Inflammation is an Independent Risk Factor for Colonic Neoplasia in Patients with Ulcerative Colitis: a Case–Control Study
01 Dec 2013-Clinical Gastroenterology and Hepatology (Clin Gastroenterol Hepatol)-Vol. 11, Iss: 12, pp 1601-1608
TL;DR: In a case-control study, increased inflammation is associated with CRN in patients with UC and use of immune modulators reduced the risk for CRN, indicating that these drugs have chemoprotective effects.
About: This article is published in Clinical Gastroenterology and Hepatology.The article was published on 2013-12-01 and is currently open access. It has received 233 citations till now. The article focuses on the topics: Primary sclerosing cholangitis & Inflammatory bowel disease.
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University of Porto1, University of Bologna2, Sheba Medical Center3, University of Milan4, Catholic University of the Sacred Heart5, Semmelweis University6, Medical University of Graz7, Pennine Acute Hospitals NHS Trust8, Seconda Università degli Studi di Napoli9, University of Cambridge10, Imperial College London11, Cleveland Clinic12
TL;DR: This research presents a meta-analyses of Gastroenterology and Hepatology at the cellular and molecular level, which shows clear trends in the development of immune-oncology-metabolical pathways towards “clinically checkpoints”.
Abstract: aDepartment of Pharmacology and Therapeutics, University of Porto; MedInUP, Centre for Drug Discovery and Innovative Medicines; Centro Hospitalar São João, Porto, Portugal bIBD Unit, DIMEC, University of Bologna, Bologna, Italy cDepartment of Gastroenterology and Hepatology, Chaim Sheba Medical Center, Tel Hashomer, Israel dGastrointestinal Unit ASST Fatebenefratelli Sacco—University of Milan—Milan, Italy eIBD Unit Complesso Integrato Columbus, Gastroenterological and Endocrino-Metabolical Sciences Department, Fondazione Policlinico Universitario Gemelli Universita’ Cattolica del Sacro Cuore, Rome, Italy fDepartment of Gastroenterology, IBD Unit, University Hospital Santiago De Compostela (CHUS), A Coruña, Spain gDepartment of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark hFirst Department of Medicine, Semmelweis University, Budapest, Hungary iIBD Unit, St Mark’s Hospital, Middlesex, UK jDepartment of Gastroenterology, University Hospital of Ghent, Ghent, Belgium kInstitute of Pathology, Medical University of Graz, Graz, Austria lDepartment of Gastroenterology, Pennine Acute Hospitals NHS Trust; Institute of Inflammation and Repair, University of Manchester, Manchester, UK mUnit of General Surgery, Second University of Naples, Napoli, Italy nMaria Skłodowska-Curie Memorial Cancer Centre and Institute of Oncology, Department of Oncological Gastroenterology Warsaw; Medical Centre for Postgraduate Education, Department of Gastroenterology, Hepatology and Clinical Oncology, Warsaw, Poland oDepartment of Medicine, University of Cambridge, Cambridge, UK pImperial College London; Chelsea and Westminster Hospital, London, UK qDepartment of Pathobiology /NC22, Lerner Research Institute; Department of Gastroenterology, Hepatology and Nutrition/A3, Digestive Disease and Surgery Institute, Cleveland Clinic Foundation, Cleveland, OH, USA
1,214 citations
TL;DR: These guidelines indicate the preferred approach to the management of adults with UC and represent the official practice recommendations of the American College of Gastroenterology.
755 citations
TL;DR: The wide range of cancers associated with inflammatory bowel disease and the drugs used to manage them are reviewed and surveillance recommendations are presented.
Abstract: This article reviews the wide range of cancers associated with inflammatory bowel disease and the drugs used to manage them. Surveillance recommendations are presented.
511 citations
TL;DR: This English version was produced and edited based on the existing updated guidelines for ulcerative colitis and Crohn’s disease in Japanese, developed with the basic concept of the Grading of Recommendations Assessment, Development, and Evaluation system.
