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Liu R, Li D, Haritunians T, Ruan Y, Daly MJ, Huang H, McGovern DP. Profiling the inflammatory bowel diseases using genetics, serum biomarkers, and smoking information. iScience 2023; 26:108053. [PMID: 37841595 PMCID: PMC10568094 DOI: 10.1016/j.isci.2023.108053] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/21/2023] [Revised: 07/28/2023] [Accepted: 09/22/2023] [Indexed: 10/17/2023] Open
Abstract
Crohn's disease (CD) and ulcerative colitis (UC) are two etiologically related yet distinctive subtypes of the inflammatory bowel diseases (IBD). Differentiating CD from UC can be challenging using conventional clinical approaches in a subset of patients. We designed and evaluated a novel molecular-based prediction model aggregating genetics, serum biomarkers, and tobacco smoking information to assist the diagnosis of CD and UC in over 30,000 samples. A joint model combining genetics, serum biomarkers and smoking explains 46% (42-50%, 95% CI) of phenotypic variation. Despite modest overlaps with serum biomarkers, genetics makes unique contributions to distinguishing IBD subtypes. Smoking status only explains 1% (0-6%, 95% CI) of the phenotypic variance suggesting it may not be an effective biomarker. This study reveals that molecular-based models combining genetics, serum biomarkers, and smoking information could complement current diagnostic strategies and help classify patients based on biologic state rather than imperfect clinical parameters.
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Affiliation(s)
- Ruize Liu
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Dalin Li
- F. Widjaja Family Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Talin Haritunians
- F. Widjaja Family Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
| | - Yunfeng Ruan
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Mark J. Daly
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Hailiang Huang
- Analytic and Translational Genetics Unit, Massachusetts General Hospital, Boston, MA 02114, USA
- Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA
| | - Dermot P.B. McGovern
- F. Widjaja Family Foundation Inflammatory Bowel and Immunobiology Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90048, USA
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Burisch J. Long-term disease course, cost and prognosis of inflammatory bowel disease: epidemiological studies of a European and a Danish inception cohort. APMIS 2023; 131 Suppl 147:1-46. [PMID: 37336790 DOI: 10.1111/apm.13334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/21/2023]
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Marabotto E, Kayali S, Buccilli S, Levo F, Bodini G, Giannini EG, Savarino V, Savarino EV. Colorectal Cancer in Inflammatory Bowel Diseases: Epidemiology and Prevention: A Review. Cancers (Basel) 2022; 14:cancers14174254. [PMID: 36077786 PMCID: PMC9454776 DOI: 10.3390/cancers14174254] [Citation(s) in RCA: 28] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 08/27/2022] [Accepted: 08/29/2022] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Colorectal cancer (CRC) is one of the most serious potential complications of inflammatory bowel diseases (IBDs). The aging of patients affected by IBDs makes this issue a challenge that will increasingly be faced by clinicians in clinical practice, especially in light of the poorer prognosis for CRC in this group of people when compared with the general population. In this review, we summarize the current epidemiology, risk factors and various prevention strategies proposed for CRC in patients with IBDs. Abstract Colorectal cancer (CRC) is currently the third most frequent form of malignancy and the second in terms of mortality. Inflammatory bowel diseases (IBDs) are recognized risk factors for this type of cancer. Despite a worldwide increase in the incidence of CRC, the risk of CRC-related death in IBD patients has declined over time, probably because of successful surveillance strategies, the use of more effective drugs in the management of remission and improved indications to colectomy. This notwithstanding, CRC 5-year survival in patients with IBD is poorer than in the general population. This review provides a summary of the epidemiological features, risk factors and various prevention strategies proposed for CRC in IBD patients. Moreover, there is a special focus on reporting and highlighting the various prevention strategies proposed by the most important international scientific societies, both in terms of chemoprevention and endoscopic surveillance. Indeed, in conducting the analysis, we have given attention to the current primary, secondary and tertiary prevention guidelines, attempting to emphasize unresolved research and clinical problems related to this topic in order to improve diagnostic strategies and management.
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Affiliation(s)
- Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, University of Genoa, 16132 Genoa, Italy
| | - Stefano Kayali
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, University of Genoa, 16132 Genoa, Italy
- Correspondence:
| | - Silvia Buccilli
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, University of Genoa, 16132 Genoa, Italy
| | - Francesca Levo
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, University of Genoa, 16132 Genoa, Italy
| | - Giorgia Bodini
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, University of Genoa, 16132 Genoa, Italy
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, University of Genoa, 16132 Genoa, Italy
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, University of Genoa, 16132 Genoa, Italy
| | - Edoardo Vincenzo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35137 Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università di Padova, 35128 Padua, Italy
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Quintanilla I, Jung G, Jimeno M, Lozano JJ, Sidorova J, Camps J, Carballal S, Bujanda L, Vera MI, Quintero E, Carrillo-Palau M, Cuatrecasas M, Castells A, Panés J, Ricart E, Moreira L, Balaguer F, Pellisé M. Differentially Deregulated MicroRNAs as Novel Biomarkers for Neoplastic Progression in Ulcerative Colitis. Clin Transl Gastroenterol 2022; 13:e00489. [PMID: 35404333 PMCID: PMC10476842 DOI: 10.14309/ctg.0000000000000489] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2021] [Accepted: 03/04/2022] [Indexed: 11/17/2022] Open
Abstract
INTRODUCTION Colorectal cancer (CRC) is a potentially life-threatening complication of long-standing ulcerative colitis (UC). MicroRNAs (miRNA) are epigenetic regulators that have been involved in the development of UC-associated CRC. However, their role as potential mucosal biomarkers of neoplastic progression has not been adequately studied. METHODS In this study, we analyzed the expression of 96 preselected miRNAs in human formalin-fixed and paraffin-embedded tissue of 52 case biopsies (20 normal mucosa, 20 dysplasia, and 12 UC-associated CRCs) and 50 control biopsies (10 normal mucosa, 21 sporadic adenomas, and 19 sporadic CRCs) by using Custom TaqMan Array Cards. For validation of deregulated miRNAs, we performed individual quantitative real-time polymerase chain reaction in an independent cohort of 50 cases (13 normal mucosa, 25 dysplasia, and 12 UC-associated CRCs) and 46 controls (7 normal mucosa, 19 sporadic adenomas, and 20 sporadic CRCs). RESULTS Sixty-four miRNAs were found to be differentially deregulated in the UC-associated CRC sequence. Eight of these miRNAs were chosen for further validation. We confirmed miR-31, -106a, and -135b to be significantly deregulated between normal mucosa and dysplasia, as well as across the UC-associated CRC sequence (all P < 0.01). Notably, these miRNAs also confirmed to have a significant differential expression compared with sporadic CRC (all P < 0.05). DISCUSSION UC-associated and sporadic CRCs have distinct miRNA expression patterns, and some miRNAs indicate early neoplastic progression.
