Gastroenterology Commons^™

Gata6-As1 Regulates Intestinal Epithelial Mitochondrial Functions, And Its Reduced Expression Is Linked To Intestinal Inflammation And Less Favourable Disease Course In Ulcerative Colitis, Katya E Sosnovski, Tzipi Braun, Amnon Amir, Danielle Moshel, Marina Benshoshan, Kelli L Vandussen, Nina Levhar, Haya Abbas-Egbariya, Katia Beider, Rakefet Ben-Yishay, Syed Asad Ali, Sean R Moore, Subra Kugathasan, Ifat Abramovich, Efrat Glick Saar, Batya Weiss, Iris Barshack, Eyal Gottlieb, Tamar Geiger, Shomron Ben-Horin, Igor Ulitsky, Jeffrey S Hyams, Lee A Denson, Yael Haberman

Faculty, Staff and Student Publications

BACKGROUND AND AIMS: Widespread dysregulation of long non-coding RNAs [lncRNAs] including a reduction in GATA6-AS1 was noted in inflammatory bowel disease [IBD]. We previously reported a prominent inhibition of epithelial mitochondrial functions in ulcerative colitis [UC]. However, the connection between reduction of GATA6-AS1 expression and attenuated epithelial mitochondrial functions was not defined.

METHODS: Mucosal transcriptomics was used to conform GATA6-AS1 reduction in several treatment-naïve independent human cohorts [n=673]. RNA pull-down followed by mass spectrometry was used to determine the GATA6-AS1 interactome. Metabolomics and mitochondrial respiration following GATA6-AS1 silencing in Caco-2 cells were used to elaborate on GATA6-AS1 functions.

RESULTS: GATA6-AS1 …

Hematopoietic Progenitor Kinase 1 Inhibits The Development And Progression Of Pancreatic Intraepithelial Neoplasia, Hua Wang, Rohan Moniruzzaman, Lei Li, Baoan Ji, Yi Liu, Xiangsheng Zuo, Reza Abbasgholizadeh, Jun Zhao, Guangchao Liu, Ruiqi Wang, Hongli Tang, Ryan Sun, Xiaoping Su, Tse-Hua Tan, Anirban Maitra, Huamin Wang

Faculty, Staff and Student Publications

Ras plays an essential role in the development of acinar-to-ductal metaplasia (ADM) and pancreatic ductal adenocarcinoma (PDAC). However, mutant Kras is an inefficient driver for PDAC development. The mechanisms of the switching from low Ras activity to high Ras activity that are required for development and progression of pancreatic intraepithelial neoplasias (PanINs) are unclear. In this study, we found that hematopoietic progenitor kinase 1 (HPK1) was upregulated during pancreatic injury and ADM. HPK1 interacted with the SH3 domain and phosphorylated Ras GTPase-activating protein (RasGAP) and upregulated RasGAP activity. Using transgenic mouse models of HPK1 or M46, a kinase-dead mutant of …

Antitumor Efficacy Of Dual Blockade With Encorafenib + Cetuximab In Combination With Chemotherapy In Human Brafv600e-Mutant Colorectal Cancer, Stefania Napolitano, Melanie Woods, Hey Min Lee, Vincenzo De Falco, Giulia Martini, Carminia Maria Della Corte, Erika Martinelli, Vincenzo Famiglietti, Davide Ciardiello, Amanda Anderson, Natalie Wall Fowlkes, Oscar Eduardo Villareal, Alexey Sorokin, Preeti Kanikarla, Olu Coker, Van Morris, Lucia Altucci, Josep Tabernero, Teresa Troiani, Fortunato Ciardiello, Scott Kopetz

Faculty, Staff and Student Publications

PURPOSE: Encorafenib + cetuximab (E+C) is an effective therapeutic option in chemorefractory BRAFV600E metastatic colorectal cancer (mCRC). However, there is a need to improve the efficacy of this molecular-targeted therapy and evaluate regimens suitable for untreated BRAFV600E in patients with mCRC.

EXPERIMENTAL DESIGN: We performed a series of in vivo studies using BRAFV600E mCRC tumor xenografts. Mice were randomized to receive 5-fluoruracil (5-FU), irinotecan, or oxaliplatin regimens (FOLFIRI or FOLFOX), (E+C) or the combination. Patients received long-term treatment until disease progression, with deescalation strategies used to mimic maintenance therapy. Transcriptomic changes after progression on cytotoxic chemotherapy or targeted therapy were …

A Novel Endoscopic Ultrasound-Guided Transluminal Anchor Device, Abhishek Agnihotri, Alexander Schlachterman

Division of Gastroenterology and Hepatology Faculty Papers

No abstract provided.

