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East JE, Gordon M, Nigam GB, Sinopoulou V, Bateman AC, Din S, Iacucci M, Kabir M, Lamb CA, Wilson A, Al Bakir I, Dhar A, Dolwani S, Faiz O, Hart A, Hayee B, Healey C, Leedham SJ, Novelli MR, Raine T, Rutter MD, Shepherd NA, Subramanian V, Vance M, Wakeman R, White L, Trudgill NJ, Morris AJ. British Society of Gastroenterology guidelines on colorectal surveillance in inflammatory bowel disease. Gut 2025:gutjnl-2025-335023. [PMID: 40306978 DOI: 10.1136/gutjnl-2025-335023] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/05/2025] [Accepted: 03/12/2025] [Indexed: 05/02/2025]
Abstract
Patients with inflammatory bowel disease (IBD) remain at increased risk for colorectal cancer and death from colorectal cancer compared with the general population despite improvements in inflammation control with advanced therapies, colonoscopic surveillance and reductions in environmental risk factors. This guideline update from 2010 for colorectal surveillance of patients over 16 years with colonic inflammatory bowel disease was developed by stakeholders representing UK physicians, endoscopists, surgeons, specialist nurses and patients with GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodological support.An a priori protocol was published describing the approach to three levels of statement: GRADE recommendations, good practice statements or expert opinion statements. A systematic review of 7599 publications, with appraisal and GRADE analysis of trials and network meta-analysis, where appropriate, was performed. Risk thresholding guided GRADE judgements.We made 73 statements for the delivery of an IBD colorectal surveillance service, including outcome standards for service and endoscopist audit, and the importance of shared decision-making with patients.Core areas include: risk of colorectal cancer, IBD-related post-colonoscopy colorectal cancer; service organisation and supporting patient concordance; starting and stopping surveillance, who should or should not receive surveillance; risk stratification, including web-based multivariate risk calculation of surveillance intervals; colonoscopic modalities, bowel preparation, biomarkers and artificial intelligence aided detection; chemoprevention; the role of non-conventional dysplasia, serrated lesions and non-targeted biopsies; management of dysplasia, both endoscopic and surgical, and the structure and role of the multidisciplinary team in IBD dysplasia management; training in IBD colonoscopic surveillance, sustainability (green endoscopy), cost-effectiveness and patient experience. Sixteen research priorities are suggested.
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Affiliation(s)
- James Edward East
- Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
| | - Morris Gordon
- School of Medicine, University of Central Lancashire, Preston, UK
| | - Gaurav Bhaskar Nigam
- Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
| | | | - Adrian C Bateman
- Department of Cellular Pathology, University Hospital Southampton NHS Foundation Trust, Southampton, Southampton, Hampshire, UK
| | - Shahida Din
- The Edinburgh IBD Unit, Western General Hospital, Edinburgh, UK
- Institute of Genetics and Cancer, University of Edinburgh, Edinburgh, UK
| | - Marietta Iacucci
- APC Microbiome Ireland, College of Medicine and Health, University College Cork, Cork, Ireland
| | - Misha Kabir
- Division of Gastrointestinal Services, University College Hospitals NHS Trust, London, UK
| | - Christopher Andrew Lamb
- Translational and Clinical Research Institute, Newcastle University, Newcastle upon Tyne, UK
- Department of Gastroenterology, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - Ana Wilson
- Department of Gastroenterology, St Mark's Hospital and Academic Institute, London, UK
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Ibrahim Al Bakir
- Gastroenterology Department, Chelsea and Westminster Hospital, London, UK
| | - Anjan Dhar
- Department of Gastroenterology, Darlington Memorial Hospital, Darlington, Durham, UK
- Teesside University, Middlesbrough, UK
| | - Sunil Dolwani
- Division of Population Medicine, School of Medicine, Cardiff University, Cardiff, UK
| | - Omar Faiz
- Department of Surgery and Cancer, Imperial College London, London, UK
- Department of Colorectal Surgery, St Mark's Hospital and Academic Institute, London, UK
| | - Ailsa Hart
- Department of Gastroenterology, St Mark's Hospital and Academic Institute, London, UK
- Department of Metabolism, Digestion and Reproduction, Imperial College London, London, UK
| | - Bu'Hussain Hayee
- King's Health Partners Institute for Therapeutic Endoscopy, King's College Hospital NHS Foundation Trust, London, UK
| | - Chris Healey
- Department of Gastroenterology, Airedale NHS Foundation Trust, Keighley, West Yorkshire, UK
| | - Simon John Leedham
- Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
- Stem Cell Biology Lab, Centre for Human Genetics, University of Oxford, Oxford, UK
| | - Marco R Novelli
- Department of Histopathology, University College London, London, UK
| | - Tim Raine
- Department of Gastroenterology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, Cambridgeshire, UK
| | - Matthew D Rutter
- Department of Gastroenterology, University Hospital of North Tees, Stockton-on-Tees, UK
| | - Neil A Shepherd
- Gloucestershire Cellular Pathology Laboratory, Cheltenham General Hospital, Cheltenham, Gloucestershire, UK
| | - Venkataraman Subramanian
- Department of Gastroenterology, St James's University Hospital, Leeds, UK
- Division of Gastroenterology and Surgical Sciences, Leeds Institute of Medical Research, University of Leeds, Leeds, UK
| | - Margaret Vance
- Department of Gastroenterology, St Mark's Hospital and Academic Institute, London, UK
| | | | - Lydia White
- Translational Gastroenterology and Liver Unit, Nuffield Department of Medicine, John Radcliffe Hospital, University of Oxford, Oxford, UK
| | - Nigel J Trudgill
- Department of Gastroenterology, Sandwell and West Birmingham NHS Trust, West Bromwich, UK
- Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
| | - A John Morris
- Department of Gastroenterology, Glasgow Royal Infirmary, Glasgow, UK
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Choi WT, Rabinovitch PS. DNA flow cytometry for detection of genomic instability as a cancer precursor in the gastrointestinal tract. Methods Cell Biol 2024; 186:25-49. [PMID: 38705603 DOI: 10.1016/bs.mcb.2024.02.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 05/07/2024]
Abstract
One of the earliest applications of flow cytometry was the measurement of DNA content in cells. This method is based on the ability to stain DNA in a stoichiometric manner (i.e., the amount of stain is directly proportional to the amount of DNA within the cell). For more than 40years, a number of studies have consistently demonstrated the utility of DNA flow cytometry as a potential diagnostic and/or prognostic tool in patients with most epithelial tumors, including pre-invasive lesions (such as dysplasia) in the gastrointestinal tract. However, its availability as a clinical test has been limited to few medical centers due to the requirement for fresh tissue in earlier studies and perceived technical demands. However, more recent studies have successfully utilized formalin-fixed paraffin-embedded (FFPE) tissue to generate high-quality DNA content histograms, demonstrating the feasibility of this methodology. This review summarizes step-by-step methods on how to perform DNA flow cytometry using FFPE tissue and analyze DNA content histograms based on the published consensus guidelines in order to assist in the diagnosis and/or risk stratification of many different epithelial tumors, with particular emphasis on dysplasia associated with Barrett's esophagus and inflammatory bowel disease.
