Medicine and Health Sciences Commons^™

Immune-Mediated Colitis From Dual Checkpoint Inhibitors., Nishanth Thalambedu, Yasir Khan, Qian Zhang, Shristi Khanal, Ammar Ashfaq

Abington Jefferson Health Papers

Melanoma is a deadly disease with immunotherapy treatment options that emerged in the last few years and have changed the disease outcome. However, it is associated with immune-related toxic effects despite improving survival. We present the case of a 53-year-old woman who had two weeks of diarrhea after she was treated with dual immunotherapy agents for her advanced melanoma. The final workup revealed pancolitis, possibly due to immunotherapy adverse effects. Initial conservative treatment, unfortunately, did not lead to a clinical improvement until a steroid was introduced. We are reporting this case to alert our fellow physicians about the immune-mediated toxicities …

Role Of Probiotics In Non-Alcoholic Fatty Liver Disease: Does Gut Microbiota Matter?, Chencheng Xie, Dina Halegoua-De Marzio

Division of Gastroenterology and Hepatology Faculty Papers

Non-alcoholic fatty liver disease (NAFLD) is the hepatic consequence of metabolic syndrome, which often also includes obesity, diabetes, and dyslipidemia. The connection between gut microbiota (GM) and NAFLD has attracted significant attention in recent years. Data has shown that GM affects hepatic lipid metabolism and influences the balance between pro/anti-inflammatory effectors in the liver. Although studies reveal the association between GM dysbiosis and NAFLD, decoding the mechanisms of gut dysbiosis resulting in NAFLD remains challenging. The potential pathophysiology that links GM dysbiosis to NAFLD can be summarized as: (1) disrupting the balance between energy harvest and expenditure, (2) promoting hepatic …

Silymarin In Non-Cirrhotics With Non-Alcoholic Steatohepatitis: A Randomized, Double-Blind, Placebo Controlled Trial., Victor J. Navarro, Steven H. Belle, Massimo D'Amato, Nezam Adfhal, Elizabeth M. Brunt, Michael W. Fried, K. Rajender Reddy, Abdus S. Wahed, Stephen Harrison

Division of Gastroenterology and Hepatology Faculty Papers

The botanical product silymarin, an extract of milk thistle, is commonly used by patients to treat chronic liver disease and may be a treatment for NASH due to its antioxidant properties. We aimed to assess the safety and efficacy of higher than customary doses of silymarin in non-cirrhotic patients with NASH. This exploratory randomized double-blind placebo controlled multicenter Phase II trial tested a proprietary standardized silymarin preparation (Legalon®, Rottapharm|Madaus, Mylan) and was conducted at 5 medical centers in the United States. Eligible adult patients had liver biopsy within 12 months showing NASH without cirrhosis with NAFLD Activity Score (NAS) ≥4 …

Excision Repair Cross-Complementing Group-1 (Ercc1) Induction Kinetics And Polymorphism Are Markers Of Inferior Outcome In Patients With Colorectal Cancer Treated With Oxaliplatin., Devika Rao, Atrayee Basu Mallick, Titto Augustine, Cecilia Daroqui, Jeeshan Jiffry, Amartej Merla, Imran Chaudhary, Raviraja Seetharam, Arjun Sood, Srikanth Gajavelli, Santiago Aparo, Lakshmi Rajdev, Andreas Kaubisch, Jennifer Chuy, Abdissa Negassa, John M. Mariadason, Radhashree Maitra, Sanjay Goel

Department of Medical Oncology Faculty Papers

Background: ERCC1, a component of nucleotide excision repair pathway, is known to repair DNA breaks induced by platinum drugs. We sought to ascertain if ERCC1 expression dynamics and a single nucleotide polymorphism (SNP) rs11615 are biomarkers of sensitivity to oxaliplatin therapy in patients with colorectal cancer (CRC).

Methods: Western blot and qPCR for ERCC1 expression was performed from PBMCs isolated from patients receiving oxaliplatin-based therapy at specified timepoints. DNA was also isolated from 59 biorepository specimens for SNP analysis. Clinical benefit was determined using progression free survival (PFS) for metastatic CRC.