Curated And Harmonized Gut Microbiome 16s Rrna Amplicon Data From Dietary Fiber Intervention Studies In Humans, Cynthia I Rodriguez, Ali Keshavarzian, Bruce R Hamaker, Feitong Liu, Genelle R Lunken, Heather Rasmussen, Hongwei Zhou, Julien Tap, Kelly S Swanson, Maria Ukhanova, Marion Leclerc, Martin Gotteland, Paola Navarrete, Petia Kovatcheva-Datchary, Wendy J Dahl, Jennifer B H Martiny

Faculty, Staff and Student Publications

Next generation amplicon sequencing has created a plethora of data from human microbiomes. The accessibility to this scientific data and its corresponding metadata is important for its reuse, to allow for new discoveries, verification of published results, and serving as path for reproducibility. Dietary fiber consumption has been associated with a variety of health benefits that are thought to be mediated by gut microbiota. To enable direct comparisons of the response of the gut microbiome to fiber, we obtained 16S rRNA sequencing data and its corresponding metadata from 11 fiber intervention studies for a total of 2,368 samples. We provide …

Urinary Cytokines As Potential Biomarkers Of Mild Cognitive Impairment And Alzheimer’S Disease: A Pilot Study, Nazia Saiyed, Ali Yilmaz, Sangeetha Vishweswaraiah, Abhishek Maiti, Ilyas Ustun, Sarah Bartolone, Travonia Brown-Hughes, Roland Thorpe Jr, Tammy Osentoski, Stacey Ruff, Amita Pai, Michael E. Maddens, Khaled Imam, Stewart Graham

Conference Presentation Abstracts

No abstract provided.

Comparative Analyses Define Differences Between Bhd-Associated Renal Tumour And Sporadic Chromophobe Renal Cell Carcinoma, Ryosuke Jikuya, Todd A Johnson, Kazuhiro Maejima, Jisong An, Young-Seok Ju, Hwajin Lee, Kyungsik Ha, Woojeung Song, Youngwook Kim, Yuki Okawa, Shota Sasagawa, Yuki Kanazashi, Masashi Fujita, Seiya Imoto, Taku Mitome, Shinji Ohtake, Go Noguchi, Sachi Kawaura, Yasuhiro Iribe, Kota Aomori, Tomoyuki Tatenuma, Mitsuru Komeya, Hiroki Ito, Yusuke Ito, Kentaro Muraoka, Mitsuko Furuya, Ikuma Kato, Satoshi Fujii, Haruka Hamanoue, Tomohiko Tamura, Masaya Baba, Toshio Suda, Tatsuhiko Kodama, Kazuhide Makiyama, Masahiro Yao, Brian M Shuch, Christopher J Ricketts, Laura S Schmidt, W Marston Linehan, Hidewaki Nakagawa, Hisashi Hasumi

Faculty, Staff and Student Publications

BACKGROUND: Birt-Hogg-Dubé (BHD) syndrome, caused by germline alteration of folliculin (FLCN) gene, develops hybrid oncocytic/chromophobe tumour (HOCT) and chromophobe renal cell carcinoma (ChRCC), whereas sporadic ChRCC does not harbor FLCN alteration. To date, molecular characteristics of these similar histological types of tumours have been incompletely elucidated.

METHODS: To elucidate renal tumourigenesis of BHD-associated renal tumours and sporadic renal tumours, we conducted whole genome sequencing (WGS) and RNA-sequencing (RNA-seq) of sixteen BHD-associated renal tumours from nine unrelated BHD patients, twenty-one sporadic ChRCCs and seven sporadic oncocytomas. We then compared somatic mutation profiles with FLCN variants and RNA expression profiles between BHD-associated …

