Barrett's Esophagus (With Or Without Dysplasia)
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Microsatellite Instability in Colorectal Cancer Liquid Biopsy—Current Updates on Its Potential in Non-Invasive Detection, Prognosis and As a Predictive Marker
diagnostics Review Microsatellite Instability in Colorectal Cancer Liquid Biopsy—Current Updates on Its Potential in Non-Invasive Detection, Prognosis and as a Predictive Marker Francis Yew Fu Tieng 1 , Nadiah Abu 1, Learn-Han Lee 2,* and Nurul-Syakima Ab Mutalib 1,2,3,* 1 UKM Medical Molecular Biology Institute (UMBI), Universiti Kebangsaan Malaysia, Kuala Lumpur 56000, Malaysia; [email protected] (F.Y.F.T.); [email protected] (N.A.) 2 Novel Bacteria and Drug Discovery Research Group, Microbiome and Bioresource Research Strength, Jeffrey Cheah School of Medicine and Health Sciences, Monash University Malaysia, Selangor 47500, Malaysia 3 Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Kuala Lumpur 50300, Malaysia * Correspondence: [email protected] (L.-H.L.); [email protected] (N.-S.A.M.); Tel.: +60-391459073 (N.-S.A.M.) Abstract: Colorectal cancer (CRC) is the third most commonly-diagnosed cancer in the world and ranked second for cancer-related mortality in humans. Microsatellite instability (MSI) is an indicator for Lynch syndrome (LS), an inherited cancer predisposition, and a prognostic marker which predicts the response to immunotherapy. A recent trend in immunotherapy has transformed cancer treatment to provide medical alternatives that have not existed before. It is believed that MSI-high (MSI-H) CRC patients would benefit from immunotherapy due to their increased immune infiltration and higher neo-antigenic loads. MSI testing such as immunohistochemistry (IHC) and PCR MSI assay Citation: Tieng, F.Y.F.; Abu, N.; Lee, has historically been a tissue-based procedure that involves the testing of adequate tissue with a high L.-H.; Ab Mutalib, N.-S. -
Short Course 10 Metaplasia in The
0 3: 436-446 Rev Esp Patot 1999; Vol. 32, N © Prous Science, SA. © Sociedad Espajiola de Anatomia Patot6gica Short Course 10 © Sociedad Espafiola de Citologia Metaplasia in the gut Chairperson: NA. Wright, UK. Co-chairpersons: G. Coggi, Italy and C. Cuvelier, Belgium. Overview of gastrointestinal metaplasias only in esophagus but also in the duodenum, intestine, gallbladder and even in the pancreas. Well established is columnar metaplasia J. Stachura of esophageal squamous epithelium. Its association with increased risk of esophageal cancer is widely recognized. Recent develop- Dept. of Pathomorphology, Jagiellonian University ments have suggested, however, that only the intestinal type of Faculty of Medicine, Krakdw, Poland. metaplastic epithelium (classic Barrett’s esophagus) predisposes to cancer. Another field of studies is metaplasia in the short seg- ment at the esophago-cardiac junction, its association with Metaplasia is a reversible change in which one aduit cell type is Helicobacter pylon infection and/or reflux disease and intestinal replaced by another. It is always associated with some abnormal metaplasia in the cardiac and fundic areas. stimulation of tissue growth, tissue regeneration or excessive hor- Studies on gastric mucosa metaplasia could be divided into monal stimulation. Heterotopia, on the other hand, takes place dur- those concerned with pathogenesis and detailed structural/func- ing embryogenesis and is usually supposed not to be associated tional features and those concerned with clinical significance. with tissue damage. Pancreatic acinar cell clusters in pediatric gas- We know now that gastric mucosa may show not only complete tric mucosa form another example of aberrant cell differentiation. and incomplete intestinal metaplasia but also others such as ciliary Metaplasia is usually divided into epithelial and connective tis- and pancreatic metaplasia. -
Hyperplasia (Growth Factors