Results: ERCC1 was induced in PBMC in response to …

Optimal Timing And Route Of Nutritional Support After Esophagectomy: A Review Of The Literature., Richard Zheng, Courtney L. Devin, Michael J. Pucci, Adam C. Berger, Ernest L. Rosato, Francesco Palazzo

Department of Surgery Faculty Papers

Some controversy surrounds the postoperative feeding regimen utilized in patients who undergo esophagectomy. Variation in practices during the perioperative period exists including the type of nutrition started, the delivery route, and its timing. Adequate nutrition is essential for this patient population as these patients often present with weight loss and have altered eating patterns after surgery, which can affect their ability to regain or maintain weight. Methods of feeding after an esophagectomy include total parenteral nutrition, nasoduodenal/nasojejunal tube feeding, jejunostomy tube feeding, and oral feeding. Recent evidence suggests that early oral feeding is associated with shorter LOS, faster return of …

Appropriate Therapeutic Drug Monitoring Of Biologic Agents For Patients With Inflammatory Bowel Diseases., Konstantinos Papamichael, Adam S. Cheifetz, Gil Y. Melmed, Peter M. Irving, Niels Vande Casteele, Patricia L. Kozuch, Laura E. Raffals, Leonard Baidoo, Brian Bressler, Shane M. Devlin, Jennifer Jones, Gilaad G. Kaplan, Miles P. Sparrow, Fernando S Velayos, Thomas Ullman, Corey A. Siegel

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND & AIMS: Therapeutic drug monitoring (TDM) is widely available for biologic therapies in patients with inflammatory bowel disease (IBD). We reviewed current data and provided expert opinion regarding the clinical utility of TDM for biologic therapies in IBD.

METHODS: We used a modified Delphi method to establish consensus. A comprehensive literature review was performed regarding the use of TDM of biologic therapy in IBD and presented to international IBD specialists. Subsequently, 28 statements on the application of TDM in clinical practice were rated on a scale of 1 to 10 (1 = strongly disagree and 10 = strongly agree) …

Blunted Evoked Prouroguanylin Endocrine Secretion In Chronic Constipation., Scott A. Waldman, Renata Tenenbaum, Henry C. Foehl, Peter Winkle, Patrick Griffin

Department of Pharmacology and Experimental Therapeutics Faculty Papers

OBJECTIVES: Prouroguanylin (ProUGN) in the intestine is cleaved to form uroguanylin (UGN), which stimulates guanylate cyclase C (GUCY2C), inducing cyclic guanosine monophosphate signaling. Paracrine release regulates fluid secretion, contributing to bowel function, whereas endocrine secretion evoked by eating forms a gut-brain axis, controlling appetite. Whereas hormone insufficiency contributes to hyperphagia in obesity, its contribution to the pathophysiology of constipation syndromes remains unexplored. Here, we compared circulating ProUGN and UGN in healthy subjects and in patients with chronic idiopathic constipation (CIC) and patients with irritable bowel syndrome with constipation (IBS-C).

METHODS: Circulating ProUGN and UGN levels were measured in 60 healthy …

Whole Genome Metagenomic Analysis Of The Gut Microbiome Of Differently Fed Infants Identifies Differences In Microbial Composition And Functional Genes, Including An Absent Crispr/Cas9 Gene In The Formula-Fed Cohort, Matthew D. Di Guglielmo, Karl Franke, Courtney Cox, Erin L. Crowgey

Department of Pediatrics Faculty Papers

Background: Advancements in sequencing capabilities have enhanced the study of the human microbiome. There are limited studies focused on the gastro-intestinal (gut) microbiome of infants, particularly the impact of diet between breast-fed (BF) versus formula-fed (FF). It is unclear what effect, if any, early feeding has on short- term or long-term composition and function of the gut microbiome.

Results: Using a shotgun metagenomics approach, differences in the gut microbiome between BF (n = 10) and FF (n = 5) infants were detected. A Jaccard distance principle coordinate analysis was able to cluster BF versus FF infants based on the presence …

Discontinuation Of Proton Pump Inhibitor Use Reduces The Number Of Endoscopic Procedures Required For Resolution Of Walled-Off Pancreatic Necrosis., Patrick C. Powers, Ali Siddiqui, Reem Z. Sharaiha, Grace Yang, Enad Dawod, Aleksey A. Novikov, Amy Javia, Cynthia Edirisuriya, Arish Noor, Tayebah Mumtaz, Usama Iqbal, David .E Loren, Thomas E. Kowalski, Natalie Cosgrove, Yordano Alicea, Amy Tyberg, Iman Andalib, Michel Kahaleh, Douglas G. Adler

Division of Gastroenterology and Hepatology Faculty Papers

Background and Objectives: Endoscopic drainage/debridement of symptomatic walled off necrosis (WON) using lumen-apposing metal stents (LAMS) is both safe and effective. While endoscopic management of WON is the standard approach to treatment, the ideal concomitant medical therapy remains unclear. The purpose of this study was to further elucidate the effect of proton pump inhibitor (PPIs) therapy on the technical and clinical success of endoscopic treatment of WON.

