy.

RESULTS: A total of 91,024 variants were identified. By filtering out 'normal variants' against those of the 1000 Genomes Project, we identified 12,741 remaining variants which are potentially associated with RES plus …

Gastrointestinal Stromal Tumor Induced Hypercalcemia, Aram Barbaryan, Stefania Bailuc, Padma Poddutoori, Aida Richardson, Aibek E. Mirrakhimov

Internal Medicine Faculty Publications

Hypercalcemia in patients with cancer is a common laboratory finding affecting up to 44% of that patient population. 1,25-Dihydroxyvitamin D₃ mediated hypercalcemia is one of the rare mechanisms of this endocrine emergency in cancer patients. It is even rarer for solid organ neoplasms to present with hypercalcemia mediated through the production of 1,25-dihydroxyvitamin D₃. We report a case of a 77-year-old female who presented to the hospital with hypercalcemia and later was found to have metastatic gastrointestinal stromal tumor. There have been only 5 cases of gastrointestinal stromal tumor described in literature resulting in hypercalcemia. In our …

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.

Causal Pathways From Enteropathogens To Environmental Enteropathy: Findings From The Mal-Ed Birth Cohort Study, Margaret N. Kosek, Zulfiqar Ahmed Bhutta, Anita K. M. Zaidi, Imran Ahmed, Syed Asad Ali, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Didar Alam, Shahida Qureshi

Department of Paediatrics and Child Health

Background: Environmental enteropathy (EE), the adverse impact of frequent and numerous enteric infections on the gut resulting in a state of persistent immune activation and altered permeability, has been proposed as a key determinant of growth failure in children in low- and middle-income populations. A theory-driven systems model to critically evaluate pathways through which enteropathogens, gut permeability, and intestinal and systemic inflammation affect child growth was conducted within the framework of the Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) birth cohort study that included children from eight countries. …

Review Article: Pathogenesis And Clinical Manifestations Of Gastrointestinal Involvement In Systemic Sclerosis., Sumit Kumar, Jagmohan Singh, Satish Rattan, Anthony J. Dimarino, Sidney Cohen, Sergio A. Jimenez

Department of Dermatology and Cutaneous Biology Faculty Papers

BACKGROUND: Gastrointestinal tract (GIT) involvement is a common cause of debilitating symptoms in patients with systemic sclerosis (SSc). There are no disease modifying therapies for this condition and the treatment remains symptomatic, largely owing to the lack of a clear understanding of its pathogenesis.

AIMS: To investigate novel aspects of the pathogenesis of gastrointestinal involvement in SSc. To summarise existing knowledge regarding the cardinal clinical gastrointestinal manifestations of SSc and its pathogenesis, emphasising recent investigations that may be valuable in identifying potentially novel therapeutic targets.

METHODS: Electronic (PubMed/Medline) and manual Google search.

RESULTS: The GIT is the most common internal …

Clostridium Septicum Aortitis With Synchronous Ascending Colon And Rectal Adenocarcinoma., Deepanshu Jain, Andrew C. Kistler, Patricia L. Kozuch

Division of Gastroenterology and Hepatology Faculty Papers

Clostridium septicum (C. septicum) aortitis is a rare condition frequently associated with colon adenocarcinoma and carries a poor prognosis. We report the case of a 66-year-old man who presented with abdominal pain, blood in the stool, fever and chills. Laboratory tests were significant for leukocytosis and microcytic anemia. Abdominal imaging revealed a right colon mass and aortitis. Colonoscopy confirmed the right colon mass and also discovered a rectal mass, both adenocarcinomas. Treatment consisted of antibiotics, aortic repair, right hemi-colectomy and later trans-anal excision of the rectal mass. Blood cultures and the aortic specimen grew C. septicum. The patient improved and …

Polyp Resection - Controversial Practices And Unanswered Questions, Daniel Von Renteln, Heiko Pohl

Dartmouth Scholarship

Detection and complete removal of precancerous neoplastic polyps are central to effective colorectal cancer screening. The prevalence of neoplastic polyps in the screening population in the United States is likely 450%. However, most persons with neoplastic polyps are never destined to develop cancer, and do not benefit for finding and removing polyps, and may only be harmed by the procedure. Further 70–80% of polyps are diminutive (≤5 mm) and such polyps almost never contain cancer. Given the questionable benefit, the high-cost and the potential risk changing our approach to the management of diminutive polyps is currently debated. Deemphasizing diminutive polyps …

Mortality Associated With Gastrointestinal Bleeding In Children: A Retrospective Cohort Study., Thomas M. Attard, Mikaela Miller, Chaitanya Pant, Ashwath Kumar, Mike Thomson

Manuscripts, Articles, Book Chapters and Other Papers

AIM: To determine the clinical characteristics of children with gastrointestinal bleeding (GIB) who died during the course of their admission.

METHODS: We interrogated the Pediatric Hospital Information System database, including International Classification of Diseases, Current Procedural Terminology and Clinical Transaction Classification coding from 47 pediatric tertiary centers extracting the population of patients (1-21 years of age) admitted (inpatient or observation) with acute, upper or indeterminate GIB (1/2007-9/2015). Descriptive statistics, unadjusted univariate and adjusted multivariate analysis of the associations between patient characteristics and treatment course with mortality was performed with mortality as primary and endoscopy a secondary outcome of interest. All …

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 …