Adaptations Robbins Basic Pathology Robbins Basic Pathology Robbins Basic Pathology Coagulation Robbins Basic Pathology Robbins Basic Pathology Homeostasis • Maintenance of a steady state Adaptations • Reversible functional and structural responses to physiologic stress and some pathogenic stimuli • New altered “steady state” is achieved Adaptive responses • Hypertrophy • Altered demand (muscle . hyper = above, more activity) . trophe = nourishment, food • Altered stimulation • Hyperplasia (growth factors, . plastein = (v.) to form, to shape; hormones) (n.) growth, development • Altered nutrition • Dysplasia (including gas exchange) . dys = bad or disordered • Metaplasia . meta = change or beyond • Hypoplasia . hypo = below, less • Atrophy, Aplasia, Agenesis . a = without . nourishment, form, begining Robbins Basic Pathology Cell death, the end result of progressive cell injury, is one of the most crucial events in the evolution of disease in any tissue or organ. It results from diverse causes, including ischemia (reduced blood flow), infection, and toxins. Cell death is also a normal and essential process in embryogenesis, the development of organs, and the maintenance of homeostasis. Two principal pathways of cell death, necrosis and apoptosis. Nutrient deprivation triggers an adaptive cellular response called autophagy that may also culminate in cell death. Adaptations • Hypertrophy • Hyperplasia • Atrophy • Metaplasia HYPERTROPHY Hypertrophy refers to an increase in the size of cells, resulting in an increase in the size of the organ No new cells, just larger cells. The increased size of the cells is due to the synthesis of more structural components of the cells usually proteins. Cells capable of division may respond to stress by undergoing both hyperrtophy and hyperplasia Non-dividing cell increased tissue mass is due to hypertrophy. -
Neurological Manifestation of Sacral Tumors
Neurosurg Focus 15 (2):Article 1, 2003, Click here to return to Table of Contents Neurological manifestation of sacral tumors MICHAEL PAYER, M.D. Department of Neurosurgery, University Hopital of Geneva, Switzerland An extensive analysis of the existing literature concerning sacral tumors was conducted to characterize their clin- ical manifestations. Although certain specific manifestations can be attributed to some of the tumor types, a more general pattern of clinical presentation of an expansive sacral lesion can be elaborated. Local pain with or without pseudoradicular or radicular radiation is the most frequent initial symptom and is usually followed by the manifesta- tion of a lumbosacral sensorimotor deficit; bladder/bowel and/or sexual dysfunction appear throughout the natural course of disease. KEY WORDS • sacrum • tumor • lesion • neurological presentation All sacral and presacral tumors are rare.32,93 In one se- REVIEW OF SACRAL ANATOMY ries patients with these tumors were estimated to account for approximately one in 40,000 hospital admissions.93 Osseous Structures of the Sacrum Tumors arising from the bone of the sacrum are by far the The sacrum is a complex bone, comprising five sacral most frequent sacral tumors; chordomas are the most com- vertebrae that have fused. In its center lies the longitudi- mon and GCTs the second most common.20,46,50,61,74,81,98 nal sacral canal, which opens caudally posteriorly into the Although sacrococcygeal teratoma is the most common sacral hiatus, an incomplete posterior closure of the S-5 sacral tumor in neonates, it is very rare in adults.30,45,66 lamina. The thick anterior or pelvic face of the sacrum is The author conducted an extensive analysis of the exist- concave and contains four right- and left-sided anterior ing literature concerning tumors of the sacrum to charac- sacral foramina. -
The Diagnostic and Prognostic Value of a Liquid Biopsy for Esophageal Cancer: a Systematic Review and Meta-Analysis
cancers Review The Diagnostic and Prognostic Value of a Liquid Biopsy for Esophageal Cancer: A Systematic Review and Meta-Analysis Daisuke Matsushita 1,* , Takaaki Arigami 2 , Keishi Okubo 1, Ken Sasaki 1, Masahiro Noda 1, Yoshiaki Kita 1, Shinichiro Mori 1, Yoshikazu Uenosono 3, Takao Ohtsuka 1 and Shoji Natsugoe 4 1 Department of Digestive Surgery, Breast and Thyroid Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan; [email protected] (K.O.); [email protected] (K.S.); [email protected] (M.N.); [email protected] (Y.K.); [email protected] (S.M.); [email protected] (T.O.) 2 Department of Onco-biological Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8520, Japan; [email protected] 3 Department of Surgery, Jiaikai Imamura General Hospital, Kagoshima 890-0064, Japan; [email protected] 4 Department of Surgery, Gyokushoukai Kajiki Onsen Hospital, Aira 899-5241, Japan; [email protected] * Correspondence: [email protected]; Tel.: +81-99-275-5361; Fax: +81-99-265-7426 Received: 9 September 2020; Accepted: 18 October 2020; Published: 21 October 2020 Simple Summary: The “liquid biopsy” is a novel concept for detecting circulating biomarkers in the peripheral blood of patients with various cancers, including esophageal cancer. There are two main methods to identify circulating cancer related biomarkers such as morphological techniques or molecular biological techniques. -