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Affiliation(s)
- Won-Tak Choi
- Department of Pathology, University of California at San Francisco, San Francisco, CA, United States.
| | - Peter S Rabinovitch
- Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, United States
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Choi WT. Characteristics, Reporting, and Potential Clinical Significance of Nonconventional Dysplasia in Inflammatory Bowel Disease. Surg Pathol Clin 2023; 16:687-702. [PMID: 37863560 DOI: 10.1016/j.path.2023.05.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/22/2023]
Abstract
The term nonconventional dysplasia has been coined to describe several underrecognized morphologic patterns of epithelial dysplasia in inflammatory bowel disease (IBD), but to date, the full recognition of these newly characterized lesions by pathologists is uneven. The identification of nonconventional dysplastic subtypes is becoming increasingly important, as they often present as invisible/flat dysplasia and are more frequently associated with advanced neoplasia than conventional dysplasia on follow-up. This review describes the morphologic, clinicopathologic, and molecular characteristics of seven nonconventional subtypes known to date, as well as their potential significance in the clinical management of IBD patients.
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Affiliation(s)
- Won-Tak Choi
- Department of Pathology, University of California at San Francisco, 505 Parnassus Avenue, M552, Box 0102, San Francisco, CA 94143, USA.
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Khan F, Norton C, Czuber-Dochan W. Knowledge and Attitude of Inflammatory Bowel Disease Patients Toward Colorectal Cancer Risk, Its Management, and the Role of Healthcare Providers: A Cross-Sectional Study in the UK. CROHN'S & COLITIS 360 2023; 5:otad067. [PMID: 37941595 PMCID: PMC10629216 DOI: 10.1093/crocol/otad067] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Indexed: 11/10/2023] Open
Abstract
Background Inflammatory bowel disease (IBD) increases the risk for colorectal cancer (CRC). Limited literature exists on patients' knowledge of CRC risk and management. Attitude toward doctor-recommended management and the role of healthcare providers (HCPs) in CRC risk awareness remain unexplored. This study aimed to fill the gap in knowledge about CRC risk awareness and management in IBD patients in the UK. Methods This cross-sectional internet-based study was conducted in April-July 2019. Adult (>18 years) IBD patients with a confirmed diagnosis for 2 years and adequate command of English language were invited from non-Natinal Health Services sources. A self-designed and piloted questionnaire with open- and closed-ended questions was used. Closed-ended data were analyzed using descriptive statistics and open-ended responses were analyzed using content analysis. Results Ninety-two participants (52.5% Crohn's disease and 67.5% females) responded. Around 88% knew that IBD increased CRC risk. Only 20.7% were aware of colonoscopy as the best screening tool; 88% were unaware of screening initiation time. Almost 90% would agree to a doctor's recommendation of colonoscopy. For dysplasia with 10% risk of CRC, 46.7% would not agree with colectomy. Some 48% reported to have never had a discussion about the risk of CRC in IBD with their HCPs, while 58% were not informed of the role of screening and surveillance in managing CRC risk. Conclusions IBD patients were poorly aware of CRC risk management and had mixed willingness to comply with a doctor's recommendation. HCP's role in cancer knowledge dissemination was suboptimal and patients desired more information.
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Affiliation(s)
- Fiza Khan
- Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King’s College London, London, UK
| | - Christine Norton
- Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King’s College London, London, UK
| | - Wladyslawa Czuber-Dochan
- Florence Nightingale Faculty of Nursing, Midwifery and Palliative Care, King’s College London, London, UK
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Lauricella S, Fabris S, Sylla P. Colorectal cancer risk of flat low-grade dysplasia in inflammatory bowel disease: a systematic review and proportion meta-analysis. Surg Endosc 2023; 37:48-61. [PMID: 35920906 DOI: 10.1007/s00464-022-09462-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/10/2022] [Accepted: 07/09/2022] [Indexed: 01/18/2023]
Abstract
BACKGROUND To date, the optimal management of patients with inflammatory bowel disease (IBD) and flat low-grade dysplasia (fLGD) of the colon or rectum remains controversial. METHODS A systematic review was reported in accordance with PRISMA 2020 (Preferred Reporting Items for Systematic Reviews and Meta-Analyses). Patients diagnosed with fLGD on surveillance endoscopy were pooled from studies published between 2000 and 2020. Advanced neoplasia was defined by the presence of HGD, CRC or small bowel adenocarcinoma detected on subsequent surveillance endoscopy or from examination of resection specimens. We estimated the pooled annual incidence rate of colorectal cancer (CRC) and advanced neoplasia, and the risk factors associated with neoplastic progression. RESULTS We identified 24 articles and 738 IBD patients were diagnosed with fLGD on endoscopy. Two hundred thirty-six patients (32%) underwent immediate surgery with surgical specimens demonstrating CRC in 8 patients (pooled prevalence, 8.66%; 95% CI 3.58-19.46) and HGD (high grade dysplasia) in 11 patients (pooled prevalence, 13.97%; 95% CI 5.65-30.65). Five hundred-two patients (68%) underwent endoscopic surveillance with 63 patients with fLGD progressing to advanced neoplasia during endoscopic surveillance (38 HGD, 24 CRC and one patient developing small bowel adenocarcinoma). The mean duration of follow-up after fLGD diagnosis was 71 months (10.9-212). The pooled incidence of CRC and advanced neoplasia was 0.5 (95% CI 0.23-0.77) and 1.71 per 100 patient-year (95% CI 0.88-2.54) respectively. The use of corticosteroids and location of fLGD in the distal colon were significantly associated with neoplastic progression. CONCLUSIONS This study provides a summary incidence rate of CRC and advanced neoplasia in patients with IBD and fLGD to inform surgeons' and endoscopists' decision-making thus reducing potential ineffective treatments.
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Affiliation(s)
- Sara Lauricella
- Division of Colon and Rectal Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA. .,Department of Colon and Rectal Surgery, Icahn School of Medicine at Mount Sinai Hospital, 5 E 98th St 14th Fl, Ste D, New York, NY, 10029, USA.
| | - Silvia Fabris
- Unit of Medical Statistic and Epidemiology, Department of Medicine, Campus Bio-Medico of Rome University, Rome, Italy
| | - Patricia Sylla
- Division of Colon and Rectal Surgery, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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Chazouilleres O, Beuers U, Bergquist A, Karlsen TH, Levy C, Samyn M, Schramm C, Trauner M. EASL Clinical Practice Guidelines on sclerosing cholangitis. J Hepatol 2022; 77:761-806. [PMID: 35738507 DOI: 10.1016/j.jhep.2022.05.011] [Citation(s) in RCA: 162] [Impact Index Per Article: 54.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2022] [Accepted: 05/16/2022] [Indexed: 02/07/2023]
Abstract
Management of primary or secondary sclerosing cholangitis is challenging. These Clinical Practice Guidelines have been developed to provide practical guidance on debated topics including diagnostic methods, prognostic assessment, early detection of complications, optimal care pathways and therapeutic (pharmacological, endoscopic or surgical) options both in adults and children.