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Affiliation(s)
- Isabel Quintanilla
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- National Cancer Institute, NIH, Bethesda, Maryland, USA
| | - Gerhard Jung
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Department of Gastroenterology, Hospital Clinic, Barcelona, Spain
- Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Mireya Jimeno
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Departament of Pathology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain
| | - Juan José Lozano
- Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Bioinformatics Platform, CIBEREHD, Barcelona, Spain
| | - Julia Sidorova
- Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Bioinformatics Platform, CIBEREHD, Barcelona, Spain
| | - Jordi Camps
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
| | - Sabela Carballal
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Department of Gastroenterology, Hospital Clinic, Barcelona, Spain
- Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Luis Bujanda
- Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Department of Gastroenterology, Biodonostia Health Research Institute, Universidad del País Vasco (UPV/EHU), San Sebastián, Spain
| | - Maria Isabel Vera
- Department of Gastroenterology, University Hospital Puerta de Hierro Majadahonda, Madrid, Spain
| | - Enrique Quintero
- Department of Gastroenterology, University Hospital of the Canary Islands, Santa Cruz de Tenerife, Spain
| | - Marta Carrillo-Palau
- Department of Gastroenterology, University Hospital of the Canary Islands, Santa Cruz de Tenerife, Spain
| | - Miriam Cuatrecasas
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Department of Pathology, Hospital Clinic, Barcelona, Spain
| | - Antoni Castells
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Department of Gastroenterology, Hospital Clinic, Barcelona, Spain
- Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Julià Panés
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Department of Gastroenterology, Hospital Clinic, Barcelona, Spain
- Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Elena Ricart
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Department of Gastroenterology, Hospital Clinic, Barcelona, Spain
- Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Leticia Moreira
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Department of Gastroenterology, Hospital Clinic, Barcelona, Spain
- Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Francesc Balaguer
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Department of Gastroenterology, Hospital Clinic, Barcelona, Spain
- Faculty of Medicine, University of Barcelona, Barcelona, Spain
| | - Maria Pellisé
- Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain
- Centro de Investigación Biomédica en Red, Enfermedades Hepáticas y Digestivas (CIBERehd), Barcelona, Spain
- Department of Gastroenterology, Hospital Clinic, Barcelona, Spain
- Faculty of Medicine, University of Barcelona, Barcelona, Spain
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Majumder S, Shivaji UN, Kasturi R, Sigamani A, Ghosh S, Iacucci M. Inflammatory bowel disease-related colorectal cancer: Past, present and future perspectives. World J Gastrointest Oncol 2022; 14:547-567. [PMID: 35321275 PMCID: PMC8919014 DOI: 10.4251/wjgo.v14.i3.547] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/21/2021] [Accepted: 02/27/2022] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease-related colorectal cancer (IBD-CRC) is one of the most serious complications of IBD contributing to significant mortality in this cohort of patients. IBD is often associated with diet and lifestyle-related gut microbial dysbiosis, the interaction of genetic and environmental factors, leading to chronic gut inflammation. According to the “common ground hypothesis”, microbial dysbiosis and intestinal barrier impairment are at the core of the chronic inflammatory process associated with IBD-CRC. Among the many underlying factors known to increase the risk of IBD-CRC, perhaps the most important factor is chronic persistent inflammation. The persistent inflammation in the colon results in increased proliferation of cells necessary for repair but this also increases the risk of dysplastic changes due to chromosomal and microsatellite instability. Multiple pathways have been identified, regulated by many positive and negative factors involved in the development of cancer, which in this case follows the ‘inflammation-dysplasia-carcinoma’ sequence. Strategies to lower this risk are extremely important to reduce morbidity and mortality due to IBD-CRC, among which colonoscopic surveillance is the most widely accepted and implemented modality, forming part of many national and international guidelines. However, the effectiveness of surveillance in IBD has been a topic of much debate in recent years for multiple reasons — cost-benefit to health systems, resource requirements, and also because of studies showing conflicting long-term data. Our review provides a comprehensive overview of past, present, and future perspectives of IBD-CRC. We explore and analyse evidence from studies over decades and current best practices followed globally. In the future directions section, we cover emerging novel endoscopic techniques and artificial intelligence that could play an important role in managing the risk of IBD-CRC.
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Affiliation(s)
- Snehali Majumder
- Department of Clinical Research, Narayana Health, Bangalore 560099, Karnataka, India
| | - Uday Nagesh Shivaji
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, United Kingdom
| | - Rangarajan Kasturi
- Department of Gastroenterology, Narayana Health, Bangalore 560099, India
| | - Alben Sigamani
- Department of Clinical Research, Narayana Health, Bangalore 560099, Karnataka, India
| | - Subrata Ghosh
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, United Kingdom
| | - Marietta Iacucci
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, United Kingdom
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Damião AOMC, Queiroz NSF. Medical Therapy in Chronic Refractory Ulcerative Colitis: When Enough Is Enough. Clin Colon Rectal Surg 2022; 35:32-43. [PMID: 35069028 PMCID: PMC8763462 DOI: 10.1055/s-0041-1740036] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Despite significant improvements in the management of ulcerative colitis (UC) in parallel with the evolution of therapeutic targets and novel biologics and small molecules, a subset of medically refractory patients still requires colectomy. Recent population-based studies demonstrate a trend toward a decrease in the rates of surgery for UC patients in the biological era, although the potential of disease modification with these agents is still debated. As the concept of irreversible bowel damage is underexplored in UC, refractory patients can be exposed to multiple treatments losing optimal timing for surgery and further developing complications such as dysplasia/cancer, dysmotility, microcolon, and other functional abnormalities. This review aims to discuss the concept of disease progression in UC, explore the limitations of medical treatment in refractory UC patients, and propose the application of a three-step algorithm that allows timely indication for surgery in clinical practice.
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Affiliation(s)
| | - Natália Sousa Freitas Queiroz
- Department of Gastroenterology, University of São Paulo School of Medicine, São Paulo, Brazil,Address for correspondence Natália Sousa Freitas Queiroz, MD, PhD Department of Gastroenterology, University of São Paulo School of MedicineSão Paulo 05403-000Brazil
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Vitello A, Shahini E, Macaluso FS, Morreale GC, Sinagra E, Pallio S, Maida M. Endoscopic surveillance of colorectal cancer in inflammatory bowel diseases: a review of the literature. Expert Rev Anticancer Ther 2020; 20:851-863. [PMID: 32811225 DOI: 10.1080/14737140.2020.1813030] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/26/2020] [Accepted: 08/18/2020] [Indexed: 02/08/2023]
Abstract
INTRODUCTION The risk of colorectal cancer (CRC) in patients with inflammatory bowel diseases (IBD) is higher compared to the general population and it is related to the type, severity, duration, and extension of the disease. AREAS COVERED This review aims to highlight current evidence from the literature supporting the role of endoscopic surveillance of CRC in patients with IBD. EXPERT OPINION Even in the absence of randomized controlled trials (RCTs), evidence from the literature supports the effectiveness of endoscopic surveillance in reducing IBD-related CRC incidence and mortality. As a consequence, current guidelines recommend colonoscopy 8-10 years after disease or symptom onset in all patients with ulcerative colitis (UC) and Crohn's disease (CD) involving at least one-third of the colon and agree on the necessity of annual surveillance in high-risk patients. Nevertheless, an overall agreement on the optimal intervals for surveillance of low-intermediate risk patients is absent and 2-5 year intervals have been proposed. In the near future, further studies are needed to assess the most effective intervals and tailor the surveillance based on the personal risk profile. Additionally, further efforts should be made to evaluate the role of noninvasive tests as primary screening, thus avoiding unnecessary colonoscopies.
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Affiliation(s)
- Alessandro Vitello
- Gastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital , Caltanissetta, Italy
| | - Endrit Shahini
- Diagnostic and Interventional Endoscopy, Candiolo Cancer Institute, FPO - IRCCS - Candiolo , Torino, Italy
| | - Fabio S Macaluso
- Internal Medicine, Villa Sofia - V. Cervello Hospital , Palermo, Italy
| | - Gaetano C Morreale
- Gastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital , Caltanissetta, Italy
| | - Emanuele Sinagra
- Gastroenterology and Endoscopy Unit, Istituto San Raffaele Giglio , Cefalù, Italy
| | - Socrate Pallio
- Digestive Diseases Endoscopy Unit, Policlinico G. Martino Hospital, University of Messina , Messina, Italy
| | - Marcello Maida
- Gastroenterology and Endoscopy Unit, S. Elia-Raimondi Hospital , Caltanissetta, Italy
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Zhou Q, Shen ZF, Wu BS, Xu CB, He ZQ, Chen T, Shang HT, Xie CF, Huang SY, Chen YG, Chen HB, Han ST. Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract 2019; 2019:5363261. [PMID: 31781191 PMCID: PMC6874962 DOI: 10.1155/2019/5363261] [Citation(s) in RCA: 56] [Impact Index Per Article: 9.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2019] [Accepted: 08/22/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Ulcerative colitis (UC) patients have an increased risk for the development of colorectal cancer (CRC). Our aim was to assess the risk of CRC in UC patients compared with disease extent, disease duration, and geographic variation. METHODS In this systematic review and meta-analysis, we searched PubMed, scientific meetings, and the bibliographies of identified articles, with English language restrictions for studies published from 1988 to 2018, and assessed the risk of CRC in UC patients. Patients with Crohn's disease, family history of CRC, and colorectal adenomatous polyp (CAP) were excluded from this research. The study was registered with PROSPERO, number CRD42018102213. FINDINGS We included 58 studies that included 267566 UC patients. Extensive UC and left-sided UC had a higher risk of CRC than proctitis UC. Geography also played a role in UC-associated CRC development. The time of malignant transformation in Asian UC patients started after 10-20 years of this disease duration. North American UC-associated CRC patients significantly increased in more than 30 years of this disease duration. CONCLUSION In a systematic review of the literature, we found that disease extent, disease duration, and geography were strong, independent risk factors in UC-associated CRC development.