Squamous Metaplasia of Normal and Carcinoma in Situ of HPV 16-Immortalized Human Endocervical Cells1
[CANCER RESEARCH 52. 4254-4260, August I, 1992] Squamous Metaplasia of Normal and Carcinoma in Situ of HPV 16-Immortalized Human Endocervical Cells1 Qi Sun, Kouichiro Tsutsumi, M. Brian Kelleher, Alan Pater, and Mary M. Pater2 Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, Newfoundland, Canada A1B ÌV6 ABSTRACT genomic DNA, most frequently of HPV 16, has been detected in 90% of the cervical carcinomas and are found to be actively The importance of cervical squamous metaplasia and human papil- expressed (6, 7). HPV 16 DNA has been used to transform lomavirus 16 (HPV 16) infection for cervical carcinoma has been well human foreskin and ectocervical keratinocytes (8, 9). It immor established. Nearly 87% of the intraepithelial neoplasia of the cervix occur in the transformation zone, which is composed of squamous meta- talizes human keratinocytes efficiently, producing cell clones plastic cells with unclear origin. HPV DNA, mostly HPV 16, has been with indefinite life span in culture. Different approaches have found in 90% of cervical carcinomas, but only limited experimental data been taken to examine the behavior of these immortalized cell are available to discern the role of HPV 16 in this tissue specific onco- lines in conditions allowing squamous differentiation (10, 11). genesis. We have initiated in vivo studies of cultured endocervical cells After transplantation in vivo, the HPV 16-immortalized kerat as an experimental model system for development of cervical neoplasia. inocytes retain thépotential for squamous differentiation, Using a modified in vivo implantation system, cultured normal endocer forming abnormal epithelium without dysplastic changes at vical epithelial cells formed epithelium resembling squamous metapla early passages and with various dysplastic changes only after sia, whereas those immortalized by HPV 16 developed into lesions long periods of time in culture (10). -
Surgical and Molecular Pathology of Barrett Esophagus Sherma Zibadi, MD, Phd, and Domenico Coppola, MD
Grading is essential for treatment plans, follow-up visits, and therapeutic interventions. Three Layers of Paint. Photograph courtesy of Craig Damlo. www.soapboxrocket.com. Surgical and Molecular Pathology of Barrett Esophagus Sherma Zibadi, MD, PhD, and Domenico Coppola, MD Background: Patients with Barrett esophagus (BE) are predisposed to developing dysplasia and cancer. Adenocarcinoma, which is associated with BE, is the most common type of esophageal tumor and, typically, it has an aggressive clinical course and a high rate of mortality. Methods: The English-language literature relating to tumor epidemiology, etiology, and the pathogenesis of BE was reviewed and summarized. Results: The role of pathologists in the diagnosis and pitfalls associated with grading Barrett dysplasia is addressed. Current molecular testing for Barrett neoplasia, as well as testing methods currently in develop- ment, is discussed, focusing on relevant tests for diagnosing tumor types, determining prognosis, and assessing therapeutic response. Conclusions: Grading is essential for developing appropriate treatment plans, follow-up visits, and therapeutic interventions for each patient. Familiarity with current molecular testing methods will help physicians correctly diagnose the disease and select the most appropriate therapy for each of their patients. Introduction tinal metaplasia are also defined as Barrett mucosa.1 Barrett mucosa refers to a metaplastic process in- Barrett esophagus (BE) is more common in men duced by the acid-peptic content of the stomach -
Bioactive Nutrients and Nutrigenomics in Age-Related Diseases