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Choi WT, Kővári BP, Lauwers GY. The Significance of Flat/Invisible Dysplasia and Nonconventional Dysplastic Subtypes in Inflammatory Bowel Disease: A Review of Their Morphologic, Clinicopathologic, and Molecular Characteristics. Adv Anat Pathol 2022; 29:15-24. [PMID: 34469911 DOI: 10.1097/pap.0000000000000316] [Citation(s) in RCA: 15] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/26/2022]
Abstract
Patients with inflammatory bowel disease are at significantly increased risk of dysplasia and colorectal cancer (CRC). The early detection, histologic grading, and removal of dysplasia plays a critical role in preventing the development of CRC. With advances in endoscopic visualization and resection techniques, colectomy is no longer recommended to manage dysplasia, unless surveillance colonoscopy detects flat/invisible dysplasia (either high-grade dysplasia or multifocal low-grade dysplasia) or an endoscopically unresectable lesion. Although there are numerous review articles and book chapters on the morphologic criteria of conventional (intestinal type) dysplasia, the most well-recognized form of dysplasia, at least 7 distinct nonconventional morphologic patterns of epithelial dysplasia have been recently described in inflammatory bowel disease. Most practicing pathologists are not familiar with these nonconventional subtypes and thus, may even overlook some of these dysplastic lesions as benign or reactive. However, the recognition of these subtypes is important, as some of them appear to have a high risk of developing advanced neoplasia (high-grade dysplasia or CRC) and often show molecular alterations characteristic of advanced neoplasia. This review briefly describes the morphologic criteria of conventional dysplasia but predominantly focuses on all 7 nonconventional subtypes as well as our understanding of their clinicopathologic and molecular features that can assist in their risk stratification.
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Affiliation(s)
- Won-Tak Choi
- Department of Pathology, University of California at San Francisco, San Francisco, CA
| | - Bence P Kővári
- Department of Pathology, H. Lee Moffitt Cancer Center, Tampa, FL
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Parian AM, Limketkai BN, Chowdhury R, Brewer GG, Salem G, Falloon K, Selaru F, Melia J, Lazarev MG. Serrated Epithelial Change Is Associated With High Rates of Neoplasia in Ulcerative Colitis Patients: A Case-controlled Study and Systematic Review With Meta-analysis. Inflamm Bowel Dis 2021; 27:1475-1481. [PMID: 33295614 DOI: 10.1093/ibd/izaa312] [Citation(s) in RCA: 17] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2020] [Indexed: 12/23/2022]
Abstract
BACKGROUND Patients with long-standing ulcerative colitis (UC) are at an increased risk of colorectal cancer. Risk stratification is important to identify patients who require more frequent endoscopic surveillance. Serrated epithelial change (SEC) found in patients with long-standing colitis may be associated with neoplasia and serve as a marker to stratify patients at higher risk of colorectal cancer (CRC). METHODS A case-control study was performed to compare the rates of neoplasia between UC patients with SEC and UC patients without SEC who were matched for age, disease duration, and disease extent. Paired tests, conditional logistic regression, and Kaplan-Meier analyses were used to compare groups. A systematic review with meta-analysis was performed, combining our local data with previously published data. RESULTS This study included 196 UC patients without prior neoplasia, 98 with SEC and 98 without SEC. Ulcerative colitis patients with SEC had a significantly higher rate of synchronous or metachronous neoplasia than UC patients without SEC (26.5% vs 3.1%; P < 0.001). Synchronous or metachronous high-grade dysplasia and CRC were found more frequently in UC patients with SEC than UC patients without SEC (11.2% vs 2.0%; P = 0.02). A meta-analysis was consistent with these findings, showing a higher rate of neoplasia in patients with SEC compared with those without SEC (16.4% vs 3.9%; P < 0.001). CONCLUSION Serrated epithelial change is associated with a significantly increased risk of synchronous and metachronous neoplasia including high-grade dysplasia and CRC in patients with UC. Histopathological findings of SEC should warrant closer endoscopic surveillance for CRC.
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Affiliation(s)
- Alyssa M Parian
- Department of Gastroenterology & Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Berkeley N Limketkai
- Department of Gastroenterology & Hepatology, Johns Hopkins University, Baltimore, MD, USA.,Vatche & Tamar Manoukian Division of Digestive Diseases, UCLA School of Medicine, Los Angeles, CA, USA
| | - Reezwana Chowdhury
- Department of Gastroenterology & Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Gala Godoy Brewer
- Department of Gastroenterology & Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - George Salem
- Department of Gastroenterology & Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Katie Falloon
- Department of Gastroenterology, Cleveland Clinic, Cleveland, OH, USA
| | - Florin Selaru
- Department of Gastroenterology & Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Joanna Melia
- Department of Gastroenterology & Hepatology, Johns Hopkins University, Baltimore, MD, USA
| | - Mark G Lazarev
- Department of Gastroenterology & Hepatology, Johns Hopkins University, Baltimore, MD, USA
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Tanaka S, Saitoh Y, Matsuda T, Igarashi M, Matsumoto T, Iwao Y, Suzuki Y, Nozaki R, Sugai T, Oka S, Itabashi M, Sugihara KI, Tsuruta O, Hirata I, Nishida H, Miwa H, Enomoto N, Shimosegawa T, Koike K. Evidence-based clinical practice guidelines for management of colorectal polyps. J Gastroenterol 2021; 56:323-335. [PMID: 33710392 PMCID: PMC8005396 DOI: 10.1007/s00535-021-01776-1] [Citation(s) in RCA: 62] [Impact Index Per Article: 15.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 02/27/2021] [Indexed: 02/04/2023]
Abstract
BACKGROUND The Japanese Society of Gastroenterology (JSGE) published ''Daicho Polyp Shinryo Guideline 2014'' in Japanese and a part of this guideline was published in English as "Evidence-based clinical practice guidelines for management of colorectal polyps" in the Journal of Gastroenterology in 2015. A revised version of the Japanese-language guideline was published in 2020, and here we introduce a part of the contents of revised version. METHODS The guideline committee discussed and drew up a series of clinical questions (CQs). Recommendation statements for the CQs were limited to items with multiple therapeutic options. Items with established conclusions that had 100% agreement with previous guidelines (background questions) and items with no (or old) evidence that are topics for future research (future research questions: FRQs) were given descriptions only. To address the CQs and FRQs, PubMed, ICHUSHI, and other sources were searched for relevant articles published in English from 1983 to October 2018 and articles published in Japanese from 1983 to November 2018. The Japan Medical Library Association was also commissioned to search for relevant materials. Manual searches were performed for questions with insufficient online references. RESULTS The professional committee created 18 CQs and statements concerning the current concept and diagnosis/treatment of various colorectal polyps, including their epidemiology, screening, pathophysiology, definition and classification, diagnosis, management, practical treatment, complications, and surveillance after treatment, and other colorectal lesions (submucosal tumors, nonneoplastic polyps, polyposis, hereditary tumors, ulcerative colitis-associated tumors/carcinomas). CONCLUSIONS After evaluation by the moderators, evidence-based clinical practice guidelines for management of colorectal polyps were proposed for 2020. This report addresses the therapeutic related CQs introduced when formulating these guidelines.