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Affiliation(s)
- Qing Zhou
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Zhao-Feng Shen
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Ben-sheng Wu
- Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu, China
| | - Cheng-biao Xu
- Xuyi Hospital of Traditional Chinese Medicine, Huaian, Jiangsu, China
| | - Zhong-qi He
- Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu, China
| | - Tuo Chen
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Hong-tao Shang
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Chao-fan Xie
- Shishi General Hospital, Quanzhou, Fujian, China
| | - Si-yi Huang
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Yu-gen Chen
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Hai-bo Chen
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Shu-tang Han
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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9
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Mortality Risk of Inflammatory Bowel Disease: A Case-Control Study of New York State Death Records. Dig Dis Sci 2019; 64:1604-1611. [PMID: 30604370 DOI: 10.1007/s10620-018-5430-8] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2018] [Accepted: 12/12/2018] [Indexed: 01/16/2023]
Abstract
BACKGROUND Studies examining the mortality risk of inflammatory bowel disease (IBD) have yielded conflicting results, and most do not account for recent advancements made in the treatment of Crohn's disease (CD) and ulcerative colitis (UC). We aim to assess the overall, premature, and cause-specific mortality in IBD patients over a 17-year time period and to evaluate any differences since the introduction of biologic therapy. METHODS A death record case-control study was performed to explore the odds of premature death (before age 65) and all-cause mortality among those with IBD. Cases consisted of IBD patients (1,129 with CD and 841 with UC) who died in New York State (NYS) from 1993 to 2010. Controls (n = 7880) were matched 4:1 on the basis of sex and zip code from those who died in NYS in the same time frame, without an IBD diagnosis. RESULTS Compared with matched controls, those with CD (OR 1.56, CI 95% 1.34-1.82), but not UC (OR 0.72, CI 95% 0.59-0.89), were more likely to die prematurely. Both those with UC and CD were more likely to die from a gastrointestinal cause (CD OR 15.28, 95% CI 12.11-19.27; UC OR 14.02, 95% CI 10.76-18.26). There was no difference in the cause or age of death before and after the introduction of anti-TNF agents in those with IBD. CONCLUSIONS Both CD and UC cases were more likely to die of a gastrointestinal etiology, and CD patients were more likely to die prematurely. There was no significant difference in the premature death, average age of death, and cause of death in this IBD population after the availability of anti-TNF therapy.
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Fumery M, Singh S, Dulai PS, Gower-Rousseau C, Peyrin-Biroulet L, Sandborn WJ. Natural History of Adult Ulcerative Colitis in Population-based Cohorts: A Systematic Review. Clin Gastroenterol Hepatol 2018; 16. [PMID: 28625817 PMCID: PMC6658168 DOI: 10.1016/j.cgh.2017.06.016] [Citation(s) in RCA: 306] [Impact Index Per Article: 43.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS A comprehensive knowledge of the natural history of ulcerative colitis (UC) helps understand disease evolution, identify poor prognostic markers and impact of treatment strategies, and facilitates shared decision-making. We systematically reviewed the natural history of UC in adult population-based cohort studies with long-term follow-up. METHODS Through a systematic literature review of MEDLINE through March 31, 2016, we identified 60 studies performed in 17 population-based inception cohorts reporting the long-term course and outcomes of adult-onset UC (n = 15,316 UC patients). RESULTS Left-sided colitis is the most frequent location, and disease extension is observed in 10%-30% of patients. Majority of patients have a mild-moderate course, which is most active at diagnosis and then in varying periods of remission or mild activity; about 10%-15% of patients experience an aggressive course, and the cumulative risk of relapse is 70%-80% at 10 years. Almost 50% of patients require UC-related hospitalization, and 5-year risk of re-hospitalization is ∼50%. The 5-year and 10-year cumulative risk of colectomy is 10%-15%; achieving mucosal healing is associated with lower risk of colectomy. About 50% of patients receive corticosteroids, although this proportion has decreased over time, with a corresponding increase in the use of immunomodulators (20%) and anti-tumor necrosis factor (5%-10%). Although UC is not associated with an increased risk of mortality, it is associated with high morbidity and work disability, comparable to Crohn's disease. CONCLUSIONS UC is a disabling condition over time. Prospective cohorts are needed to evaluate the impact of recent strategies of early use of disease-modifying therapies and treat-to-target approach with immunomodulators and biologics. Long-term studies from low-incidence areas are also needed.
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Affiliation(s)
- Mathurin Fumery
- Division of Gastroenterology, University of California San Diego, La Jolla, California; Gastroenterology Unit, Epimad Registry, Amiens University Hospital, Amiens, France.
| | - Siddharth Singh
- Division of Gastroenterology, University of California San Diego, La Jolla, California;,Division of Biomedical Informatics, University of California San Diego, La Jolla, California
| | - Parambir S. Dulai
- Division of Gastroenterology, University of California San Diego, La Jolla, California
| | - Corinne Gower-Rousseau
- LIRIC Inserm, Unit 995, Lille University, France; Epidemiology Unit, Epimad egistry, Lille University Hospital, France
| | | | - William J. Sandborn
- Division of Gastroenterology, University of California San Diego, La Jolla, California
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Kisiel JB, Konijeti GG, Piscitello AJ, Chandra T, Goss TF, Ahlquist DA, Farraye FA, Ananthakrishnan AN. Stool DNA Analysis is Cost-Effective for Colorectal Cancer Surveillance in Patients With Ulcerative Colitis. Clin Gastroenterol Hepatol 2016; 14:1778-1787.e8. [PMID: 27464589 PMCID: PMC5108686 DOI: 10.1016/j.cgh.2016.07.018] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2016] [Revised: 06/17/2016] [Accepted: 07/10/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with chronic ulcerative colitis are at increased risk for colorectal neoplasia (CRN). Surveillance by white-light endoscopy (WLE) or chromoendoscopy may reduce risk of CRN, but these strategies are underused. Analysis of DNA from stool samples (sDNA) can detect CRN with high levels of sensitivity, but it is not clear if this approach is cost-effective. We simulated these strategies for CRN detection to determine which approach is most cost-effective. METHODS We adapted a previously published Markov model to simulate the clinical course of chronic ulcerative colitis, the incidence of cancer or dysplasia, and costs and benefits of care with 4 surveillance strategies: (1) analysis of sDNA and diagnostic chromoendoscopy for patients with positive results, (2) analysis of sDNA with diagnostic WLE for patients with positive results, (3) chromoendoscopy with targeted collection of biopsies, or (4) WLE with random collection of biopsies. Costs were based on 2014 Medicare reimbursement. The primary outcome was the incremental cost-effectiveness ratio (incremental cost/incremental difference in quality-adjusted life-years) compared with no surveillance and a willingness-to-pay threshold of $50,000. RESULTS All strategies fell below the willingness-to-pay threshold at 2-year intervals. Incremental cost-effectiveness ratios were $16,362 per quality-adjusted life-year for sDNA analysis with diagnostic chromoendoscopy; $18,643 per quality-adjusted life-year for sDNA analysis with diagnostic WLE; $23,830 per quality-adjusted life-year for chromoendoscopy alone; and $27,907 per quality-adjusted life-year for WLE alone. In sensitivity analyses, sDNA analysis with diagnostic chromoendoscopy was more cost-effective than chromoendoscopy alone, up to a cost of $1135 per sDNA test. sDNA analysis remained cost-effective at all rates of compliance; when combined with diagnostic chromoendoscopy, this approach was preferred over chromoendoscopy alone, when the specificity of the sDNA test for CRN was >65%. CONCLUSIONS Based on a Markov model, surveillance for CRN is cost-effective for patients with chronic ulcerative colitis. Analysis of sDNA with chromoendoscopies for patients with positive results was more cost-effective than chromoendoscopy or WLE alone.
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Affiliation(s)
- John B. Kisiel
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester MN
| | - Gauree G. Konijeti
- Division of Gastroenterology, Scripps Clinic, La Jolla CA,Scripps Translational Science Institute, La Jolla, CA
| | | | | | | | - David A. Ahlquist
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester MN
| | - Francis A. Farraye
- Center for Digestive Disorders, Boston Medical Center, Section of Gastroenterology, Boston University School of Medicine, Boston MA
| | - Ashwin N. Ananthakrishnan
- Division of Gastroenterology and Hepatology, Massachusetts General Hospital and Harvard Medical School, Boston MA
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12
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Yoshino T, Nakase H, Takagi T, Bamba S, Okuyama Y, Kawamura T, Oki T, Obata H, Kawanami C, Katsushima S, Kusaka T, Tsujikawa T, Naito Y, Andoh A, Kogawa T. Risk factors for developing colorectal cancer in Japanese patients with ulcerative colitis: a retrospective observational study-CAPITAL (Cohort and Practice for IBD total management in Kyoto-Shiga Links) study I. BMJ Open Gastroenterol 2016; 3:e000122. [PMID: 27933204 PMCID: PMC5128829 DOI: 10.1136/bmjgast-2016-000122] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/12/2016] [Revised: 10/15/2016] [Accepted: 10/23/2016] [Indexed: 12/30/2022] Open
Abstract
Background and Aims Patients with ulcerative colitis (UC) are at risk for developing colorectal cancer (CRC), despite the development of new therapeutic agents. Stratification of the individual UC-patient's risk would be helpful to validate the risk factors for CRC. The aim of this study was to evaluate the risk factors for the development of CRC in a large cohort of patients with UC. Methods Data were obtained from 12 hospitals in the Kyoto-Shiga region during 2003–2013. We performed a retrospective cohort study of 2137 patients with UC. Results In total, 60 lesions of CRC were detected in 43 (2.0%) of 2137 patients. 30 of the 43 patients were male. The median age was 53 years. The median duration of disease was 13 years, and 67.4% of these patients had a disease duration >10 years. Of the 43 patients, 34 (79.1%) had extensive colitis. Primary sclerosing cholangitis was detected in 2 patients (4.7%). The median corticosteroids (CS) dose was 6.4 g, and 4 patients were treated with a total of more than 10 g of CS. 18 of these patients underwent more than 1 year CS treatment. Of all 60 CRC lesions, 43 (71.7%) were located in the distal colon and 35 (58.3%) were of the superficial type. Moreover, the stage of CRC was stage 0 or I in 55.8% of the 43 patients with CRC. Multivariate analysis suggested that extensive colitis could be a risk factor for the development of advanced CRC in patients with UC. Conclusions Our findings indicated that male, extensive colitis, long-term duration of UC and family history of CRC, but not concomitant primary sclerosing cholangitis, are important factors for predicting CRC in Japanese patients with UC. Moreover, long-standing extensive colitis might contribute to the progression of CRC. Further studies are required to establish CRC surveillance in Japanese patients with UC.
