Gastroenterology Commons^™

Genomic Characterization Of Malignant Progression In Neoplastic Pancreatic Cysts, Michaël Noë, Noushin Niknafs, Catherine G Fischer, Wenzel M Hackeng, Violeta Beleva Guthrie, Waki Hosoda, Marija Debeljak, Eniko Papp, Vilmos Adleff, James R White, Claudio Luchini, Antonio Pea, Aldo Scarpa, Giovanni Butturini, Giuseppe Zamboni, Paola Castelli, Seung-Mo Hong, Shinichi Yachida, Nobuyoshi Hiraoka, Anthony J Gill, Jaswinder S Samra, G Johan A Offerhaus, Anne Hoorens, Joanne Verheij, Casper Jansen, N Volkan Adsay, Wei Jiang, Jordan Winter, Jorge Albores-Saavedra, Benoit Terris, Elizabeth D Thompson, Nicholas J Roberts, Ralph H Hruban, Rachel Karchin, Robert B Scharpf, Lodewijk A A Brosens, Victor E Velculescu, Laura D Wood

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Intraductal papillary mucinous neoplasms (IPMNs) and mucinous cystic neoplasms (MCNs) are non-invasive neoplasms that are often observed in association with invasive pancreatic cancers, but their origins and evolutionary relationships are poorly understood. In this study, we analyze 148 samples from IPMNs, MCNs, and small associated invasive carcinomas from 18 patients using whole exome or targeted sequencing. Using evolutionary analyses, we establish that both IPMNs and MCNs are direct precursors to pancreatic cancer. Mutations in SMAD4 and TGFBR2 are frequently restricted to invasive carcinoma, while RNF43 alterations are largely in non-invasive lesions. Genomic analyses suggest an average window of over three …

Neuroendocrine Tumor Of The Gallbladder, A Rare Incidental Finding, Alvaro Frometa, Yasna Chaudhary, Omar Ansari, Nigel Jagoo, Iqbal Kapadia

HCA Healthcare Journal of Medicine

Background: Neuroendocrine tumors are a rare finding in the gallbladder. The incidence of this entity in the gallbladder is roughly 1.13 cases per 100,000 in the US, with a steady increase in the last decade. Gallbladder neuroendocrine tumors are generally asymptomatic; the majority of cases have been reported as incidental findings in specimens, resected due to secondary symptomatology, such as chronic cholecystitis. Treatment strategies are limited, in part due to the often advanced stage in which this disease presents. Furthermore, there is a restricted utility of diagnostic tools for early detection; these factors contribute to the poor prognosis of this …

Spermine Synthase And Myc Cooperate To Maintain Colorectal Cancer Cell Survival By Repressing Bim Expression, Yubin Guo, Qing Ye, Pan Deng, Yanan Cao, Daheng He, Zhaohe Zhou, Chi Wang, Yekaterina Y. Zaytseva, Charles E. Schwartz, Eun Young Lee, B. Mark Evers, Andrew J. Morris, Side Liu, Qing-Bai She

Markey Cancer Center Faculty Publications

Dysregulation of polyamine metabolism has been linked to the development of colorectal cancer (CRC), but the underlying mechanism is incompletely characterized. Here, we report that spermine synthase (SMS), a polyamine biosynthetic enzyme, is overexpressed in CRC. Targeted disruption of SMS in CRC cells results in spermidine accumulation, which inhibits FOXO3a acetylation and allows subsequent translocation to the nucleus to transcriptionally induce expression of the proapoptotic protein Bim. However, this induction is blunted by MYC-driven expression of miR-19a and miR-19b that repress Bim production. Pharmacological or genetic inhibition of MYC activity in SMS-depleted CRC cells dramatically induces Bim expression and apoptosis …

Helicobacter Pylori Pathophysiology, Alisha Smith

Nursing Student Class Projects (Formerly MSN)

