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3 results on '"Neil Shepherd"'

1. Identification of Prognostic Phenotypes of Esophageal Adenocarcinoma in 2 Independent Cohorts

Author

Tarek Sawas, Sarah Killcoyne, Prasad G. Iyer, Kenneth K. Wang, Thomas C. Smyrk, John B. Kisiel, Yi Qin, David A. Ahlquist, Anil K. Rustgi, Rui J. Costa, Moritz Gerstung, Rebecca C. Fitzgerald, David A. Katzka, Ayesha Noorani, Paul A.W. Edwards, Nicola Grehan, Barbara Nutzinger, Caitriona Hughes, Elwira Fidziukiewicz, Jan Bornschein, Shona MacRae, Jason Crawte, Gianmarco Contino, Xiaodun Li, Rachel de la Rue, Maria O’Donovan, Ahmad Miremad, Shalini Malhotra, Monika Tripathi, Simon Tavaré, Andy G. Lynch, Matthew Eldridge, Maria Secrier, Lawrence Bower, Ginny Devonshire, Juliane Perner, Sriganesh Jammula, Jim Davies, Charles Crichton, Nick Carroll, Peter Safranek, Andrew Hindmarsh, Vijayendran Sujendran, Stephen J. Hayes, Yeng Ang, Shaun R. Preston, Sarah Oakes, Izhar Bagwan, Vicki Save, Richard J.E. Skipworth, Ted R. Hupp, J. Robert O’Neill, Olga Tucker, Andrew Beggs, Philippe Taniere, Sonia Puig, Timothy J. Underwood, Fergus Noble, Jack Owsley, Hugh Barr, Neil Shepherd, Oliver Old, Jesper Lagergren, James Gossage, Andrew Davies, Fuju Chang, Janine Zylstra, Ula Mahadeva, Vicky Goh, Francesca D. Ciccarelli, Grant Sanders, Richard Berrisford, Catherine Harden, David Bunting, Mike Lewis, Ed Cheong, Bhaskar Kumar, Simon L. Parsons, Irshad Soomro, Philip Kaye, John Saunders, Laurence Lovat, Rehan Haidry, Victor Eneh, Laszlo Igali, Michael Scott, Sharmila Sothi, Sari Suortamo, Suzy Lishman, George B. Hanna, Christopher J. Peters, Anna Grabowska, and Richard Turkington

Subjects
Oncology, Male, medicine.medical_specialty, Esophageal Neoplasms, Survival, Adenocarcinoma, Article, 03 medical and health sciences, Barrett Esophagus, 0302 clinical medicine, Esophagus, Interquartile range, Internal medicine, medicine, Humans, Stage (cooking), Esophageal Adenocarcinoma, Aged, Neoplasm Staging, Proportional Hazards Models, Metaplasia, Hepatology, business.industry, Hazard ratio, Gastroenterology, Intestinal metaplasia, Middle Aged, medicine.disease, Prognosis, United Kingdom, United States, Intestines, medicine.anatomical_structure, Phenotype, 030220 oncology & carcinogenesis, Barrett's esophagus, Cohort, Etiology, Regression Analysis, 030211 gastroenterology & hepatology, business
Abstract

Background & Aims: Most patients with esophageal adenocarcinoma (EAC) present with de novo tumors. Although this could be due to inadequate screening strategies, the precise reason for this observation is not clear. We compared survival of patients with prevalent EAC with and without synchronous Barrett esophagus (BE) with intestinal metaplasia (IM) at the time of EAC diagnosis. Methods: Clinical data were studied using Cox proportional hazards regression to evaluate the effect of synchronous BE-IM on EAC survival independent of age, sex, TNM stage, and tumor location. We analyzed data from a cohort of patients with EAC from the Mayo Clinic (n=411; 203 with BE and IM) and a multicenter cohort from the United Kingdom (n=1417; 638 with BE and IM). Results: In the Mayo cohort, BE with IM had a reduced risk of death compared to patients without BE and IM (hazard ratio [HR] 0.44; 95% CI, 0.34–0.57; PConclusion: Two types of EAC can be characterized based on the presence or absence of BE. These findings could increase our understanding the etiology of EAC, and be used in management and prognosis of patients.