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Affiliation(s)
- Shinji Tanaka
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan.
- Department of Endoscopy, Hiroshima University Hospital, 1-2-3 Minami-ku, KasumiHiroshima, 734-8551, Japan.
| | - Yusuke Saitoh
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Takahisa Matsuda
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Masahiro Igarashi
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Takayuki Matsumoto
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yasushi Iwao
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Yasumoto Suzuki
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Ryoichi Nozaki
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tamotsu Sugai
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Shiro Oka
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Michio Itabashi
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Ken-Ichi Sugihara
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Osamu Tsuruta
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Ichiro Hirata
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hiroshi Nishida
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Hiroto Miwa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Nobuyuki Enomoto
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Tooru Shimosegawa
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
| | - Kazuhiko Koike
- Guidelines Committee for Creating and Evaluating the "Evidence-Based Clinical Practice Guidelines for Management of Colorectal Polyps", the Japanese Society of Gastroenterology (JSGE), 6F Shimbashi i-MARK Bldg., 2-6-2 Shimbashi, Minato-ku, Tokyo, 105-0004, Japan
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Choi WT. Non-conventional dysplastic subtypes in inflammatory bowel disease: a review of their diagnostic characteristics and potential clinical implications. J Pathol Transl Med 2021; 55:83-93. [PMID: 33677953 PMCID: PMC7987516 DOI: 10.4132/jptm.2021.02.17] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/15/2021] [Accepted: 02/17/2021] [Indexed: 12/26/2022] Open
Abstract
The early detection and grading of dysplasia is the current standard of care to minimize mortality from colorectal cancer (CRC) in patients with inflammatory bowel disease. With the development of advanced endoscopic resection techniques, colectomy is now reserved for patients with invisible/flat dysplasia (either high-grade [HGD] or multifocal low-grade dysplasia) or endoscopically unresectable lesions. Although most pathologists are familiar with the morphologic criteria of conventional (intestinal type) dysplasia, the most well-recognized form of dysplasia, an increasing number of diagnostic material has led to the recognition of several different morphologic patterns of epithelial dysplasia. The term “non-conventional” dysplasia has been coined to describe these changes, but to date, the recognition and full appreciation of these novel forms of dysplasia by practicing pathologists is uneven. The recognition of these non-conventional subtypes is becoming increasingly important, as some of them appear to have a higher risk of developing HGD or CRC than conventional dysplasia or sporadic adenomas. This review describes the morphologic characteristics of all seven non-conventional subtypes that have been reported to date as well as our current understanding of their clinicopathologic and molecular features that distinguish them from conventional dysplasia or sporadic adenomas.
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Affiliation(s)
- Won-Tak Choi
- Department of Pathology, University of California at San Francisco, San Francisco, CA, USA
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11
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Lightner AL, Vogler S, McMichael J, Jia X, Regueiro M, Qazi T, Steele SR. Dysplastic Progression to Adenocarcinoma is Equivalent in Ulcerative Colitis and Crohn's Disease. J Crohns Colitis 2021; 15:24-34. [PMID: 32592468 DOI: 10.1093/ecco-jcc/jjaa133] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
BACKGROUND We sought to determine the rate of progression from dysplasia to adenocarcinoma in ulcerative colitis [UC] vs Crohn's diseases [CD] and describe the risk factors unique to each. METHODS All adult patients [≥18 years] with a known diagnosis of either UC or CD who underwent a surveillance colonoscopy between January 1, 2010 and January 1, 2020 were included. RESULTS A total of 23 751 surveillance colonoscopies were performed among 12 289 patients between January 1, 2010 and January 1, 2020; 6909 [56.2%] had a diagnosis of CD and 5380 [43.8%] had a diagnosis of UC. There were a total of 668 patients [5.4%] with low-grade dysplasia [LGD], 76 patients [0.62%] with high-grade dysplasia [HGD], and 68 patients [0.55%] with adenocarcinoma in the series; the majority of the dysplastic events were located in the right colon. Significantly more UC patients had a dysplastic event, but the rate of LGD and HGD dysplasia progression to adenocarcinoma was not significantly different in CD or UC [p = 0.682 and p = 1.0, respectively]. There was no significant difference in the rate of progression from LGD/HGD to adenocarcinoma based on random biopsies vs targeted biopsies of visible lesions [p = 0.37]. However, the rate of progression from LGD vs HGD to adenocarcinoma was significantly greater for HGD [p < 0.001]. CONCLUSION While more UC patients were found to have neoplasia on colonoscopy, the rate of progression from LGD and HGD to adenocarcinoma was equivalent in UC and CD, suggesting that endoscopic surveillance strategies can remain consistent for all IBD patients.
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Affiliation(s)
- Amy L Lightner
- Department of Colorectal Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Sarah Vogler
- Department of Colorectal Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, Cleveland, OH, USA
| | - John McMichael
- General Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Xue Jia
- General Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Miguel Regueiro
- Department of Gastroenterology, Digestive Disease Surgical Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Taha Qazi
- Department of Gastroenterology, Digestive Disease Surgical Institute, Cleveland Clinic, Cleveland, OH, USA
| | - Scott R Steele
- Department of Colorectal Surgery, Digestive Disease Surgical Institute, Cleveland Clinic, Cleveland, OH, USA
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12
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Kabir M, Fofaria R, Arebi N, Bassett P, Tozer PJ, Hart AL, Thomas-Gibson S, Humphries A, Suzuki N, Saunders B, Warusavitarne J, Faiz O, Wilson A. Systematic review with meta-analysis: IBD-associated colonic dysplasia prognosis in the videoendoscopic era (1990 to present). Aliment Pharmacol Ther 2020; 52:5-19. [PMID: 32432797 DOI: 10.1111/apt.15778] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2020] [Revised: 02/02/2020] [Accepted: 04/17/2020] [Indexed: 12/14/2022]
Abstract
INTRODUCTION The prognosis of dysplasia in patients with IBD is largely determined from observational studies from the pre-videoendoscopic era (pre-1990s) that does not reflect recent advances in endoscopic imaging and resection. AIMS To better understand the risk of synchronous colorectal cancer and metachronous advanced neoplasia (ie high-grade dysplasia or cancer) associated with dysplasia diagnosed in the videoendoscopic era, and to stratify risk according to a lesion's morphology, endoscopic resection status or whether it was incidentally detected on biopsy of macroscopically normal colonic mucosa (ie invisible). METHODS A systematic search of original articles published between 1990 and February 2020 was performed. Eligible studies reported on incidence of advanced neoplasia at follow-up colectomy or colonoscopy for IBD-dysplasia patients. Quantitative and qualitative analyses were performed. RESULTS Thirty-three studies were eligible for qualitative analysis (five for the meta-analysis). Pooled estimated proportions of incidental synchronous cancers found at colectomy performed for a pre-operative diagnosis of visible high-grade dysplasia, invisible high-grade dysplasia, visible low-grade dysplasia and invisible low-grade dysplasia were 13.7% (95% CI 0.0-54.1), 11.4% (95% CI 4.6-20.3), 2.7% (95% CI 0.0-7.1) and 2.4% (95% CI 0.0-8.5) respectively. The lowest incidences of metachronous advanced neoplasia, for dysplasia not managed with immediate colectomy but followed up with surveillance, tended to be reported by the studies where high definition imaging and/or chromoendoscopy was used and endoscopic resection of visible dysplasia was histologically confirmed. CONCLUSIONS The prognosis of IBD-dysplasia diagnosed in the videoendoscopic era appears to have been improved but the quality of evidence remains low. Larger, prospective studies are needed to guide management. PROSPERO registration no: CRD42019105736.