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Affiliation(s)
- Takuya Yoshino
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Division of Gastroenterology and Hepatology, Digestive Disease Center, Kitano Hospital, Osaka, Japan
| | - Hiroshi Nakase
- Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan; Department of Gastroenterology & Hepatology, Sapporo Medical University School of Medicine, Sapporo, Japan
| | - Tomohisa Takagi
- Molecular Gastroenterology and Hepatology , Kyoto Prefectural University of Medicine, Graduate School of Medical Science , Kyoto , Japan
| | - Shigeki Bamba
- Division of Gastroenterology , Shiga University of Medical Science Hospital , Otsu , Japan
| | - Yusuke Okuyama
- Department of Gastroenterology and Hepatology , Japanese Red Cross Kyoto Daiichi Hospital , Kyoto , Japan
| | - Takuji Kawamura
- Department of Gastroenterology , Kyoto Second Red Cross Hospital , Kyoto , Japan
| | | | | | - Chiharu Kawanami
- Department of Gastroenterology and Hepatology , Japanese Red Cross Otsu Hospital , Otsu , Japan
| | - Shinji Katsushima
- Department of Gastroenterology and Hepatology , National Hospital Organization, Kyoto Medical Center , Kyoto , Japan
| | - Toshihiro Kusaka
- Division of Gastroenterology and Hepatology , Digestive Disease Center, Kyoto Katsura Hospital , Kyoto , Japan
| | - Tomoyuki Tsujikawa
- Department of Gastroenterology and Hepatology , National Hospital Organization, Higashi-Ohmi Medical Center , Higashi-Ohmi , Japan
| | - Yuji Naito
- Molecular Gastroenterology and Hepatology , Kyoto Prefectural University of Medicine, Graduate School of Medical Science , Kyoto , Japan
| | - Akira Andoh
- Division of Gastroenterology , Shiga University of Medical Science Hospital , Otsu , Japan
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13
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Parian A, Lazarev M. Who and how to screen for cancer in at-risk inflammatory bowel disease patients. Expert Rev Gastroenterol Hepatol 2015; 9:731-46. [PMID: 25592672 DOI: 10.1586/17474124.2015.1003208] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Inflammatory bowel diseases (IBDs) include both Crohn's disease and ulcerative colitis and both diseases are marked by inflammation within the gastrointestinal tract. Due to long-standing inflammation, IBD patients are at increased risk of colorectal cancer, especially patients with chronic inflammation, pancolitis, co-diagnosis of primary sclerosing cholangitis and a longer duration of disease. Small bowel inflammation places Crohn's patients at an increased risk of small bowel cancer. A higher risk of skin cancers, lymphomas and cervical abnormalities is also seen in IBD patients; this is likely related to both disease factors and the presence of immunosuppressive medication. This article reviews which patients are at an increased risk of IBD-associated or IBD treatment-associated cancers, when to begin screening and which screening methods are recommended.
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Affiliation(s)
- Alyssa Parian
- Department of Gastroenterology, Johns Hopkins University, 4940 Eastern Avenue, Building A, Baltimore, MD 21224, USA
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14
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Desai D, Shah S, Deshmukh A, Abraham P, Joshi A, Gupta T, Deshpande R, Khandagale V, George S. Colorectal cancers in ulcerative colitis from a low-prevalence area for colon cancer. World J Gastroenterol 2015; 21:3644-3649. [PMID: 25834332 PMCID: PMC4375589 DOI: 10.3748/wjg.v21.i12.3644] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2014] [Revised: 10/11/2014] [Accepted: 01/08/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine the incidence and risk factors for colorectal cancer (CRC) in patients with ulcerative colitis from a low prevalence region for CRC.
METHODS: Our prospective database yielded a cohort of 430 patients [age: 44 ± 14.6 years; 248 men (57.7%)] with ulcerative colitis (median disease duration 6, range: 1-39 years) for analysis. Of these, 131 (30.5%) had left-sided colitis and 159 (37%) extensive colitis. Patients with histologically confirmed CRC within the segment with colitis were compared with those without CRC, to determine the risk factors for the development of CRC.
RESULTS: Twelve patients (2.8%) developed CRC. The overall incidence density was 3.56/1000 patient-years of disease - 3/1000 in the first 10 years, 3.3/1000 at 10 to 20 years, and 7/1000 at > 20 years. Three of our 12 patients developed CRC within 8 years of disease onset. On univariate analysis, extensive colitis, longer duration of disease, and poor control of disease were associated with development of CRC. On multivariate analysis, duration of disease and extent of colitis remained significant.
CONCLUSION: CRC occurred in 2.8% of patients with ulcerative colitis in our population - an incidence density similar to that in Western countries in spite of a low overall prevalence of colon cancer in our population. The risk increased with extent and duration of disease.
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15
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Abstract
Patients with inflammatory bowel diseases (IBDs) are at increased risk of colorectal cancer (CRC), but the risk varies between different studies and seems to be decreasing. The cumulative risk of CRC has been reported to be 1%, 2%, and 5% after 10, 20, and over 20 years of disease duration, respectively, in recent meta-analysis. Disease duration and grade of inflammation are the main driving forces of dysplasia and CRC development. Also, the risk of extraintestinal cancers is increased in IBD, where the degree of immunosuppression and its duration are the most important risk factors. Most important extraintestinal malignancies are lymphomas and non-melanoma skin cancers, both of which are increased in patients receiving thiopurines. Also, extraintestinal manifestations or concomitant diseases such as primary sclerosing cholangitis predispose IBD patients to malignancies such as cholangiocarcinoma. History of previous cancer increases the risk of developing either new or recurrent cancers and should be taken into account when choosing therapy and planning surveillance. Dysplasia and cancer screening and surveillance must be individualized according to patients' risk factors. Malignancies are the second most common cause of death after cardiovascular diseases in both genders in patients with IBD.
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Affiliation(s)
- Urpo Nieminen
- Helsinki University Hospital, Department of Medicine, Division of Gastroenterology , Helsinki , Finland
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16
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Mortality and causes of death in patients with inflammatory bowel disease: a nationwide register study in Finland. J Crohns Colitis 2014; 8:1088-96. [PMID: 24630486 DOI: 10.1016/j.crohns.2014.02.015] [Citation(s) in RCA: 57] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/05/2013] [Revised: 01/29/2014] [Accepted: 02/13/2014] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIM Increased mortality has been reported in Crohn's disease (CD) but mostly not in ulcerative colitis (UC). We evaluated the overall and cause-specific mortality in a nationwide cohort of patients with inflammatory bowel disease (IBD) in Finland. METHODS A total of 21,964 patients with IBD (16,649 with UC and 5315 with CD) from the Special Reimbursement register were diagnosed 1987-1993 and 2000-2007 and followed up to the end of 2010 by collating these figures with the national computerized Cause-of-Death Register of Statistics Finland. In each cause-of-death category, the number of deaths reported was compared to that expected in general population, and expressed as a standardized mortality ratio (SMR). RESULTS Overall mortality was increased among patients with CD (SMR 1.33, 95% confidence interval 1.21-1.46) and UC (1.10, 1.05-1.15). SMR was significantly increased for gastrointestinal causes in CD (6.53, 4.91-8.52) and UC (2.81, 2.32-3.34). Patients with UC were found also to have increased SMR from pulmonary (1.24, 1.02-1.46) and cardiovascular disease (1.14, 1.06-1.22) and cancers of the colon (1.90, 1.38-2.55), rectum (1.79, 1.14-2.69) and biliary tract (5.65, 3.54-8.54), whereas SMR from alcohol-related deaths was decreased (0.54, 0.39-0.71). Patients with CD had a significantly increased SMR for pulmonary diseases (2.01, 1.39-2.80), infections (4.27, 2.13-7.63) and cancers of the biliary tract (4.51, 1.23-11.5) and lymphoid and hematopoietic tissue (2.95, 1.85-4.45). CONCLUSIONS In this Finnish nationwide study increased overall mortality in both CD and UC was observed. The excess mortality of 14% in IBD is mainly due to deaths related to inflammation in the gut.