Abstract

This poster provides current research evidence on Helicobacter Pylori pathophysiology, treatment guidelines, and the potential etiology of associated disorders. The purpose is to provide a detailed overview of the functional changes within the intestinal cells caused by the microorganism. Furthermore, explaining of the mechanism and clinical manifestations of symptoms. The research focuses on risk factors, transmission, diagnostic evaluation, and the implications for nursing care. The best-available evidence offers concrete data examining the detrimental effects of the immune and inflammatory response stimulated by H. pylori. A description of the functional structures of H. pylori and its’ ability to survive. …

The Society Of Abdominal Radiology At 10 Years: Reflections, Status Report, And Look To The Future, Manju Ambelil, David M Saulino, Atilla Ertan, Andrew W Dupont, Mamoun Younes

Faculty, Staff and Student Publications

CONTEXT.—: Recent studies examining immunohistochemical staining of colorectal biopsies for cytomegalovirus (CMV) reported that some cases showed only occasional small positive nuclei that were called equivocal for CMV.

OBJECTIVES.—: To determine the extent and clinical significance of equivocal CMV staining in colorectal biopsies.

DESIGN.—: Two-hundred twenty-one consecutive cases of colon and rectal biopsies that were stained for CMV by immunohistochemistry were retrieved from our files and reviewed. Staining results were recorded as negative, unequivocal, or equivocal. Results were correlated with clinicopathologic data, results of polymerase chain reaction studies for CMV, and treatment history.

RESULTS.—: Fifty-two cases (24% of all tested, …

Evaluation Of The Sharkcore, Benjamin L. Witt, Rachel E. Factor, Barbara E. Chadwick, Justin Caron, Ali A. Siddiqui, Douglas G. Adler

Division of Gastroenterology and Hepatology Faculty Papers

Background and Objectives:

EUS guided core biopsy was once rarely performed but is now entering mainstream practice. Neuroendocrine tumors often warrant core biopsy as sufficient tissue must be obtained to allow for special staining to ensure a correct diagnosis. Traditionally these lesions were sampled with FNA needles. We performed a retrospective pilot study to evaluate the clinical value and efficacy of the a new EUS core needle biopsy needle as compared to a standard EUS FNA needle in the evaluation of patients with known or suspected neuroendocrine tumors.

Methods:

A retrospective analysis of the first 10 patients (between January 2015 …

Direct Detection Of Shigella In Stool Specimens By Use Of A Metagenomic Approach, Jie Liu, Mathieu Almeida, Furqan Kabir, Sadia Shakoor, Shahida Qureshi, Anita K. M. Zaidi, Shan Li, Boubou Tamboura, Samba O. Sow, Inacio Mandomando

Department of Paediatrics and Child Health

The underestimation of Shigella species as a cause of childhood diarrhea disease has become increasingly apparent with quantitative PCR (qPCR)-based diagnostic methods versus culture. We sought to confirm qPCR-based detection of Shigella via a metagenomics approach. Three groups of samples were selected from diarrheal cases from the Global Enteric Multicenter Study: nine Shigella culture-positive and qPCR-positive (culture⁺ qPCR⁺) samples, nine culture-negative but qPCR-positive (culture^- qPCR⁺) samples, and nine culture-negative and qPCR-negative (culture^- qPCR^-) samples. Fecal DNA was sequenced using paired-end Illumina HiSeq, whereby 3.26 × 10⁸ ± 5.6 × 10 …

A Gut Pathobiont Synergizes With The Microbiota To Instigate Inflammatory Disease Marked By Immunoreactivity Against Other Symbionts But Not Itself, João Carlos Gomes-Neto, Hatem Kittana, Sara Mantz, Rafael R. Segura Munoz, Robert J. Schmaltz, Laure B. Bindels, Jennifer L. Clarke, Jesse M. Hostetter, Andrew K. Benson, Jens Walter, Amanda Ramer-Tait

Department of Food Science and Technology: Faculty Publications

Inflammatory bowel diseases (IBD) are likely driven by aberrant immune responses directed against the resident microbiota. Although IBD is commonly associated with a dysbiotic microbiota enriched in putative pathobionts, the etiological agents of IBD remain unknown. Using a pathobiont-induced intestinal inflammation model and a defined bacterial community, we provide new insights into the immune-microbiota interactions during disease. In this model system, the pathobiont Helicobacter bilis instigates disease following sub-pathological dextran sulfate sodium treatment. We show that H. bilis causes mild inflammation in mono-associated mice, but severe disease in the presence of a microbiota, demonstrating synergy between the pathobiont and microbiota …

Intrahepatic Cholangiocarcinoma Presenting As Li-Rads 5 "Hcc", Raja K. Dhanekula, Md, Donald Mitchell, Md, John Farber, Md, Ashwin R. Sama, Md, Jesse M. Civan, Md

Division of Gastroenterology and Hepatology Posters

Background

• Hepatocellular Carcinoma (HCC), if within Milan Criteria, is an indication for liver transplantation.