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Affiliation(s)
- Misha Kabir
- St Mark's Hospital, Harrow, UK.,Imperial College London, London, UK
| | | | - Naila Arebi
- St Mark's Hospital, Harrow, UK.,Imperial College London, London, UK
| | | | - Phil J Tozer
- St Mark's Hospital, Harrow, UK.,Imperial College London, London, UK
| | - Ailsa L Hart
- St Mark's Hospital, Harrow, UK.,Imperial College London, London, UK
| | | | - Adam Humphries
- St Mark's Hospital, Harrow, UK.,Imperial College London, London, UK
| | - Noriko Suzuki
- St Mark's Hospital, Harrow, UK.,Imperial College London, London, UK
| | - Brian Saunders
- St Mark's Hospital, Harrow, UK.,Imperial College London, London, UK
| | | | - Omar Faiz
- St Mark's Hospital, Harrow, UK.,Imperial College London, London, UK
| | - Ana Wilson
- St Mark's Hospital, Harrow, UK.,Imperial College London, London, UK
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13
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The impact of gut microbiota manipulation with antibiotics on colon tumorigenesis in a murine model. PLoS One 2019; 14:e0226907. [PMID: 31860645 PMCID: PMC6924659 DOI: 10.1371/journal.pone.0226907] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/27/2019] [Accepted: 12/07/2019] [Indexed: 12/30/2022] Open
Abstract
It has been suggested that manipulation of gut microbiota using antibiotics can inhibit colitis-associated colorectal cancer (CAC) in a mouse model. We investigated whether timing of gut microbial manipulation using antibiotics affects colon tumorigenesis in the azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced CAC model. CAC was induced in C57BL/6 mice by injection of 12.5 mg/kg AOM followed by three rounds of 1.7% DSS exposure. There were six groups based on timing of antibiotic administration. Colonic inflammation, proliferation, and tumorigenesis were evaluated after animal sacrifice. High-throughput sequencing of the mice feces was performed to characterize changes in gut microbiota. Full-time antibiotic treatment significantly decreased the number and size of tumors, histological scores, and expression of pro-inflammatory cytokines compared to the AOM/DSS group without antibiotic treatment. The early and late antibiotic groups, antibiotic administration from the first and second rounds of DSS to the end of the study, showed significantly lower histological scores and tumor burden. In contrast, the pretreatment antibiotic group, antibiotic administration from 3 weeks prior to AOM to the first round of DSS, did not exhibit decreased tumorigenesis. Principal coordinate analysis showed similar gut microbial community structures among the full-time, early, and late antibiotic groups, whereas other groups showed distinct gut microbial profiles. There was a positive correlation between number of tumors and number of operational taxonomic units. Colonic tumorigenesis was attenuated by antibiotic administration, except for that only prior to DSS administration, suggesting that gut microbial changes should be maintained throughout the entire period of inflammation to suppress tumorigenesis.
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14
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Löwenberg M, Van Der Vlugt M. Risk of Progression of Low-Grade Dysplasia to Advanced Neoplasia in Inflammatory Bowel Disease. J Crohns Colitis 2019; 13:1483-1484. [PMID: 31314882 DOI: 10.1093/ecco-jcc/jjz118] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Mark Löwenberg
- Amsterdam UMC, University of Amsterdam, Department of Gastroenterology and Hepatology, Meibergdreef, Amsterdam, The Netherlands
| | - Manon Van Der Vlugt
- Amsterdam UMC, University of Amsterdam, Department of Gastroenterology and Hepatology, Meibergdreef, Amsterdam, The Netherlands
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15
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Shah SC, Itzkowitz SH. Management of Inflammatory Bowel Disease-Associated Dysplasia in the Modern Era. Gastrointest Endosc Clin N Am 2019; 29:531-548. [PMID: 31078251 PMCID: PMC7354094 DOI: 10.1016/j.giec.2019.02.008] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
This article begins with a brief overview of risk factors for colorectal neoplasia in inflammatory bowel disease to concretize the approach to risk stratification. It then provides an up-to-date review of diagnosis and management of dysplasia in inflammatory bowel disease, which integrates new and emerging data in the field. This is particularly relevant in an era of increased attention to cost- and resource-containment from the health systems vantage point, coupled with a heightened prioritization of patient quality of life and shared decision-making. Also provided is a brief discussion of the status of newer therapeutic techniques, such as endoscopic submucosal dissection.