molecules Review Bioactive Nutrients and Nutrigenomics in Age-Related Diseases Tania Rescigno 1, Luigina Micolucci 2,3, Mario F. Tecce 1 and Anna Capasso 1,* 1 Department of Pharmacy, University of Salerno, Fisciano 84084, Italy; [email protected] (T.R.); [email protected] (M.F.T.) 2 Computational Pathology Unit, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona 60120, Italy; [email protected] 3 Laboratory of Experimental Pathology, Department of Clinical and Molecular Sciences, Università Politecnica delle Marche, Ancona 60120, Italy * Correspondence: [email protected]; Tel.: +39-089-989744 Academic Editor: Philippe Bulet Received: 18 November 2016; Accepted: 3 January 2017; Published: 8 January 2017 Abstract: The increased life expectancy and the expansion of the elderly population are stimulating research into aging. Aging may be viewed as a multifactorial process that results from the interaction of genetic and environmental factors, which include lifestyle. Human molecular processes are influenced by physiological pathways as well as exogenous factors, which include the diet. Dietary components have substantive effects on metabolic health; for instance, bioactive molecules capable of selectively modulating specific metabolic pathways affect the development/progression of cardiovascular and neoplastic disease. As bioactive nutrients are increasingly identified, their clinical and molecular chemopreventive effects are being characterized and systematic analyses encompassing the “omics” technologies (transcriptomics, proteomics and metabolomics) are being conducted to explore their action. The evolving field of molecular pathological epidemiology has unique strength to investigate the effects of dietary and lifestyle exposure on clinical outcomes. The mounting body of knowledge regarding diet-related health status and disease risk is expected to lead in the near future to the development of improved diagnostic procedures and therapeutic strategies targeting processes relevant to nutrition. -
Is Intestinal Metaplasia a Risk for Gastric Carcinoma? Carcinoma.3'4
604 LETTERS TO THE EDITOR Postgrad Med J: first published as 10.1136/pgmj.65.766.604 on 1 August 1989. Downloaded from monocytosis together with the presence of neutrophilic ing to Jass and Filipe in type I (complete), type IIA and type leucocytosis in peripheral blood analyses can be of some IIB (incomplete) in relation to the absence or presence in value to differentiate both tuberculous and listeric meningitis these last two types ofsulphomucins in the columnar mucous from partially-treated bacterial meningitis. cells.8 In 1985 the types IIA and IIB were redefined as II and III respectively, confirming the importance of type III in the P. Domingo screening of gastric carcinoma.9 In 19 cases, that is 8.5% of J. Colomina the patients we considered, we observed metaplasia of type Department of Internal Medicine, IIB or III. Hospital de la Santa Creu i Sant Pau, In this study we noticed the appearance of gastric car- Autonomous University of Barcelona, cinoma and more precisely of early gastric cancer in only 2 Barcelona, Spain. (0.9%) of the whole series of cases. Taking into account that the evolution ofgastric ulcer into carcinoma is not more than 1% ofthe patients'0 and referring to our data, we can say that References intestinal metaplasia type IIB or III in the stomach does not appear to be a clear element of neoplastic risk. 1. Hearmon, C.J. & Ghosh, S.K. Listeria monocytogenes meningitis in previously healthy adults. Postgrad Med J 1989, 65: 74-78. Paolo Sossai 2. Bach, M.C. & Davis, K.M. -
Chapter 1 Cellular Reaction to Injury 3
Schneider_CH01-001-016.qxd 5/1/08 10:52 AM Page 1 chapter Cellular Reaction 1 to Injury I. ADAPTATION TO ENVIRONMENTAL STRESS A. Hypertrophy 1. Hypertrophy is an increase in the size of an organ or tissue due to an increase in the size of cells. 2. Other characteristics include an increase in protein synthesis and an increase in the size or number of intracellular organelles. 3. A cellular adaptation to increased workload results in hypertrophy, as exemplified by the increase in skeletal muscle mass associated with exercise and the enlargement of the left ventricle in hypertensive heart disease. B. Hyperplasia 1. Hyperplasia is an increase in the size of an organ or tissue caused by an increase in the number of cells. 2. It is exemplified by glandular proliferation in the breast during pregnancy. 3. In some cases, hyperplasia occurs together with hypertrophy. During pregnancy, uterine enlargement is caused by both hypertrophy and hyperplasia of the smooth muscle cells in the uterus. C. Aplasia 1. Aplasia is a failure of cell production. 2. During fetal development, aplasia results in agenesis, or absence of an organ due to failure of production. 3. Later in life, it can be caused by permanent loss of precursor cells in proliferative tissues, such as the bone marrow. D. Hypoplasia 1. Hypoplasia is a decrease in cell production that is less extreme than in aplasia. 2. It is seen in the partial lack of growth and maturation of gonadal structures in Turner syndrome and Klinefelter syndrome. E. Atrophy 1. Atrophy is a decrease in the size of an organ or tissue and results from a decrease in the mass of preexisting cells (Figure 1-1). -