Pediatric Ercp In The Setting Of Acute Pancreatitis: A Secondary Analysis Of An International Multicenter Cohort Study, Carolena Trocchia, Racha Khalaf, Ernest Amankwah, Wenly Ruan, Douglas S Fishman, Bradley A Barth, Quin Y Liu, Matthew Giefer, Kyung Mo Kim, Mercedes Martinez, Luigi Dall'oglio, Filippo Torroni, Paola De Angelis, Simona Faraci, Sam Bitton, Steven L Werlin, Kulwinder Dua, Roberto Gugig, Clifton Huang, Petar Mamula, J Antonio Quiros, Yuhua Zheng, Travis Piester, Amit Grover, Victor L Fox, Michael Wilsey, David M Troendle

Faculty, Staff and Students Publications

Previous studies have demonstrated the safety of performing endoscopic retrograde cholangiopancreatography (ERCP) in the pediatric population; however, few have addressed the outcomes of children undergoing ERCP during acute pancreatitis (AP). We hypothesize that ERCP performed in the setting of AP can be executed with similar technical success and adverse event profiles to those in pediatric patients without pancreatitis. Using the Pediatric ERCP Database Initiative, a multi-national and multi-institutional prospectively collected dataset, we analyzed 1124 ERCPs. One hundred and ninety-four (17%) of these procedures were performed in the setting of AP. There were no difference in the procedure success rate, procedure …

Rolling Out New Anti-Tuberculosis Drugs Without Diagnostic Capacity, Tara Ness, Le Hong Van, Ilze Petermane, Raquel Duarte, Christoph Lange, Dick Menzies, Daniela Maria Cirillo

Faculty, Staff and Students Publications

Deaths from tuberculosis (TB) reached over 1.6 million in 2021 with 10.6 million people becoming ill. Multidrug-resistant TB, defined as the Mycobacterium tuberculosis organism having resistance to at least isoniazid and rifampicin, represented 3.9% of new TB cases and 18% of previously treated cases. While new drug regimens continue to be developed and introduced to improve treatment of drug-resistant forms of TB, diagnostic capability to identify drug resistance lags woefully behind. While significant mortality benefits exist for these newer drug regimens, implementing them without proper drug resistance diagnostic capacity could lead to development of more drug resistances and exhaust these …

Targets And Study Design For Symptom-Focused Trials Aimed At Patients With Cirrhosis: An Expert Consensus, Arpan A Patel, Elliot B Tapper, Fasiha Kanwal, Christopher D Woodrell, Lissi Hansen, Jennifer C Lai, Shari Rogal, Cara Mcdermott, Mina Rakoski, Nneka N Ufere

Faculty, Staff and Students Publications

BACKGROUND: Symptom-focused trials are critically needed for patients with cirrhosis. However, this work would benefit from standard processes and validated measures.

METHODS: A writing group was formed among hepatologists, nurses, palliative care providers, pharmacists, and clinical trial experts focused on symptom management in patients with cirrhosis to define the key (1) components of trial design, (2) symptom targets, (3) measurement, and (4) outcomes for each target. From July 2022 to January 2023, panelists participated in an iterative process of developing and arriving at a consensus for each component. The goal was to provide consensus definitions that can be operationalized in …

Using Telemedicine To Facilitate Patient Communication And Treatment Decision-Making Following Multidisciplinary Tumor Board Review For Patients With Hepatocellular Carcinoma, Debra T Choi, Yvonne H Sada, Shubhada Sansgiry, David E Kaplan, Tamar H Taddei, Jason K Aguilar, Michael Strayhorn, Ruben Hernaez, Jessica A Davila

Faculty, Staff and Students Publications

BACKGROUND AND AIMS: A rapid increase in the use of telemedicine for delivering healthcare has occurred since the onset of the Covid-19 pandemic. There is evidence for using telemedicine to facilitate cancer care delivery for patients with hepatocellular carcinoma (HCC). Examining how telemedicine can be used to communicate multidisciplinary tumor board (MTB) recommendations for HCC has not been studied. This study has two specific aims: (1) to evaluate the patient perspective of the MTB review process and identify best strategies for communicating treatment recommendations for HCC and (2) to pilot test a telemedicine intervention following MTB review to assess patient …

Stool-Based Tests Mitigate Impacts Of Covid-19 On Colorectal Cancer Screening, Po-Hong Liu, Amit G Singal, Caitlin C Murphy

Faculty, Staff and Student Publications

No abstract provided.