Abstract: Inflammatory bowel disease (IBD) is a chronic disorder involving mainly the intestinal tract, but possibly other gastrointestinal and extraintestinal organs. Although etiology is still uncertain, recent knowledge in pathogenesis has accumulated, and novel diagnostic and therapeutic modalities have become available for clinical use. Therefore, the previous guidelines were urged to be updated. In 2016, the Japanese Society of Gastroenterology revised the previous versions of evidence-based clinical practice guidelines for ulcerative colitis (UC) and Crohn’s disease (CD) in Japanese. A total of 59 clinical questions for 9 categories (1. clinical features of IBD; 2. diagnosis; 3. general consideration in treatment; 4. therapeutic interventions for IBD; 5. treatment of UC; 6. treatment of CD; 7. extraintestinal complications; 8. cancer surveillance; 9. IBD in special situation) were selected, and a literature search was performed for the clinical questions with use of the MEDLINE, Cochrane, and Igaku Chuo Zasshi databases. The guidelines were developed with the basic concept of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) system. Recommendations were made using Delphi rounds. This English version was produced and edited based on the existing updated guidelines in Japanese.
400 citations
TL;DR: In this article, the authors developed a guideline for the management of moderate-to-severe UC using the GRADE framework and in adherence to the standards established by the Institute of Medicine for the development of trustworthy guidelines.
286 citations
References
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TL;DR: A general statistical methodology for the analysis of multivariate categorical data arising from observer reliability studies is presented and tests for interobserver bias are presented in terms of first-order marginal homogeneity and measures of interob server agreement are developed as generalized kappa-type statistics.
Abstract: This paper presents a general statistical methodology for the analysis of multivariate categorical data arising from observer reliability studies. The procedure essentially involves the construction of functions of the observed proportions which are directed at the extent to which the observers agree among themselves and the construction of test statistics for hypotheses involving these functions. Tests for interobserver bias are presented in terms of first-order marginal homogeneity and measures of interobserver agreement are developed as generalized kappa-type statistics. These procedures are illustrated with a clinical diagnosis example from the epidemiological literature.
64,109 citations
"Inflammation is an Independent Risk..." refers methods in this paper
...Kappa statistics were calculated to assess interobserver agreement between the 2 pathologists.(12) Conditional logistic regression was used to examine the relationship of inflammation score and other clinical parameters to the risk of CRN....
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TL;DR: Patients with moderate-to-severe active ulcerative colitis treated with infliximab at weeks 0, 2, and 6 and every eight weeks thereafter were more likely to have a clinical response at weeks 8, 30, and 54 than were those receiving placebo.
Abstract: Background Infliximab, a chimeric monoclonal antibody directed against tumor necrosis factor α, is an established treatment for Crohn's disease but not ulcerative colitis. Methods Two randomized, double-blind, placebo-controlled studies — the Active Ulcerative Colitis Trials 1 and 2 (ACT 1 and ACT 2, respectively) — evaluated the efficacy of infliximab for induction and maintenance therapy in adults with ulcerative colitis. In each study, 364 patients with moderate-to-severe active ulcerative colitis despite treatment with concurrent medications received placebo or infliximab (5 mg or 10 mg per kilogram of body weight) intravenously at weeks 0, 2, and 6 and then every eight weeks through week 46 (in ACT 1) or week 22 (in ACT 2). Patients were followed for 54 weeks in ACT 1 and 30 weeks in ACT 2. Results In ACT 1, 69 percent of patients who received 5 mg of infliximab and 61 percent of those who received 10 mg had a clinical response at week 8, as compared with 37 percent of those who received placebo (P<0...
3,345 citations
TL;DR: Using new meta-analysis techniques, the risk of CRC in UC by decade of disease and defined the risk in pancolitics and children was determined and how risk varies with geography was estimated.