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Affiliation(s)
- Shailja C. Shah
- Division of Gastroenterology, Hepatology and Nutrition, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA
| | - Steven H. Itzkowitz
- Division of Gastroenterology, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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16
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Kotsafti A, D'Incà R, Scarpa M, Fassan M, Angriman I, Mescoli C, Bortoli N, Brun P, Bardini R, Rugge M, Savarino E, Zingone F, Castoro C, Castagliuolo I, Scarpa M. Weak Cytotoxic T Cells Activation Predicts Low-Grade Dysplasia Persistence in Ulcerative Colitis. Clin Transl Gastroenterol 2019; 10:e00061. [PMID: 31343468 PMCID: PMC6708661 DOI: 10.14309/ctg.0000000000000061] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/11/2019] [Accepted: 05/16/2019] [Indexed: 12/12/2022] Open
Abstract
INTRODUCTION In patients with ulcerative colitis (UC), dysplasia develops in 10%-20% of cases. The persistence of low-grade dysplasia (LGD) in UC in 2 consecutive observations is still an indication for restorative proctocolectomy. Our hypothesis is that in the case of weak cytotoxic activation, dysplasia persists. We aimed to identify possible immunological markers of LGD presence and persistence. METHODS We prospectively enrolled 112 UC patients who underwent screening colonoscopy (T0) who had biopsies taken from their sigmoid colon. Ninety of them had at least a second colonoscopy (T1) with biopsies taken in the sigmoid colon and 8 patients had dysplasia in both examinations suggesting a persistence of LGD in their colon. Immunohistochemistry and real time polymerase chain reaction for CD4, CD69, CD107, and CD8β messenger RNA (mRNA) expression and flow cytometry for epithelial cells expressing CD80 or HLA avidin-biotin complex were performed. Non-parametric statistics, receiver operating characteristic curves analysis, and logistic multiple regression analysis were used. RESULTS Thirteen patients had LGD diagnosed at T0. The mucosal mRNA expression of CD4, CD69, and CD8β was significantly lower than in patients without dysplasia (P = 0.033, P = 0.046 and P = 0.007, respectively). A second colonoscopy was performed in 90 patients after a median follow-up of 17 (12-25) months and 14 of the patients were diagnosed with LGD. In these patients, CD8β mRNA expression at T0 was significantly lower in patients without dysplasia (P = 0.004). A multivariate survival analysis in a model including CD8β mRNA levels and age >50 demonstrated that both items were independent predictors of dysplasia at follow-up (hazard ratio [HR] = 0.47 [95% confidence interval [CI]: 0.26-0.86], P = 0.014, and HR = 13.32 [95% CI: 1.72-102.92], P = 0.013). DISCUSSION These data suggest a low cytotoxic T cell activation in the colonic mucosa of UC patients who do not manage to clear dysplasia. Thus, low level of CD8β mRNA expression in non-dysplastic colonic mucosa might be considered in future studies about the decision making of management of LGD in UC.
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MESH Headings
- Adult
- Antigens, CD/metabolism
- Antigens, Differentiation, T-Lymphocyte/metabolism
- B7-1 Antigen/metabolism
- Biopsy
- CD4 Antigens/metabolism
- CD8 Antigens/metabolism
- Colitis, Ulcerative/diagnostic imaging
- Colitis, Ulcerative/pathology
- Colon, Sigmoid/pathology
- Colonoscopy/methods
- Female
- Humans
- Hyperplasia/classification
- Hyperplasia/pathology
- Immunohistochemistry/instrumentation
- Intestinal Mucosa/metabolism
- Intestinal Mucosa/pathology
- Lectins, C-Type/metabolism
- Lysosomal-Associated Membrane Protein 1/metabolism
- Lysosomal-Associated Membrane Protein 2/metabolism
- Male
- Middle Aged
- Proctocolectomy, Restorative/standards
- Prospective Studies
- RNA, Messenger/metabolism
- Survival Analysis
- T-Lymphocytes, Cytotoxic/metabolism
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Affiliation(s)
- Andromachi Kotsafti
- Laboratory of Advanced Translational Research, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy
| | - Renata D'Incà
- Gastroenterology Unit, Azienda Ospedaliera di Padova, Padova, Italy
| | - Melania Scarpa
- Laboratory of Advanced Translational Research, Veneto Institute of Oncology IOV - IRCCS, Padova, Italy
| | - Matteo Fassan
- Department of Medicine, University of Padova, Padova, Italy
| | - Imerio Angriman
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | | | - Nicolò Bortoli
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Paola Brun
- Department of Molecular Medicine, University of Padova, Padova, Italy
| | - Romeo Bardini
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Massimo Rugge
- Department of Medicine, University of Padova, Padova, Italy
| | - Edoardo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Fabiana Zingone
- Department of Surgery, Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Carlo Castoro
- Upper GI Surgery Unit, Istituto Humanitas, Rozzano, Italy
| | | | - Marco Scarpa
- General Surgery Unit, Azienda Ospedaliera di Padova, Padova, Italy
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17
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Mark-Christensen A, Laurberg S, Haboubi N. Dysplasia in Inflammatory Bowel Disease: Historical Review, Critical Histopathological Analysis, and Clinical Implications. Inflamm Bowel Dis 2018; 24:1895-1903. [PMID: 29668897 DOI: 10.1093/ibd/izy075] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/08/2017] [Indexed: 12/16/2022]
Affiliation(s)
- Anders Mark-Christensen
- Department of Surgery, Section of Coloproctology, Aarhus University Hospital, Aarhus C, Denmark
| | - Søren Laurberg
- Department of Surgery, Section of Coloproctology, Aarhus University Hospital, Aarhus C, Denmark
| | - Najib Haboubi
- Department of Pathology, Spire Hospital Manchester, Manchester, England
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18
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Mahid S, Minor K, Brangers B, Cobbs G, Galandiuk S. SMAD2 and the Relationship of Colorectal Cancer to Inflammatory Bowel Disease. Int J Biol Markers 2018. [DOI: 10.1177/172460080802300306] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023]
Abstract
Inflammatory bowel diseases (IBDs) affecting the colon [Crohn's disease (CD) and ulcerative colitis (UC)] are associated with an increased risk of colorectal cancer (CRC). Our previous work using oligonucleotide array data indicated that SMAD2 was significantly underexpressed in UC dysplastic tissue compared to benign UC. The aim of this current study was to determine whether single nucleotide polymorphisms (SNPs) within the SMAD2 gene are associated with IBD dysplasia/cancer. We performed an SNP haplotype-based case-control association study. Leukocyte DNA was obtained from 489 unrelated Caucasians (158 UC, 175 CD, 71 CRC, 85 controls). Eleven SNPs were genotyped. All 11 SNPs were in Hardy-Weinberg equilibrium in the control population. Strong linkage disequilibrium was observed among nearly all SMAD2 SNPs. There were no significant associations between SMAD2 allele or haplotype frequencies. Power calculations indicated good power for single-marker analysis (>0.8) and reasonably good power against effects of 0.1–0.15 for haplotype analysis. SMAD2 SNPs were not associated with the development of IBD dysplasia/cancer. This incongruity between our previous microarray data and the findings from this genotype study may be attributed to mechanisms such as alternative splicing of pre-mRNA SMAD2 and/or cross talk with other cellular pathways.