Histopathology of Barrett's Esophagus and Early-Stage
Review Histopathology of Barrett’s Esophagus and Early-Stage Esophageal Adenocarcinoma: An Updated Review Feng Yin, David Hernandez Gonzalo, Jinping Lai and Xiuli Liu * Department of Pathology, Immunology, and Laboratory Medicine, College of Medicine, University of Florida, Gainesville, FL 32610, USA; fengyin@ufl.edu (F.Y.); hernand3@ufl.edu (D.H.G.); jinpinglai@ufl.edu (J.L.) * Correspondence: xiuliliu@ufl.edu; Tel.: +1-352-627-9257; Fax: +1-352-627-9142 Received: 24 October 2018; Accepted: 22 November 2018; Published: 27 November 2018 Abstract: Esophageal adenocarcinoma carries a very poor prognosis. For this reason, it is critical to have cost-effective surveillance and prevention strategies and early and accurate diagnosis, as well as evidence-based treatment guidelines. Barrett’s esophagus is the most important precursor lesion for esophageal adenocarcinoma, which follows a defined metaplasia–dysplasia–carcinoma sequence. Accurate recognition of dysplasia in Barrett’s esophagus is crucial due to its pivotal prognostic value. For early-stage esophageal adenocarcinoma, depth of submucosal invasion is a key prognostic factor. Our systematic review of all published data demonstrates a “rule of doubling” for the frequency of lymph node metastases: tumor invasion into each progressively deeper third of submucosal layer corresponds with a twofold increase in the risk of nodal metastases (9.9% in the superficial third of submucosa (sm1) group, 22.0% in the middle third of submucosa (sm2) group, and 40.7% in deep third of submucosa (sm3) group). Other important risk factors include lymphovascular invasion, tumor differentiation, and the recently reported tumor budding. In this review, we provide a concise update on the histopathological features, ancillary studies, molecular signatures, and surveillance/management guidelines along the natural history from Barrett’s esophagus to early stage invasive adenocarcinoma for practicing pathologists. -
Precision Medicine Approaches to Prevent Gastric Cancer
Gut and Liver https://doi.org/10.5009/gnl19257 pISSN 1976-2283 eISSN 2005-1212 Review Article Precision Medicine Approaches to Prevent Gastric Cancer Juntaro Matsuzaki1, Hitoshi Tsugawa2, and Hidekazu Suzuki3 1Division of Gastroenterology and Hepatology, Department of Internal Medicine, 2Department of Biochemistry, Keio University School of Medicine, Tokyo, and 3Department of Gastroenterology and Hepatology, Tokai University School of Medicine, Isehara, Japan Article Info Gastric cancer remains one of the most common causes of cancer-related death worldwide, Received July 22, 2019 although the incidence is declining gradually. The primary risk factor for gastric cancer is Helico- Revised October 18, 2019 bacter pylori infection. The Kyoto global consensus report recommends eradication of H. pylori Accepted November 15, 2019 in all infected patients. However, because it is difficult to stratify the risk of carcinogenesis among Published online January 6, 2020 patients with a history of H. pylori infection, annual endoscopic surveillance is performed for everyone after eradication. This review summarizes the current approaches used to screen for Corresponding Author novel molecules that could assist in the diagnosis of gastric cancer and reduce mortality. Most Hidekazu Suzuki well-studied molecules are tissue protein biomarkers expressed by the gastric epithelium and as- ORCID https://orcid.org/0000-0002-8994-6163 sociated with metaplasia-dysplasia-carcinoma sequences. Other strategies focus on the origin of E-mail [email protected] cancer stem cell-related markers, such as CD44, and immune reaction-related markers, such as matrix metallopeptidases. Noninvasive methods such as blood-based approaches are more at- tractive. Serum pepsinogen levels predict the severity of gastric mucosal atrophy before H.