• In contrast, intrahepatic cholangiocarcinoma (IHCC) is a contra-indication to liver transplantation due to high rates of recurrence.

• LI-RADS 5 classification (synonymous with OPTN-5) carries a near 100% positive predictive value for HCC, allowing prioritization of patients for liver transplantation without histological confirmation.

• The “LI-RADS M” classification indicates the presence of malignancy not meeting diagnostic criteria for HCC. In theory, IHCC lesions should be identified as LI-RADS M and not LI-RADS 5.

Dome-Type Carcinoma Of The Ascending Colon: A Case Report, Patrick Hickey Do, Shanth A. Goonewardene Md, Shashin Shah Md, Hiral N. Shah Md, Anthony G. Auteri Md

Department of Medicine

No abstract provided.

Intimin Likely Used To Cause Disease During Competition With Commensal Escherichia Coli, Dominique J. Richburg

Senior Honors Theses

The intimin gene in the Locus of Enterocyte Effacement (LEE) island of pathogenicity is the primary attachment mechanism in Citrobacter rodentium. Intimin is a bacterial adhesin (protein) that attaches to obtain a niche/nutrient and thrive within the intestine. Intimin was deleted within C. rodentium to study colonization and pathogenesis in the murine intestine. Additionally, C. rodentium is an attaching/effacing pathogen, and a useful murine model in understanding Enterohemorrhagic Escherichia coli (EHEC) infection in humans. E. coli and C. rodentium cause gastroenteritis in humans and mice, respectively. C. rodentium is a murine pathogen commonly used to model gastrointestinal disease because …

Pathogen-Specific Burdens Of Community Diarrhoea In Developing Countries: A Multisite Birth Cohort Study (Mal-Ed), Sadia Shakoor, Shahida Qureshi, Furqan Kabir, Anita K. M. Zaidi, Zulfiqar Ahmed Bhutta, Imran Ahmed, Didar Alam, Syed Asad Ali, Muneera Rasheed, Sajid Bashir Soofi, Ali Turab, Aisha Khizar Yousafzai

Department of Pathology and Laboratory Medicine

Background: Most studies of the causes of diarrhoea in low-income and middle-income countries have looked at severe disease in people presenting for care, and there are few estimates of pathogen-specific diarrhoea burdens in the community.
Methods: We undertook a birth cohort study with not only intensive community surveillance for diarrhoea but also routine collection of non-diarrhoeal stools from eight sites in South America, Africa, and Asia. We enrolled children within 17 days of birth, and diarrhoeal episodes (defined as maternal report of three or more loose stools in 24 h, or one loose stool with visible blood) were identified through …

Undifferentiated Carcinoma With Osteoclast-Like Giant Cells Of The Pancreatic Tail, Patrick Hickey Do, Ranjit R. Nair Md, Victoria A. Loven Md, Jeffrey Brodsky Md, Hiral N. Shah Md

Department of Medicine

No abstract provided.

Sessile Serrated Adenomas In The Proximal Colon Are Likely To Be Flat, Large And Occur In Smokers, Tarun Rustagi, Priya Rangasamy, Matthew Myers, Melinda Sanders, Haleh Vaziri, George Y. Wu, John W. Birk, Petr Protiva, Joseph C. Anderson

Dartmouth Scholarship

Aim: To examine the epidemiology and the morphology of the proximal sessile serrated adenomas (SSAs).