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Castaño-Milla C, Chaparro M, Gisbert JP. Systematic review with meta-analysis: the declining risk of colorectal cancer in ulcerative colitis. Aliment Pharmacol Ther 2014; 39:645-59. [PMID: 24612141 DOI: 10.1111/apt.12651] [Citation(s) in RCA: 197] [Impact Index Per Article: 17.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/20/2013] [Revised: 07/19/2013] [Accepted: 01/18/2014] [Indexed: 12/13/2022]
Abstract
BACKGROUND Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC); however, the magnitude of this effect is open to debate. AIM To assess the risk of CRC in UC patients by systematic review and meta-analysis. METHODS A systematic literature search was performed up to November 2013. We selected studies describing the incidence and prevalence of CRC in patients with UC. Articles were assessed for quality using the Newcastle-Ottawa Scale. Cumulative incidence and incidence rates of CRC were combined and analysed using the generic inverse variance method. Sub-analyses were performed to identify factors associated with an increased risk of developing CRC. RESULTS A total of 81 studies (181 923 patients) met the inclusion criteria. The incidence rate of CRC in patients with UC was 1.58 per 1000 patient-years (py) [95% confidence interval (CI), 1.39–1.76]. Results were heterogeneous (I2 = 81–89%). The incidence rate was 4.02/1000 py (95%CI = 2.74–5.31) in studies that only included patients with extensive colitis, and 1.24/1000 py (95%CI = 1.01–1.47) in population-based studies. The incidence rate was 0.91/1000 py (95%CI = 0.61–1.2) in the first decade of disease, 4.07/1000 py (95%CI = 2.58–5.56) in the second, and 4.55/1000 py (95%CI = 2.64–6.46) in the third. The incidence rate decreased from 4.29/1000 py in the studies published in the 1950s to 1.21/1000 py in studies published in the last decade. CONCLUSIONS The risk of patients with ulcerative colitis developing colorectal cancer has decreased steadily over the last six decades, but the extent and duration of the disease increase this risk.
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18
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Sebastian S, Hernández V, Myrelid P, Kariv R, Tsianos E, Toruner M, Marti-Gallostra M, Spinelli A, van der Meulen-de Jong AE, Yuksel ES, Gasche C, Ardizzone S, Danese S. Colorectal cancer in inflammatory bowel disease: results of the 3rd ECCO pathogenesis scientific workshop (I). J Crohns Colitis 2014; 8:5-18. [PMID: 23664897 DOI: 10.1016/j.crohns.2013.04.008] [Citation(s) in RCA: 99] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2013] [Accepted: 04/05/2013] [Indexed: 02/08/2023]
Abstract
Epidemiological studies demonstrate an increased risk of colorectal cancer in patients with inflammatory bowel disease (IBD). A detailed literature review was conducted on epidemiology, risk factors, pathophysiology, chemoprevention and outcomes of colorectal cancer (CRC) in IBD as part of the 3rd ECCO scientific pathogenesis workshop.
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Affiliation(s)
- Shaji Sebastian
- Hull & East Yorkshire Hospitals NHS Trust, Hull York Medical School, Hull, United Kingdom.
| | - Vincent Hernández
- Gastroenterology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain
| | - Pär Myrelid
- Division of Surgery, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, County Council of Östergötland, Linköping, Sweden
| | - Revital Kariv
- Service for Gastrointestinal Malignancies, Department of Gastroenterology & Liver Disease, Tel Aviv Sourasky Medical Center, Israel
| | - Epameinondas Tsianos
- University of Ioannina, 1st Division of Internal Medicine and Hepato-Gastroenterology Unit, Greece
| | - Murat Toruner
- Ankara University Medical School, Ibni Sina Hospital, Division of Gastroenterology, Ankara, Turkey
| | - Marc Marti-Gallostra
- Department of Colorectal Surgery, University Hospital of Valle de Hebron, Barcelona, Spain
| | - Antonino Spinelli
- Dipartimento e Cattedra di Chirurgia Generale, Istituto Clinico Humanitas IRCCS, Università degli Studi di Milano, Rozzano, Milano, Italy
| | | | - Elif Sarıtas Yuksel
- Department of Gastroenterology, Katip Celebi University, Ataturk Research and Teaching Hospital, Izmir, Turkey
| | - Christoph Gasche
- Christian Doppler Laboratory on Molecular Cancer Chemoprevention, Division of Gastroenterology, Medical University of Vienna, Vienna, Austria
| | - Sandro Ardizzone
- Chair of Gastroenterology, "L. Sacco" University Hospital, Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology, Istituto Clinico Humanitas, Milan, Italy.
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Abstract
BACKGROUND Data from the northern hemisphere suggest that patients with ulcerative colitis (UC) have similar survival to the general population, whereas mortality in Crohn's disease (CD) is increased by up to 50%. There is a paucity of data from the southern hemisphere, especially in Australia. METHODS A prevalence cohort (1977-1992) of patients with inflammatory bowel disease (IBD) diagnosed after 1970 was studied. Survival status data and causes of death up to December 2010 were extracted from the National Death Index. Relative survival analysis was carried out separately for men and women. RESULTS Of 816 cases (384 men, 432 women; 373 CD, 401 UC, 42 indeterminate colitis), 211 (25.9%) had died by December 2010. Median follow-up was 22.2 years. Relative survival of all patients with IBD was not significantly different from the general population at 10, 20, and 30 years of follow-up. Separate analyses of survival in CD and UC also showed no differences from the general population. There was no difference in survival between patients diagnosed earlier (1971-1979) or later (1980-1992). At least 17% of the deaths were caused by IBD. Fatal cholangiocarcinomas were more common in IBD (P < 0.001), and fatal colorectal cancers more common in UC (P = 0.047). CONCLUSIONS In Australia, IBD patient survival is similar to the general population. In contrast to data from Europe and North America, survival in CD is not diminished in Australia. IBD caused direct mortality in 17%, especially as biliary and colorectal cancers are significant causes of death.
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Meta-analyses of colorectal cancer risk factors. Cancer Causes Control 2013; 24:1207-22. [PMID: 23563998 DOI: 10.1007/s10552-013-0201-5] [Citation(s) in RCA: 515] [Impact Index Per Article: 42.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/23/2012] [Accepted: 03/26/2013] [Indexed: 02/06/2023]
Abstract
PURPOSE Demographic, behavioral, and environmental factors have been associated with increased risk of colorectal cancer (CRC). We reviewed the published evidence and explored associations between risk factors and CRC incidence. METHODS We identified 12 established non-screening CRC risk factors and performed a comprehensive review and meta-analyses to quantify each factor's impact on CRC risk. We used random-effects models of the logarithms of risks across studies: inverse-variance weighted averages for dichotomous factors and generalized least squares for dose-response for multi-level factors. RESULTS Significant risk factors include inflammatory bowel disease (RR = 2.93, 95 % CI 1.79-4.81); CRC history in first-degree relative (RR = 1.80, 95 % CI 1.61-2.02); body mass index (BMI) to overall population (RR = 1.10 per 8 kg/m(2) increase, 95 % CI 1.08-1.12); physical activity (RR = 0.88, 95 % CI 0.86-0.91 for 2 standard deviations increased physical activity score); cigarette smoking (RR = 1.06, 95 % CI 1.03-1.08 for 5 pack-years); and consumption of red meat (RR = 1.13, 95 % CI 1.09-1.16 for 5 servings/week), fruit (RR = 0.85, 95 % CI 0.75-0.96 for 3 servings/day), and vegetables (RR = 0.86, 95 % CI 0.78-0.94 for 5 servings/day). CONCLUSIONS We developed a comprehensive risk modeling strategy that incorporates multiple effects to predict an individual's risk of developing CRC. Inflammatory bowel disease and history of CRC in first-degree relatives are associated with much higher risk of CRC. Increased BMI, red meat intake, cigarette smoking, low physical activity, low vegetable consumption, and low fruit consumption were associated with moderately increased risk of CRC.
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Crohn's disease and ulcerative colitis are associated with elevated standardized mortality ratios: a meta-analysis. Inflamm Bowel Dis 2013; 19:599-613. [PMID: 23388544 PMCID: PMC3755276 DOI: 10.1097/mib.0b013e31827f27ae] [Citation(s) in RCA: 109] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Evidence regarding all-cause and cause-specific mortality in inflammatory bowel disease (IBD) is conflicting, and debate exists over appropriate study design to examine these important outcomes. We conducted a comprehensive meta-analysis of all-cause and cause-specific mortality in both Crohn's disease (CD) and ulcerative colitis (UC), and additionally examined various effects of study design on this outcome. METHODS A systematic search of PubMed and EMBASE was conducted to identify studies examining mortality rates relative to the general population. Pooled summary standardized mortality ratios (SMR) were calculated using random effect models. RESULTS Overall, 35 original articles fulfilled the inclusion and exclusion criteria, reporting all-cause mortality SMRs varying from 0.44 to 7.14 for UC and 0.71 to 3.20 for CD. The all-cause mortality summary SMR for inception cohort and population cohort UC studies was 1.19 (95% confidence interval, 1.06-1.35). The all-cause mortality summary SMR for inception cohort and population cohort CD studies was 1.38 (95% confidence interval, 1.23-1.55). Mortality from colorectal cancer, pulmonary disease, and nonalcoholic liver disease was increased, whereas mortality from cardiovascular disease was decreased. CONCLUSIONS Patients with UC and CD have higher rates of death from all causes, colorectal-cancer, pulmonary disease, and nonalcoholic liver disease.