Methods: Two hundred and seventy-two patients in 8 centers with WON managed by endoscopic drainage using LAMS were evaluated. Patients were followed for at least 6 months following treatment. The patients were divided …

Downregulation Of Thromboxane A2 And Angiotensin Ii Type 1 Receptors Associated With Aging-Related Decrease In Internal Anal Sphincter Tone., Ipsita Mohanty, Jagmohan Singh, Satish Rattan

Division of Gastroenterology and Hepatology Faculty Papers

Aging-associated decrease in internal anal sphincter (IAS) tone (AADI) is a major contributor in the rectoanal incontinence (RI). To determine the pathogenesis of AADI, we investigated the effect of aging on GPCR activation and related downstream signaling. We particularly investigated two GPCRs that characterize IAS smooth muscle cells (SMCs): thromboxane A ₂ and angiotensin II type 1. Two groups of Fischer 344 rats (6-month-old [young group] and 26-month-old [old group]) were employed to determine the GPCR function by isometric contraction, the expressions of GPCRs, and their downstream regulatory signaling proteins (regulator of G-protein signaling 2, RGS2; GPCR Kinase 5, GRK5; …

The Time Is Now For Mandatory Liver-Focused Clinical Experiences In Medical School., Alexander Y. Pan, Lauren D. Feld, Jeanne M. Farnan, Steven K. Herrine, Adam E. Mikolajczyk

Division of Gastroenterology and Hepatology Faculty Papers

The national burden of chronic liver disease is steadily increasing and is only expected to worsen with the ongoing obesity and opioid epidemics fueling growth in the prevalence of nonalcoholic fatty liver disease and a resurgence of new hepatitis C infections. Our letter highlights the disparity between the rising prevalence of chronic liver disease and the proportion of medical students who receive exposure to patients with liver disease as part of their medical education. A more comprehensive survey of clerkship directors is needed to further corroborate this data, which may lead to reforms in medical school curricula to better address …

A Rare Case Of Wilson Disease In A 72-Year-Old Patient., Christopher Cao, Timothy Colangelo, Raja Koteswar Dhanekula, Daniel Brandt, Indira Laothamatas, Manish Thapar, Steven K. Herrine, Jesse M. Civan

Division of Gastroenterology and Hepatology Faculty Papers

Wilson disease is an autosomal recessive disorder of abnormal copper metabolism that is prevalent in the younger population, rarely presenting in patients older than 40 years. Clinical presentation may be variable, and diagnosis is often aided by clinical and biochemical tests. We report the case of a 72-year-old woman who presented with acute liver failure initially of unclear etiology. Our patient was initially managed for presumed drug-induced liver injury but ultimately diagnosed with Wilson disease on the basis of clinical presentation, laboratory testing, liver biopsy, quantitative hepatic copper, and abnormal genetic testing.

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 = …

Persistent Risk For New, Subsequent New And Recurrent Hepatocellular Carcinoma Despite Successful Anti-Hepatitis B Virus Therapy And Tumor Ablation: The Need For Hepatitis B Virus Cure., Brianna J. Shinn, Aaron Martin, Robert M. Coben, Mitchell I. Conn, Jorge Prieto, Howard Kroop, Anthony J. Dimarino, Hie-Won Hann

Division of Gastroenterology and Hepatology Faculty Papers

Hepatitis B virus (HBV) is one of the most significant hepatocarcinogens. The ultimate goal of anti-HBV treatment is to prevent the development of hepatocellular carcinoma (HCC). During the last two decades, with the use of currently available anti-HBV therapies (lamivudine, entecavir and tenofovir disoproxil fumatate), there has been a decrease in the incidence of HBV-associated HCC (HBV-HCC). Furthermore, several studies have demonstrated a reduction in recurrent or new HCC development after initial HCC tumor ablation. However, during an observation period spanning 10 to 20 years, several case reports have demonstrated the development of new, subsequent new and recurrent HCC even …