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Affiliation(s)
- S.S. Mahid
- Price Institute of Surgical Research and the Section of Colorectal Surgery, Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky
| | - K.S. Minor
- Price Institute of Surgical Research and the Section of Colorectal Surgery, Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky
| | - B.C. Brangers
- Price Institute of Surgical Research and the Section of Colorectal Surgery, Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky
| | - G.A. Cobbs
- Department of Biology, University of Louisville, Kentucky - USA
| | - S. Galandiuk
- Price Institute of Surgical Research and the Section of Colorectal Surgery, Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky
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19
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Flores BM, O'Connor A, Moss AC. Impact of mucosal inflammation on risk of colorectal neoplasia in patients with ulcerative colitis: a systematic review and meta-analysis. Gastrointest Endosc 2017; 86:1006-1011.e8. [PMID: 28750838 DOI: 10.1016/j.gie.2017.07.028] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Accepted: 07/14/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Long-standing ulcerative colitis is an established risk factor for colorectal neoplasia. A number of observational studies have suggested that evidence of mucosal inflammation (endoscopic or histologic) is associated with a greater risk for colorectal neoplasia than is mucosal healing. Our goal was to systematically analyze the risk of colorectal neoplasia in patients with ulcerative colitis who have ongoing mucosal inflammation to better inform surveillance strategies. METHODS We performed a systematic review and meta-analysis of the effect of endoscopic and/or histologic inflammation on the risk of colorectal neoplasia in cohort and case-control studies. Sensitivity analyses for study setting and case definition were performed. RESULTS Six studies met the inclusion criteria, incorporating outcomes in 1443 patients. No study used a single validated measure for mucosal inflammation. The pooled odds ratio for colorectal neoplasia was 3.5 (95% confidence interval [CI], 2.6-4.8; P < .001) in those with any mucosal inflammation and 2.6 (95% CI, 1.5-4.5; P = .01) in those with histologic inflammation, when compared with those with mucosal healing. The overall quality of the studies was good. CONCLUSION The presence of objective evidence of mucosal inflammation during follow-up in patients with ulcerative colitis is associated with a greater risk of subsequent colorectal neoplasia than in those with mucosal healing. This risk factor should be considered in guidelines on surveillance intervals for these patients.
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Affiliation(s)
- Brisas M Flores
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Anthony O'Connor
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom
| | - Alan C Moss
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
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20
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Aabakken L, Karlsen TH, Albert J, Arvanitakis M, Chazouilleres O, Dumonceau JM, Färkkilä M, Fickert P, Hirschfield GM, Laghi A, Marzioni M, Fernandez M, Pereira SP, Pohl J, Poley JW, Ponsioen CY, Schramm C, Swahn F, Tringali A, Hassan C. Role of endoscopy in primary sclerosing cholangitis: European Society of Gastrointestinal Endoscopy (ESGE) and European Association for the Study of the Liver (EASL) Clinical Guideline. J Hepatol 2017; 66:1265-1281. [PMID: 28427764 DOI: 10.1016/j.jhep.2017.02.013] [Citation(s) in RCA: 67] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Accepted: 02/14/2017] [Indexed: 02/06/2023]
Abstract
This guideline is an official statement of the European Society of Gastrointestinal Endoscopy (ESGE) and of the European Association for the Study of the Liver (EASL) on the role of endoscopy in primary sclerosing cholangitis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system was adopted to define the strength of recommendations and the quality of evidence. Main recommendations.
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Tontini GE, Rath T, Pastorelli L, Vecchi M, Neumann H. Surveillance strategies for colitis-associated cancer: state of the art and future perspectives. Expert Rev Gastroenterol Hepatol 2017; 11:427-437. [PMID: 28276810 DOI: 10.1080/17474124.2017.1297705] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Colitis-associated cancer (CAC) represents a concrete risk of morbidity and mortality in patients with long lasting inflammatory bowel diseases. Surveillance colonoscopy is a rapidly evolving research field with profound changes from the traditional approach based on scheduled controls and random biopsy protocols. Areas covered: A literature search was performed using PubMed/Embase to review the latest evidence supporting the need for surveillance colonoscopy. By focusing on the most promising recent advances in this field, we provide a state-of-the-art overview of the current gold standards for the diagnosis and management of colitis-associated dysplasia. Expert commentary: Evidence-based and emerging data have questioned the efficacy and effectiveness of both standard surveillance colonoscopy and random biopsy protocols. The latest guidelines endorse early initiation of surveillance programs, risk-profiling assessment of colonoscopy intervals and standardized use of advanced imaging modalities to detect early dysplasia. Current trends clearly reveal increased attention to direct visualization and endoscopic management of visible dysplastic lesions, even in patients with longstanding colitis. Emerging technological advances in gastrointestinal endoscopy are expected to change the endoscopic surveillance protocols in the near future.
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Affiliation(s)
- Gian Eugenio Tontini
- a Gastroenterology and Digestive Endoscopy Unit , IRCCS Policlinico San Donato , San Donato Milanese , Italy
| | - Timo Rath
- b Department of Medicine I , University of Erlangen-Nuremberg , Erlangen , Germany
| | - Luca Pastorelli
- a Gastroenterology and Digestive Endoscopy Unit , IRCCS Policlinico San Donato , San Donato Milanese , Italy
- c Department of Biomedical Sciences for Health , University of Milan , Milano , Italy
| | - Maurizio Vecchi
- a Gastroenterology and Digestive Endoscopy Unit , IRCCS Policlinico San Donato , San Donato Milanese , Italy
- c Department of Biomedical Sciences for Health , University of Milan , Milano , Italy
| | - Helmut Neumann
- b Department of Medicine I , University of Erlangen-Nuremberg , Erlangen , Germany
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23
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The miR-200 family is increased in dysplastic lesions in ulcerative colitis patients. PLoS One 2017; 12:e0173664. [PMID: 28288169 PMCID: PMC5348010 DOI: 10.1371/journal.pone.0173664] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2017] [Accepted: 02/26/2017] [Indexed: 12/15/2022] Open
Abstract
Background Colorectal cancer (CRC) is a life-threatening complication of ulcerative colitis (UC), and patients are routinely screened for the development of precancerous lesions (dysplasia). However, rates of CRC development in patients with confirmed low-grade dysplasia vary widely between studies, suggesting a large degree of heterogeneity between these lesions that is not detectable macroscopically. A better understanding of the underlying molecular changes that occur in dysplasia will help to identify lesions at higher risk of malignancy. MicroRNAs (miRNAs) post-transcriptionally regulate protein expression and cell-signalling networks. Aberrant miRNA expression is a feature of sporadic CRC but much less is known about the changes that occur in dysplasia and in UC. Methods Comprehensive microRNA profiling was performed on RNA extracted from UC dysplastic lesions (n = 7) and UC controls (n = 10). The expression of miRNAs in UC post inflammatory polyps (n = 7) was also assessed. Candidate miRNAs were further validated by qPCR, and miRNA in situ hybridization. Serum levels of miRNAs were also assessed with a view to identification of non-invasive biomarkers of dysplasia. Results UC dysplasia was associated with a shift in miRNA expression profiles that was not seen in inflammatory polyps. In particular, levels of miR-200b-3p were increased in dysplasia, and this miRNA was localised to epithelial cells in dysplastic lesions and in UC cancers. No changes in miRNA levels were detected in the serum. Conclusion UC-Dysplasia is linked to altered miRNA expression in the mucosa and elevated miR-200b-3p levels.