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Declining risk of colorectal cancer in inflammatory bowel disease: an updated meta-analysis of population-based cohort studies. Inflamm Bowel Dis 2013; 19:789-99. [PMID: 23448792 DOI: 10.1097/mib.0b013e31828029c0] [Citation(s) in RCA: 374] [Impact Index Per Article: 31.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND Recently reported risks of colorectal cancer (CRC) in inflammatory bowel disease (IBD) have been lower than those reported before 2000. The aim of this meta-analysis was to update the CRC risk of ulcerative and Crohn's colitis, investigate time trends, and identify high-risk modifiers. METHODS The MEDLINE search engine was used to identify all published cohort studies on CRC risk in IBD. Publications were critically appraised for study population, Crohn's disease localization, censoring for colectomy, and patient inclusion methods. The following data were extracted: total and stratified person-years at risk, number of observed CRC, number of expected CRC in background population, time period of inclusion, and geographical location. Pooled standardized incidence ratios and cumulative risks for 10-year disease intervals were calculated. Results were corrected for colectomy and isolated small bowel Crohn's disease. RESULTS The pooled standardized incidence ratio of CRC in all patients with IBD in population-based studies was 1.7 (95% confidence interval [CI], 1.2-2.2 ). High-risk groups were patients with extensive colitis and an IBD diagnosis before age 30 with standardized incidence ratios of 6.4 (95% confidence interval, 2.4-17.5) and 7.2 (95% confidence interval, 2.9-17.8), respectively. Cumulative risks of CRC were 1%, 2%, and 5% after 10, 20, and >20 years of disease duration, respectively. CONCLUSIONS The risk of CRC is increased in patients with IBD but not as high as previously reported and not in all patients. This decline could be the result of aged cohorts. The risk of CRC is significantly higher in patients with longer disease duration, extensive disease, and IBD diagnosis at young age.
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Selinger CP, Leong RW. Mortality from inflammatory bowel diseases. Inflamm Bowel Dis 2012; 18:1566-72. [PMID: 22275300 DOI: 10.1002/ibd.22871] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/27/2011] [Accepted: 12/11/2011] [Indexed: 12/11/2022]
Abstract
Ulcerative colitis (UC) and Crohn's disease (CD) may directly result in morbidity and rarely mortality from complications such as colorectal cancer or sepsis. Mortality rates compared with the matched general population, measured by standardized mortality ratio, may therefore be increased. This review examines the evidence derived from cohort- and population-based mortality studies. In CD the majority of studies and two meta-analyses demonstrated increased standardized mortality ratios of ≈ 1.5-fold, especially for those diagnosed at younger ages and requiring extensive or multiple resection surgery. In UC mortality rates are similar to those of the general population in most studies and a meta-analysis. Proctocolectomy removes the inflammatory burden of UC and can manage colorectal dysplasia but may result in perioperative complications. There is no clear temporal trend of improvement in survival for either CD or UC. Few data are available from countries outside Europe and North America, so geographical influences remain largely unknown.
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Affiliation(s)
- Christian P Selinger
- Gastroenterology and Liver Services, Sydney Local Health Service, Concord Repatriation General Hospital, Sydney, New South Wales, Australia
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Jess T, Rungoe C, Peyrin-Biroulet L. Risk of colorectal cancer in patients with ulcerative colitis: a meta-analysis of population-based cohort studies. Clin Gastroenterol Hepatol 2012; 10:639-45. [PMID: 22289873 DOI: 10.1016/j.cgh.2012.01.010] [Citation(s) in RCA: 655] [Impact Index Per Article: 50.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/23/2011] [Accepted: 01/15/2012] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with ulcerative colitis (UC) have an increased risk of developing colorectal cancer (CRC). Studies examining the magnitude of this association have yielded conflicting results. We performed a meta-analysis of population-based cohort studies to determine the risk of CRC in patients with UC. METHODS We used MEDLINE, EMBASE, Cochrane, and CINAHL to perform a systematic literature search. We included 8 studies in the meta-analysis on the basis of strict inclusion and exclusion criteria. We calculated pooled standardized incidence ratios (SIRs) with 95% confidence intervals (CIs) for risk of CRC in patients with UC and performed meta-regression analyses of the effect of cohort size, calendar period, observation time, percentage with proctitis, and rates of colectomy on the risk of CRC. RESULTS An average of 1.6% of patients with UC was diagnosed with CRC during 14 years of follow-up. SIRs ranged from 1.05 to 3.1, with a pooled SIR of 2.4 (95% CI, 2.1-2.7). Men with UC had a greater risk of CRC (SIR, 2.6; 95% CI, 2.2-3.0) than women (SIR, 1.9; 95% CI, 1.5-2.3). Young age was a risk factor for CRC (SIR, 8.6; 95% CI, 3.8-19.5; although this might have resulted from small numbers), as was extensive colitis (SIR, 4.8; 95% CI, 3.9-5.9). In meta-regression analyses, only cohort size was associated with risk of CRC. CONCLUSIONS In population-based cohorts, UC increases the risk of CRC 2.4-fold. Male sex, young age at diagnosis with UC, and extensive colitis increase the risk.
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Affiliation(s)
- Tine Jess
- Department of Epidemiology Research, Statens Serum Institut, Copenhagen, Denmark.
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Miehsler W, Novacek G, Wenzl H, Vogelsang H, Knoflach P, Kaser A, Dejaco C, Petritsch W, Kapitan M, Maier H, Graninger W, Tilg H, Reinisch W. A decade of infliximab: The Austrian evidence based consensus on the safe use of infliximab in inflammatory bowel disease. J Crohns Colitis 2010; 4:221-56. [PMID: 21122513 DOI: 10.1016/j.crohns.2009.12.001] [Citation(s) in RCA: 72] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/20/2009] [Accepted: 12/01/2009] [Indexed: 12/15/2022]
Abstract
Infliximab (IFX) has tremendously enriched the therapy of inflammatory bowel diseases (IBD) and other immune mediated diseases. Although the efficacy of IFX was undoubtedly proven during the last decade numerous publications have also caused various safety concerns. To summarize the immense information concerning adverse events and safety issues the Austrian Society of Gastroenterology and Hepatology launched this evidence based consensus on the safe use of IFX which covers the following topics: infusion reactions and immunogenicity, skin reactions, opportunistic infections (including tuberculosis), non-opportunistic infections (bacterial and viral), vaccination, neurological complications, hepatotoxicity, congestive heart failure, haematological side effects, intestinal strictures, stenosis and bowel obstruction (SSO), concomitant medication, malignancy and lymphoma, IFX in the elderly and the young, mortality, fertility, pregnancy and breast feeding. To make the vast amount of information practicable for routine application the consensus was finally condensed into a checklist for a safe use of IFX which consists of two parts: issues to be addressed prior to anti-TNF therapy and issues to be addressed during maintenance. Both parts are further divided into obligatory and facultative items.
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Affiliation(s)
- W Miehsler
- Department of Internal Medicine 3, Division of Gastroenterology and Hepatology, Medical University of Vienna, Austria.
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Romberg-Camps M, Kuiper E, Schouten L, Kester A, Hesselink-van de Kruijs M, Limonard C, Bos R, Goedhard J, Hameeteman W, Wolters F, Russel M, Stockbrügger R, Dagnelie P. Mortality in inflammatory bowel disease in the Netherlands 1991-2002: results of a population-based study: the IBD South-Limburg cohort. Inflamm Bowel Dis 2010; 16:1397-410. [PMID: 20027652 DOI: 10.1002/ibd.21189] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The aim was to evaluate overall and disease-specific mortality in a population-based inflammatory bowel disease (IBD) cohort in the Netherlands, as well as risk factors for mortality. METHODS IBD patients diagnosed between 1 January 1991 and 1 January 2003 were included. Standardized mortality ratios (SMRs) were calculated overall and with regard to causes of death, gender, as well as age, phenotype, smoking status at diagnosis, and medication use. RESULTS At the censoring date, 72 out of 1187 patients had died (21 Crohn's disease [CD], 47 ulcerative colitis [UC], and 4 indeterminate colitis [IC] patients). The SMR (95% confidence interval [CI]) was 1.1 (0.7-1.6) for CD, 0.9 (0.7-1.2) for UC and 0.7 (0.2-1.7) for IC. Disease-specific mortality risk was significantly increased for gastrointestinal (GI) causes of death both in CD (SMR 7.5, 95% CI: 2.8-16.4) and UC (SMR 3.4, 95% CI: 1.4-7.0); in CD patients, especially in patients <40 years of age at diagnosis. For UC, an increased SMR was noted in female patients and in patients <19 years and >80 years at diagnosis. In contrast, UC patients had a decreased mortality risk from cancer (SMR 0.5, 95% CI; 0.2-0.9). CONCLUSIONS In this population-based IBD study, mortality in CD, UC, and IC was comparable to the background population. The increased mortality risk for GI causes might reflect complicated disease course, with young and elderly patients at diagnosis needing intensive follow-up. Caution in interpreting the finding on mortality risk from cancer is needed as follow-up was probably to short to observe IBD-related cancers.