Survival Of Middle Eastern And North African Individuals Diagnosed With Colorectal Cancer: A Population-Based Study In California, Timothy A Zaki, Argyrios Ziogas, Jenny Chang, Caitlin C Murphy, Hoda Anton-Culver

Faculty, Staff and Student Publications

BACKGROUND: Literature on colorectal cancer outcomes in individuals of Middle Eastern and North African (MENA) descent is limited. To address this gap, we estimated five-year colorectal cancer-specific survival by race and ethnicity, including MENA individuals, in a diverse, population-based sample in California.

METHODS: We identified adults (ages 18-79 years) diagnosed with a first or only colorectal cancer in 2004 to 2017 using the California Cancer Registry (CCR), including non-Hispanic White, non-Hispanic Black, non-Hispanic Asian, Hispanic, and MENA individuals. For each racial/ethnic group, we calculated five-year colorectal cancer-specific survival and used Cox proportional hazards regression models to examine the association of …

It Is Better To Light A Candle Than To Curse The Darkness: Single-Cell Transcriptomics Sheds New Light On Pancreas Biology And Disease, Amelia T Cephas, William L Hwang, Anirban Maitra, Oren Parnas, Kathleen E Delgiorno

Faculty, Staff and Student Publications

Recent advances in single-cell RNA sequencing and bioinformatics have drastically increased our ability to interrogate the cellular composition of traditionally difficult to study organs, such as the pancreas. With the advent of these technologies and approaches, the field has grown, in just a few years, from profiling pancreas disease states to identifying molecular mechanisms of therapy resistance in pancreatic ductal adenocarcinoma, a particularly deadly cancer. Single-cell transcriptomics and related spatial approaches have identified previously undescribed epithelial and stromal cell types and states, how these populations change with disease progression, and potential mechanisms of action which will serve as the basis …

Longer Time To Recovery From Acute Kidney Injury Is Associated With Major Adverse Kidney Events In Patients With Cirrhosis, Kavish R Patidar, Mobasshir A Naved, Shaowli Kabir, Ananth Grama, Andrew S Allegretti, Giuseppe Cullaro, Sumeet K Asrani, Astin Worden, Archita P Desai, Marwan S Ghabril, Lauren D Nephew, Eric S Orman

Faculty, Staff and Students Publications

BACKGROUND: In patients with cirrhosis and acute kidney injury (AKI), longer time to AKI-recovery may increase the risk of subsequent major-adverse-kidney-events (MAKE).

AIMS: To examine the association between timing of AKI-recovery and risk of MAKE in patients with cirrhosis.

METHODS: Hospitalised patients with cirrhosis and AKI (n = 5937) in a nationwide database were assessed for time to AKI-recovery and followed for 180-days. Timing of AKI-recovery (return of serum creatinine7-days. Primary outcome was MAKE at 90-180-days. MAKE is an accepted clinical endpoint in AKI and defined as the composite outcome of ≥25% decline in estimated-glomerular-filtration-rate (eGFR) compared with baseline with …

Patient-Reported Bowel Function And Bowel-Related Quality Of Life After Pelvic Radiation For Rectal Adenocarcinoma: The Impact Of Radiation Fractionation And Surgical Resection, Michael K Rooney, Brian De, Kelsey Corrigan, Grace L Smith, Cullen Taniguchi, Bruce D Minsky, Ethan B Ludmir, Eugene J Koay, Prajnan Das, Albert C Koong, Oliver Peacock, George Chang, Y Nancy You, Van K Morris, Graciela Nogueras-González, Emma B Holliday

Faculty, Staff and Student Publications

INTRODUCTION: Multimodality treatment for locally advanced rectal cancer (LARC) can include long-course radiotherapy (LCRT) or short course radiotherapy (SCRT). Nonoperative management is increasingly pursued for those achieving a complete clinical response. Data regarding long-term function and quality-of-life (QOL) are limited.

METHODS: Patients with LARC treated with radiotherapy from 2016 to 2020 completed the Functional Assessment of Cancer Therapy- General (FACT-G7), the Low Anterior Resection Syndrome Score (LARS) and the Fecal Incontinence QOL Scale (FIQOL). Univariate and multivariable linear regression analyses identified associations between clinical variables including radiation fractionation and the use of surgery versus non-operative management.