Methods: We conducted a retrospective study to identify patients with SSAs using a university-based hospital pathology database query from January 2007 to April 2011. Data collected included: age, gender, ethnicity, body mass index, diabetes, smoking, family history of colorectal cancer, aspirin, and statin use. We collected data on morphology of SSAs including site (proximal or distal), size, and endoscopic appearance (flat or protuberant). We also compared proximal SSAs to proximal tubular adenomas detected during same time period.

A Conserved Tissue-Specific Homeodomain-Less Isoform Of Meis1 Is Downregulated In Colorectal Cancer., Richard C Crist, Jacquelyn J Roth, Scott A Waldman, Arthur M Buchberg

Department of Microbiology and Immunology Faculty Papers

Colorectal cancer is one of the most common cancers in developed nations and is the result of both environmental and genetic factors. Many of the genetic lesions observed in colorectal cancer alter expression of homeobox genes, which encode homeodomain transcription factors. The MEIS1 homeobox gene is known to be involved in several hematological malignancies and solid tumors and recent evidence suggests that expression of the MEIS1 transcript is altered in colorectal cancer. Despite this potential connection, little is known about the role of the gene in the intestines. We probed murine gastrointestinal tissue samples with an N-terminal Meis1 antibody, revealing …

Response Of Imitanib Meysylate In Patients With Gastrointestinal Stromal Cell Tumour, Abdullah Ladha, Mohammad Usman Shaikh

Department of Pathology and Laboratory Medicine

In this study, the response of Imitanib Mesylate in patients with Gastro-intestinal stromal cell tumour (GIST) was assessed. GIST results from a mutation in one of the receptor protein tyrosine kinases. Imitanib Mesylate, a tyrosine kinase inhibitor, has emerged as a promising new treatment for GISTs. Total 16 cases were reviewed. Diagnosis was based on biopsy and immunohistochemistry. Response assessment was done using CT scans, at a median duration of 4 months. The median age of the patients was 52 years, Majority were male (n=14). Most common presenting complaint was abdominal pain (n=7). Commonest primary site was stomach (n=7), Liver …

Role Of Rapid Urease Test And Histopathology In The Diagnosis Of Helicobacter Pylori Infection In A Developing Country, Javed Yakoob, Wasim Jafri, Shahab Abid, Zaigham Abbas, Saeed Hamid, Muhammad Islam, Kashif Anis, Hasnain Ali Shah, Hizbullah Shaikh

Section of Gastroenterology

Background

The aim of this study was to determine the effect of commonly self-prescribed proton pump inhibitors (PPI) on the results of rapid urease test and histology for the diagnosis of H. pylori infection.

Methods

One hundred-nine consecutive patients with dyspeptic symptoms attending the endoscopy suite were enrolled in this study. Antrum biopsy specimens were collected at endoscopy for the rapid urease test (Pronto Dry, Medical Instrument Corp, France) and histopathology. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and like-hood ratio of a positive and negative of Pronto Dry test were compared against histology. The gold standard …

Trefoil Factor 2 (Tff2) Deficiency In Murine Digestive Tract Influences The Immune System, M. Baus- Loncar, J. Schmid, El-Nasir Lalani, I. Rosewell, R. A. Goodlad, H. G.W. Stamp, N. Blin, T. Kayademir

Department of Pathology and Laboratory Medicine

Background & Aims:

The gastrointestinal trefoil factor family (TFF1, TFF2, TFF3) peptides are considered to play an important role in maintaining the integrity of the mucosa. The physiological role of TFF2 in the protection of the GI tract was investigated in TFF2 deficiency.

Methods:

TFF2-/- mice were generated and differential expression of various genes was assessed by using a mouse expression microarray, quantitative real time PCR, Northern blots or immunohistochemistry.

Results:

On an mRNA level we found 128 differentially expressed genes. We observed modulation of a number of crucial genes involved in innate and adaptive immunity in the TFF2-/- mice. …

Gastric Carcinoma With Lymphoid Stroma: Association With Epstein Virus Genome Demonstrated By Pcr, Irshad N. Soomro, Samina Noorali, Syed Abdul Aziz, Suhail Muzaffar, Shahid Pervez, Akbar S. Hussainy, Tariq Moatter

Department of Pathology and Laboratory Medicine

No abstract provided.