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Affiliation(s)
- Mariëlle Romberg-Camps
- Department of Gastroenterology and Hepatology, Maastricht University Medical Center, the Netherlands.
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Dorn SD, Sandler RS. Inflammatory bowel disease is not a risk factor for cardiovascular disease mortality: results from a systematic review and meta-analysis. Am J Gastroenterol 2007; 102:662-7. [PMID: 17156143 DOI: 10.1111/j.1572-0241.2006.01018.x] [Citation(s) in RCA: 84] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES Inflammation in general, and C-reactive protein (CRP) in particular, are closely associated with atherosclerosis. Similarly, the risk of cardiovascular (CV) disease is increased in several systemic inflammatory diseases. The purpose of this study was to examine whether inflammatory bowel disease (IBD) increases CV mortality, an indirect surrogate for CV disease incidence. METHODS A systematic review of studies on CV mortality rates in patients with IBD published between 1965 and 2006 was performed. Studies were included for analysis if they reported data on CV-disease-specific standardized mortality ratios (SMRs) for Crohn's disease (CD) and/or ulcerative colitis (UC). A meta-analysis of SMRs from included studies was performed. RESULTS The review ultimately included 11 studies. Overall there were 4,532 patients with CD and 9,533 patients with UC. SMR point estimates ranged from 0.7 to 1.5 for patients with CD and 0.6-1.1 for patients with UC. There was not a statistically significant increase in CV SMR for either CD or UC in any study. However, two studies demonstrated a statistically significant decrease in CV SMR for UC. Finally, the meta-SMR for CD was 1.0 (95% CI 0.8-1.1) and the meta-SMR for UC was 0.9 (95% CI 0.8-1.0). CONCLUSIONS IBD is not associated with increased CV mortality. Although CV mortality is a suboptimal surrogate for CV disease incidence, this finding provides indirect evidence against an association between IBD and CV disease.
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Affiliation(s)
- Spencer D Dorn
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina 27599-7080, USA
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Jess T, Gamborg M, Munkholm P, Sørensen TIA. Overall and cause-specific mortality in ulcerative colitis: meta-analysis of population-based inception cohort studies. Am J Gastroenterol 2007; 102:609-17. [PMID: 17156150 DOI: 10.1111/j.1572-0241.2006.01000.x] [Citation(s) in RCA: 115] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVES It remains debated whether patients with ulcerative colitis (UC) are at greater risk of dying and whether a possible alteration in mortality can be attributed to specific causes of death. We aimed to clarify this issue by conducting a meta-analysis of population-based inception cohort studies on overall and cause-specific mortality in patients with UC. METHODS The MEDLINE search engine and abstracts from international conferences were searched for relevant literature by use of explicit search criteria. STATA meta-analysis software was used to calculate pooled risk estimates (SMR, standardized mortality ratio, observed/expected deaths) of overall mortality and specific causes of death and to conduct metaregression analyses of the influence of specific variables on SMR. RESULTS Ten papers fulfilled the inclusion criteria, reporting SMRs varying from 0.7 to 1.4. The overall pooled estimate was 1.1 (95% confidence interval [CI] 0.9-1.2, P= 0.42). However, greater risk of dying was observed during the first years of follow-up, in patients with extensive colitis, and in patients from Scandinavia. Metaregression analysis showed an increase in SMR by increasing cohort size. UC-related mortality accounted for 17% of all deaths. Mortality from gastrointestinal diseases, nonalcoholic liver diseases, pulmonary embolisms, and respiratory diseases was increased whereas mortality from pulmonary cancer was reduced. CONCLUSIONS The overall risk of dying in patients with UC did not differ from that of the background population, although subgroups of patients were at greater risk of dying. The cause-of-death distribution seemed to differ from that of the background population.
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Affiliation(s)
- Tine Jess
- Department of Medical Gastroenterology C, Herlev University Hospital, Copenhagen, Denmark
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Kaw LL, Punzalan CK, Crisostomo AC, Bowyer MW, Wherry DC. Surgical pathology of colorectal cancer in Filipinos: implications for clinical practice. J Am Coll Surg 2002; 195:188-95. [PMID: 12168965 DOI: 10.1016/s1072-7515(02)01186-9] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
BACKGROUND A number of studies published in the Philippine literature have demonstrated certain peculiar clinicopathologic characteristics of colorectal cancer among Filipinos. This study presents the latest data and analyzes their implications for clinical practice. STUDY DESIGN The pathology reports of all patients who underwent operation for colorectal cancer at the Philippine General Hospital over a period of 7 years were reviewed. RESULTS One thousand two hundred seventy-seven patients were included. The male to female ratio was almost 1:1. The majority of patients were in the sixth and seventh decades of life, with a mean age of 55.3 years. Patients 40 years of age and younger made up 17% of the total. The site of cancer in order of frequency was rectum (49.8%), left colon (27.9%), and right colon (21.4%). Cancers of the right colon were more common in women, and rectal cancers were more frequent in men. Seventy-six percent of the tumors were well to moderately differentiated adenocarcinomas, and 6.7% were poorly differentiated. Mucinous and signet ring carcinomas were found in 11% and 1% of cases, respectively. Forty-four percent of patients had localized disease at the time of operation, 54% had regional disease, and 2% had disseminated disease. Associated predisposing conditions noted were polyps (4.7%), schistosomiasis (3%), and tuberculosis (1.5%). CONCLUSIONS Colorectal cancer in Filipinos exhibits a number of unique clinicopathologic features, such as a higher proportion of early age of onset tumors, more advanced stage at presentation, an association with chronic granulomatous diseases, and relatively rare occurrence with polyps. This might suggest the possibility of a different pathway for tumor development of colorectal cancer in this population of patients. Also, current screening guidelines advocated for the Western population might not be appropriate for Filipinos.
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Affiliation(s)
- Leoncio L Kaw
- Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
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Joossens S, Reinisch W, Vermeire S, Sendid B, Poulain D, Peeters M, Geboes K, Bossuyt X, Vandewalle P, Oberhuber G, Vogelsang H, Rutgeerts P, Colombel JF. The value of serologic markers in indeterminate colitis: a prospective follow-up study. Gastroenterology 2002; 122:1242-7. [PMID: 11984510 DOI: 10.1053/gast.2002.32980] [Citation(s) in RCA: 191] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND & AIMS In the absence of pathognomonic markers for Crohn's disease (CD) and ulcerative colitis (UC), the diagnosis of inflammatory bowel disease depends on a compendium of clinical, radiographic, endoscopic, and histologic criteria that bears imperfect specificity to the individual disorders. In 10% of cases of colitis, no differentiation can be made between CD and UC; these patients are diagnosed with indeterminate colitis (IC). We evaluated the value of anti-Saccharomyces cerevisiae antibodies (ASCA) and perinuclear antineutrophil cytoplasmic antibodies (pANCA) to increase diagnostic accuracy in categorizing IC. METHODS Since 1996, 97 patients with IC from 3 centers (Leuven, Lille, and Vienna) were enrolled, analyzed for pANCA and ASCA, and followed up prospectively. RESULTS A definitive diagnosis has been reached for 31 of 97 patients (32%). In these patients, ASCA+/pANCA- correlated with CD in 8 of 10 patients, whereas ASCA-/pANCA+ correlated with UC in 7 of 11 patients. The remaining 4 cases became CD, clinically behaving as UC-like CD. Almost half of the patients (47 of 97 [48.5%]) were negative for ASCA and pANCA, and 40 remain diagnosed with IC to date. Only 7 seronegative cases (14.9%) became CD or UC compared with 48% (24 of 50) of seropositive patients (P < 0.001). CONCLUSIONS Results so far show that ASCA+/pANCA- predicts CD in 80% of patients with IC and ASCA-/pANCA+ predicts UC in 63.6%. Interestingly, 48.5% of patients do not show antibodies against ASCA or pANCA. Most of these patients remain diagnosed with IC during their further clinical course, perhaps reflecting a distinct clinicoserological entity.