Published
2018
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2. The stem cell organisation, and the proliferative and gene expression profile of Barrett's epithelium, replicates pyloric-type gastric glands

Author

Danielle L Lavery, Anna M Nicholson, Richard Poulsom, Rosemary Jeffery, Alia Hussain, Laura J Gay, Janusz A Jankowski, Sebastian S Zeki, Hugh Barr, Rebecca Harrison, James Going, Sritharan Kadirkamanathan, Peter Davis, Timothy Underwood, Marco R Novelli, Manuel Rodriguez–Justo, Neil Shepherd, Marnix Jansen, Nicholas A Wright, Stuart A C McDonald, and Pathology

Subjects
Pathology, medicine.medical_specialty, Mucin 5AC, Biology, digestive system, Receptors, G-Protein-Coupled, Barrett Esophagus, Esophagus, Cell Movement, Idoxuridine, Gastric glands, Biomarkers, Tumor, medicine, Gastric mucosa, Humans, education, Cell Proliferation, Nucleic Acid Synthesis Inhibitors, education.field_of_study, Gene Expression Profiling, Stem Cells, digestive, oral, and skin physiology, Gastroenterology, Trefoil factor 2, Intestinal metaplasia, A300, Pylorus, medicine.disease, Immunohistochemistry, digestive system diseases, Epithelium, Foveolar cell, Ki-67 Antigen, medicine.anatomical_structure, Gastric Mucosa, Disease Progression, Goblet Cells, Trefoil Factor-2, Trefoil Factor-3, Stem cell, Peptides
Abstract

Objective: Barrett's oesophagus shows appearances described as ‘intestinal metaplasia’, in structures called ‘crypts’ but do not typically display crypt architecture. Here, we investigate their relationship to gastric glands.\ud \ud Methods: Cell proliferation and migration within Barrett's glands was assessed by Ki67 and iododeoxyuridine (IdU) labelling. Expression of mucin core proteins (MUC), trefoil family factor (TFF) peptides and LGR5 mRNA was determined by immunohistochemistry or by in situ hybridisation, and clonality was elucidated using mitochondrial DNA (mtDNA) mutations combined with mucin histochemistry.\ud \ud Results: Proliferation predominantly occurs in the middle of Barrett's glands, diminishing towards the surface and the base: IdU dynamics demonstrate bidirectional migration, similar to gastric glands. Distribution of MUC5AC, TFF1, MUC6 and TFF2 in Barrett's mirrors pyloric glands and is preserved in Barrett's dysplasia. MUC2-positive goblet cells are localised above the neck in Barrett's glands, and TFF3 is concentrated in the same region. LGR5 mRNA is detected in the middle of Barrett's glands suggesting a stem cell niche in this locale, similar to that in the gastric pylorus, and distinct from gastric intestinal metaplasia. Gastric and intestinal cell lineages within Barrett's glands are clonal, indicating derivation from a single stem cell.\ud \ud Conclusions: Barrett's shows the proliferative and stem cell architecture, and pattern of gene expression of pyloric gastric glands, maintained by stem cells showing gastric and intestinal differentiation: neutral drift may suggest that intestinal differentiation advances with time, a concept critical for the understanding of the origin and development of Barrett's oesophagus.

Published
2014
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3. Evaluation of linear discriminant analysis for automated Raman histological mapping of esophageal high-grade dysplasia.

Author

Joanne Hutchings, Catherine Kendall, Neil Shepherd, Hugh Barr, and Nicholas Stone

Subjects
DISCRIMINANT analysis, HISTOLOGY, RAMAN effect, DIAGNOSIS, FEASIBILITY studies, ESOPHAGUS, PRINCIPAL components analysis
Abstract

Rapid Raman mapping has the potential to be used for automated histopathology diagnosis, providing an adjunct technique to histology diagnosis. The aim of this work is to evaluate the feasibility of automated and objective pathology classification of Raman maps using linear discriminant analysis. Raman maps of esophageal tissue sections are acquired. Principal component (PC)-fed linear discriminant analysis (LDA) is carried out using subsets of the Raman map data (6483 spectra). An overall (validated) training classification model performance of 97.7 (sensitivity 95.0 to 100 and specificity 98.6 to 100) is obtained. The remainder of the map spectra (131,672 spectra) are projected onto the classification model resulting in Raman images, demonstrating good correlation with contiguous hematoxylin and eosin (HE) sections. Initial results suggest that LDA has the potential to automate pathology diagnosis of esophageal Raman images, but since the classification of test spectra is forced into existing training groups, further work is required to optimize the training model. A small pixel size is advantageous for developing the training datasets using mapping data, despite lengthy mapping times, due to additional morphological information gained, and could facilitate differentiation of further tissue groups, such as the basal cellslamina propria, in the future, but larger pixels sizes (and faster mapping) may be more feasible for clinical application. [ABSTRACT FROM AUTHOR]

Published
2010
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