Abstract: BACKGROUND AND AIMS Controversy surrounds the risk of colorectal cancer (CRC) in ulcerative colitis (UC). Many studies have investigated this risk and reported widely varying rates. METHODS A literature search using Medline with the explosion of references identified 194 studies. Of these, 116 met our inclusion criteria from which the number of patients and cancers detected could be extracted. Overall pooled estimates, with 95% confidence intervals (CI), of cancer prevalence and incidence were obtained using a random effects model on either the log odds or log incidence scale, as appropriate. RESULTS The overall prevalence of CRC in any UC patient, based on 116 studies, was estimated to be 3.7% (95% CI 3.2–4.2%). Of the 116 studies, 41 reported colitis duration. From these the overall incidence rate was 3/1000 person years duration (pyd), (95% CI 2/1000 to 4/1000). The overall incidence rate for any child was 6/1000 pyd (95% CI 3/1000 to 13/1000). Of the 41 studies, 19 reported results stratified into 10 year intervals of disease duration. For the first 10 years the incidence rate was 2/1000 pyd (95% CI 1/1000 to 2/1000), for the second decade the incidence rate was estimated to be 7/1000 pyd (95% CI 4/1000 to 12/1000), and in the third decade the incidence rate was 12/1000 pyd (95% CI 7/1000 to 19/1000). These incidence rates corresponded to cumulative probabilities of 2% by 10 years, 8% by 20 years, and 18% by 30 years. The worldwide cancer incidence rates varied geographically, being 5/1000 pyd in the USA, 4/1000 pyd in the UK, and 2/1000 pyd in Scandinavia and other countries. Over time the cancer risk has increased since 1955 but this finding was not significant (p=0.8). CONCLUSIONS Using new meta-analysis techniques we determined the risk of CRC in UC by decade of disease and defined the risk in pancolitics and children. We found a non-significant increase in risk over time and estimated how risk varies with geography.
2,627 citations
"Inflammation is an Independent Risk..." refers background in this paper
...Unfortunately, no retrospective studies of UC therapies and potential chemoprotective effects to reduce CRN risk considered degree of inflammation as a confounding variable.(1,9,10) Thus, the aim of this study was to comprehensively evaluate the risk of CRN in UC by measuring the degree of histologic inflammation over time and adjusting for therapy exposures and other known risk factors....
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TL;DR: Observations of mice genetically prone to inflammatory bowel disease also develop colorectal cancer especially in the presence of bacterial colonization offer compelling support for the role of inflammation in colon carcinogenesis.
Abstract: Patients with ulcerative colitis and Crohn's disease are at increased risk for developing colorectal cancer. To date, no known genetic basis has been identified to explain colorectal cancer predisp...
1,213 citations
TL;DR: In long-standing extensive ulcerative colitis, the severity of colonic inflammation is an important determinant of the risk of colorectal neoplasia and endoscopic and histological grading of inflammation could allow better risk stratification for surveillance programs.
1,134 citations
"Inflammation is an Independent Risk..." refers background or result in this paper
...RESULTS: Cases and controls were similar in numbers of procedures and biopsies, exposure to steroids or mesalamine, smoking status, and family history of CRN....
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...However, only histologic degree of inflammation remained significantly associated with CRN on multivariate analysis.(7) Similarly, a retrospective review of 418 UC patients, of whom 65 had CRN, at Mt Sinai Medical Center found that inflammation was associated with high-grade dysplasia or cancer....
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...We investigated the effects of inflammation, therapies, and characteristics of patients with UC on their risk for CRN. METHODS: We collected data from 141 patients with UC without CRN (controls) and 59 matched pa- tients with UC who developed CRN (cases), comparing disease extent and duration and patients’ ages....
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...However, previous studies did not address the duration of inflammation or the effects of therapy on risk for CRN....
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...Kappa statistics were calculated to assess interobserver agreement between the 2 pathologists.12 Conditional logistic regression was used to examine the relationship of inflammation score and other clinical parameters to the risk of CRN....
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