RESULTS: Of 204 patients …

Clinical Spectrum And Genetic Causes Of Mitochondrial Hepatopathy Phenotype In Children, James E Squires, Alexander G Miethke, C Alexander Valencia, Kieran Hawthorne, Lisa Henn, Johan L K Van Hove, Robert H Squires, Kevin Bove, Simon Horslen, Rohit Kohli, Jean P Molleston, Rene Romero, Estella M Alonso, Jorge A Bezerra, Stephen L Guthery, Evelyn Hsu, Saul J Karpen, Kathleen M Loomes, Vicky L Ng, Philip Rosenthal, Krupa Mysore, Kasper S Wang, Marisa W Friederich, John C Magee, Ronald J Sokol, Childhood Liver Disease Research Network (Children)

Faculty, Staff and Students Publications

BACKGROUND: Alterations in both mitochondrial DNA (mtDNA) and nuclear DNA genes affect mitochondria function, causing a range of liver-based conditions termed mitochondrial hepatopathies (MH), which are subcategorized as mtDNA depletion, RNA translation, mtDNA deletion, and enzymatic disorders. We aim to enhance the understanding of pathogenesis and natural history of MH.

METHODS: We analyzed data from patients with MH phenotypes to identify genetic causes, characterize the spectrum of clinical presentation, and determine outcomes.

RESULTS: Three enrollment phenotypes, that is, acute liver failure (ALF, n = 37), chronic liver disease (Chronic, n = 40), and post-liver transplant (n = 9), were analyzed. …

Probiotics And Human Milk Differentially Influence The Gut Microbiome And Nec Incidence In Preterm Pigs, Valeria Melendez Hebib, Diana H Taft, Barbara Stoll, Jinxin Liu, Lee Call, Gregory Guthrie, Nick Jensen, Amy B Hair, David A Mills, Douglas G Burrin

Faculty, Staff and Students Publications

Necrotizing enterocolitis (NEC) is the leading cause of death caused by gastrointestinal disease in preterm infants. Major risk factors include prematurity, formula feeding, and gut microbial colonization. Microbes have been linked to NEC, yet there is no evidence of causal species, and select probiotics have been shown to reduce NEC incidence in infants. In this study, we evaluated the effect of the probiotic Bifidobacterium longum subsp. infantis (BL. infantis), alone and in combination with a human milk oligosaccharide (HMO)—sialylactose (3′SL)—on the microbiome, and the incidence of NEC in preterm piglets fed an infant formula diet. We studied 50 …

Cachexia, Chorea, And Pain In Chronic Nonbacterial Osteitis And Inflammatory Bowel Disease: A Case Report, Ladan Agharokh, Katherine Mamola, Andrew G Yu, Annette L Medina, Bhaskar Gurram, Julie Fuller, Jason Y Park, Weina Chen, Veena Rajaram, Matthew R Hammer, Jeff L Waugh

Faculty, Staff and Student Publications

BACKGROUND: Inflammatory bowel disease is an inflammatory disorder that primarily impacts the gastrointestinal tract, leading to malnutrition and chronic microscopic intestinal blood loss. Uncontrolled systemic inflammation can impact other parts of the body, known as extraintestinal manifestations. Up to 25% of patients with inflammatory bowel disease are reported to have these complications in their skin, joints, bones, eyes, liver, lung, and pancreas (Rogler et al. in Gastroenterology 161(4):1118-1132, 2021). Neurologic involvement as extraintestinal manifestations are less common, reported at 3-19%, including neuropathies, demyelination, and cerebrovascular events (Morís in World J Gastroenterol. 20(5):1228-1237, 2014).

CASE PRESENTATION: A 13-year-old Caucasian boy presented …

Safety And Indications For Endoscopic Retrograde Cholangiopancreatography In Liver Transplant Patients: An Analysis Of The United States’ National Inpatient Sample Database, Zahid Ijaz Tarar, Umer Farooq, Mustafa Gandhi, Muhammad Usman Zafar, Saad Saleem, Faisal Kamal

Division of Gastroenterology and Hepatology Faculty Papers

BACKGROUND: Endoscopic retrograde cholangiopancreatography (ERCP) is performed to treat biliary complications after a liver transplantation; however, the previously available literature on the safety of ERCP in liver transplant patients is limited. We aimed to study the safety of ERCP in liver transplant patients.

METHODS: We used a National Inpatient Sample database from 2016-2019 to identify patients who underwent ERCP and had a history of a liver transplantation, using the international classification of diseases, 10

RESULTS: Liver transplant patients who underwent ERCP had a higher rate of post-ERCP pancreatitis and bleeding compared to the general adult population (11.39% vs. 9.19%, 0.83% …