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Affiliation(s)
- Sofie Joossens
- Gastroenterology Unit, Department of Pathology, U.Z. Gasthuisberg, Leuven, Belgium
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Eaden JA, Abrams KR, Mayberry JF. The risk of colorectal cancer in ulcerative colitis: a meta-analysis. Gut 2001. [PMID: 11247898 DOI: 10.1136/gut484526] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
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.
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Affiliation(s)
- J A Eaden
- Gastrointestinal Research Unit, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK.
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Mandal A, Mayberry J. Magnetic resonance spectroscopy: a new test for differentiating ulcerative colitis from Crohn's disease? Am J Gastroenterol 2001; 96:271-3. [PMID: 11232662 DOI: 10.1111/j.1572-0241.2001.03546.x] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
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Palli D, Trallori G, Bagnoli S, Saieva C, Tarantino O, Ceroti M, d'Albasio G, Pacini F, Amorosi A, Masala G. Hodgkin's disease risk is increased in patients with ulcerative colitis. Gastroenterology 2000; 119:647-53. [PMID: 10982757 DOI: 10.1053/gast.2000.16487] [Citation(s) in RCA: 102] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS All patients diagnosed with ulcerative colitis (UC) or Crohn's disease (CD) residing in Florence, Italy, in 1978-1992 were identified and included in a population-based study of cancer risk evaluation. METHODS A total of 920 patients were followed up (median, 11 years), and 64 newly diagnosed malignancies were identified by linkage to the local cancer registry. Expected cases were calculated on the basis of age- and sex-specific cancer incidence rates to estimate relative risks in comparison with the general population. RESULTS Overall, cancer incidence rates were not increased. A significant excess risk of Hodgkin's disease was observed among patients with UC (standardized incidence ratio, 9.3; 95% confidence interval [CI], 2.5-23.8). Respiratory tract cancers were significantly reduced to one fourth of the expected rate in patients with UC, but tended to be increased among patients with CD, who had a 50% higher risk of cancer at all sites. Only a nonsignificant, modestly increased risk of colorectal cancer was observed. CONCLUSIONS A strongly increased risk of Hodgkin's disease was evident in this first cancer follow-up of a representative series of patients with UC in a Mediterranean country. Two divergent risk patterns of respiratory tract cancers, possibly explained by differences in smoking habits, emerged in the 2 inflammatory bowel diseases.
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Affiliation(s)
- D Palli
- Analytical Epidemiology Branch, Epidemiology Unit, Centro per lo Studio e la Prevenzione Oncologica, Florence, Italy.
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Wandall EP, Damkier P, Møller Pedersen F, Wilson B, Schaffalitzky de Muckadell OB. Survival and incidence of colorectal cancer in patients with ulcerative colitis in Funen county diagnosed between 1973 and 1993. Scand J Gastroenterol 2000; 35:312-7. [PMID: 10766327 DOI: 10.1080/003655200750024209] [Citation(s) in RCA: 19] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND The aim of the study was to determine the death rate and the risk of developing colorectal cancer in patients with ulcerative colitis in Funen County. METHODS The medical records of 801 patients with ulcerative colitis diagnosed in 1973-93 in Funen County were scrutinized with regard to colectomy, survival, and colorectal cancer, and in 1998 a follow-up was carried out. RESULTS The patients were managed at nine different hospitals: one university hospital, one central hospital, and seven smaller hospitals. The mean age at diagnosis was 41 years, and the mean duration of disease was 10.11 years. Sixty-one per cent of the patients were classified as having proctosigmoiditis, 21% as having left-sided colitis, and 18% as having pancolitis. In 127 patients who underwent proctocolectomy during the study period lethal complications occurred in 8 cases: 5 of 110 in Odense University hospital and 3 of 17 in the other hospitals. One hundred and twenty patients in the cohort died during the period of observation, nine of them of colitis-related causes. There was a slightly increased risk of early death in the cohort after 15 years of disease. Six colorectal cancers were found, whereas four were expected, giving a standard incidence ratio of 1.665. The cumulative cancer risk after 20 years' disease duration was 5.3% in the observed group, contrasting with an expected rate of 0.49%, and 10.1% after 25 years. CONCLUSION In this cohort of ulcerative colitis patients the mortality and the risk of developing colorectal cancer were slightly higher than expected compared with the background population.
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Affiliation(s)
- E P Wandall
- Dept. of Medical Gastroenterology S, Odense University Hospital, Denmark
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Williams JG, Cheung WY, Russell IT, Cohen DR, Longo M, Lervy B. Open access follow up for inflammatory bowel disease: pragmatic randomised trial and cost effectiveness study. BMJ (CLINICAL RESEARCH ED.) 2000; 320:544-8. [PMID: 10688560 PMCID: PMC27297 DOI: 10.1136/bmj.320.7234.544] [Citation(s) in RCA: 55] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 02/01/2000] [Indexed: 11/04/2022]
Abstract
OBJECTIVE To evaluate whether follow up of patients with inflammatory bowel disease is better through open access than by routine booked appointments. DESIGN Pragmatic randomised controlled trial. SETTING Two district general hospitals in Swansea and Neath, Wales. PARTICIPANTS 180 adults (78 with Crohn's disease, 77 ulcerative or indeterminate colitis, 25 ulcerative or idiopathic proctitis) recruited from outpatient clinics during October 1995 to November 1996. INTERVENTION Open access follow up according to patient need. MAIN OUTCOME MEASURES Generic (SF-36) and disease specific (UK inflammatory bowel disease questionnaire UKIBDQ) quality of life, number of primary and secondary care contacts, total resource use, and views of patients and general practitioners. RESULTS There were no differences in generic or disease specific quality of life. Open access patients had fewer day visits (0.21 v 0. 42, P<0.05) and fewer outpatient visits ( 4.12 v 4.64, P<0.01), but some patients had difficulty obtaining an urgent appointment. There were no significant differences in specific investigations undertaken, inpatient days, general practitioner surgery or home visits, drugs prescribed, or total patient borne costs. Mean total cost in secondary care was lower for open access patients (P<0.05), but when primary care and patient borne costs were added there were no significant differences in total costs to the NHS or to society. General practitioners and patients preferred open access. CONCLUSIONS Open access follow up delivers the same quality of care as routine outpatient care and is preferred by patients and general practitioners. It uses fewer resources in secondary care but total resource use is similar. Better methods of ensuring urgent access to outpatient clinics are needed.
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Affiliation(s)
- J G Williams
- School of Postgraduate Studies in Medical and Health Care, Morriston Hospital, Swansea SA6 6NL.
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Affiliation(s)
- A Ekbom
- Department of Medical Epidemiology, Karolinska Institutet, Stockholm, Sweden
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Kroser JA, Bachwich DR, Lichtenstein GR. Risk factors for the development of colorectal carcinoma and their modification. Hematol Oncol Clin North Am 1997; 11:547-77. [PMID: 9257146 DOI: 10.1016/s0889-8588(05)70451-2] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
In this article the authors review factors determining risk for the development of colorectal cancer (CC) and their modification. Emphasis is placed on understanding the difference between average risk and high risk individuals. Risk factors including genetics, diet, environment, and coexistent diseases are discussed. The data regarding modification of risk via dietary, pharmaceutical, and prophylactic endoscopic and surgical interventions are reviewed.
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Affiliation(s)
- J A Kroser
- Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia, USA
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Stewénius J, Adnerhill I, Ekelund GR, Florén CH, Fork FT, Janzon L, Lindström C, Ogren M. Risk of relapse in new cases of ulcerative colitis and indeterminate colitis. Dis Colon Rectum 1996; 39:1019-25. [PMID: 8797653 DOI: 10.1007/bf02054693] [Citation(s) in RCA: 38] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
PURPOSE Changes in morbidity pattern of ulcerative colitis have created a need to update understanding of the course of the disease. METHOD A follow-up study was done of relapse rates and progression of inflammation in 571 non-selected patients with ulcerative and indeterminate colitis. RESULTS Relapse rate ten years after diagnosis was 70 percent in definite ulcerative colitis, 22 percent in probable ulcerative colitis, and 77 percent in indeterminate colitis. During the study period, there was no change in the relapse rate. In relapsing proctitis, 52 percent developed more extensive inflammation. Fifty-four percent of patients with only one attack of colitis had persistent signs of inflammatory bowel disease. CONCLUSIONS Shift in morbidity pattern to a greater proportion of patients with proctitis at diagnosis and a shorter time from onset of symptoms to diagnosis had no influence on the relapse rate. Indeterminate colitis has a worse prognosis than definite ulcerative colitis. Considering the documented efficacy of sulfasalazine, the high relapse rate calls for studies of the effectiveness of such treatment in everyday practice.
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Affiliation(s)
- J Stewénius
- Department of Surgery, Malmö University Hospital, Sweden
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