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Parian A, Koh J, Limketkai BN, Eluri S, Rubin DT, Brant SR, Ha CY, Bayless TM, Giardiello F, Hart J, Montgomery E, Lazarev MG. Association between serrated epithelial changes and colorectal dysplasia in inflammatory bowel disease. Gastrointest Endosc 2016; 84:87-95.e1. [PMID: 26709112 PMCID: PMC5555397 DOI: 10.1016/j.gie.2015.12.010] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2015] [Accepted: 12/06/2015] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Serrated epithelial change (SEC) is a histologic finding in longstanding colitis that may be associated with dysplasia. Our primary aim was to determine the incidence of dysplasia and colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients with SEC. Secondary aims were to determine the rate of location concordance between SEC and dysplasia/CRC and to identify other risk factors associated with dysplasia in IBD patients with SEC. METHODS A retrospective, descriptive, observational study was performed by searching the Pathology Data System at a single tertiary referral center for a histologic finding of "serrated epithelial change." The patient's first pathology specimen with SEC was designated the index SEC. All subsequent pathology reports were evaluated for the occurrence and location of dysplasia or CRC. Univariable and multivariable logistic regression were performed to identify predictors of dysplasia. RESULTS There were 187 patients with confirmed IBD and 1 or more histologic findings of SEC without prior dysplasia. Mean IBD duration was 16 years, and median follow-up time was 28 months. The rate of high-grade dysplasia or CRC was 17 per 1000 patient-years. Thirty-nine of 187 patients (21%) had synchronous or metachronous dysplasia or CRC. Location concordance was 68%. Multivariable analysis found SEC on follow-up examinations, older age at IBD diagnosis, male gender, and a first-degree relative with CRC were associated with dysplasia in IBD patients with SEC. CONCLUSIONS This uncontrolled study describes a high frequency of dysplasia in patients with a histologic finding of SEC. SEC seen on successive endoscopic examinations further increased the risk of dysplasia. Further controlled studies are needed to determine if SEC is a precancerous lesion in IBD patients and if SEC can be endoscopically identified.
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Affiliation(s)
- Alyssa Parian
- Division of Gastroenterology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Joyce Koh
- Division of Gastroenterology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Berkeley N. Limketkai
- Division of Gastroenterology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA,Division of Gastroenterology & Hepatology, Stanford University School of Medicine, Stanford, California, USA
| | - Swathi Eluri
- Department of Medicine, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - David T. Rubin
- Department of Medicine, University of Chicago, Chicago, Illinois, USA
| | - Steven R. Brant
- Division of Gastroenterology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Christina Y. Ha
- Division of Gastroenterology, University of California Los Angeles, Los Angeles, California, USA
| | - Theodore M. Bayless
- Division of Gastroenterology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Francis Giardiello
- Division of Gastroenterology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - John Hart
- Department of Pathology, University of Chicago, Chicago, Illinois, USA
| | - Elizabeth Montgomery
- Department of Pathology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
| | - Mark G. Lazarev
- Division of Gastroenterology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
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25
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Deepak P, Hanson GJ, Fletcher JG, Tremaine WJ, Pardi DS, Kisiel JB, Schroeder KW, Wong Kee Song LM, Harmsen WS, Loftus EV, Bruining DH. Incremental diagnostic yield of chromoendoscopy and outcomes in inflammatory bowel disease patients with a history of colorectal dysplasia on white-light endoscopy. Gastrointest Endosc 2016; 83:1005-12. [PMID: 26408903 DOI: 10.1016/j.gie.2015.09.021] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/13/2015] [Accepted: 09/17/2015] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Chromoendoscopy (CE) identifies dysplastic lesions with a higher sensitivity than white-light endoscopy (WLE). The role of CE in the management of dysplasia on surveillance WLE in inflammatory bowel disease (IBD) remains unclear. METHODS A retrospective cohort of IBD patients with colorectal dysplasia on WLE who subsequently underwent CE between January 1, 2006 and August 31, 2013 was identified. Endoscopic and histologic findings were compared among the index WLE, first CE, and subsequent CE. Outcomes assessed included endoscopic lesion removal, surgery or repeat CE, and diagnosis of colorectal cancer. RESULTS Ninety-five index cases were identified. The median duration of IBD was 18 years (interquartile range 9.3-29.8); 78 patients had ulcerative colitis. Dysplasia was identified in 55 patients during the index WLE with targeted biopsies of 72 lesions. The first CE visualized dysplastic lesions in 50 patients, including 34 new lesions (not visualized on the index examination). Endoscopic resection was performed successfully of 43 lesions, most in the cecum/ascending colon (n = 20) with sessile morphology (n = 33). After the first CE, 14 patients underwent surgery that revealed 2 cases of colorectal cancer and 3 cases of high-grade dysplasia. Multiple CEs were performed in 44 patients. Of these, 20 patients had 34 visualized lesions, 26 of which were new findings. CONCLUSION Initial and subsequent CE performed in IBD patients with a history of colorectal dysplasia on WLE frequently identified new lesions, most of which were amenable to endoscopic treatment. These data support the use of serial CEs in this high-risk population.
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Affiliation(s)
- Parakkal Deepak
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | | | - Joel G Fletcher
- Division of Abdominal Imaging, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - William J Tremaine
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Darrell S Pardi
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - John B Kisiel
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Kenneth W Schroeder
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Louis M Wong Kee Song
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - William S Harmsen
- Division of Biomedical Statistics and Informatics, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Edward V Loftus
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - David H Bruining
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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26
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Rossi RE, Conte D, Massironi S. Primary sclerosing cholangitis associated with inflammatory bowel disease: an update. Eur J Gastroenterol Hepatol 2016; 28:123-131. [PMID: 26636407 DOI: 10.1097/meg.0000000000000532] [Citation(s) in RCA: 46] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic progressive disease, usually associated with underlying inflammatory bowel diseases (IBDs), with a prevalence of 60-80% in western countries. Herein, we review the current knowledge about the association between PSC and IBD in terms of clinical approach and long-term patient management. A PubMed search was conducted for English-language publications from 2000 through 2015 using the following keywords: primary sclerosing cholangitis, inflammatory bowel disease, ulcerative colitis, Crohn's disease, diagnosis, therapy, follow-up, and epidemiology. In terms of diagnosis, liver function tests and histology are currently used. The medical treatment options for PSC associated with IBD do not differ from the cases of PSC alone, and include ursodeoxycholic acid and immunosuppressive agents. These treatments do not seem to improve survival, even if ursodeoxycholic acid given at low doses may be chemopreventive against colorectal cancer (CRC). Liver transplantation is the only potential curative therapy for PSC with reported survival rates of 85 and 70% at 5 and 10 years after transplant; however, there is a risk for PSC recurrence, worsening of IBD activity, and de-novo IBD occurrence after liver transplantation. PSC-IBD represents an important public health concern, especially in view of the increased risk for malignancy, including CRC. Long-life annual surveillance colonoscopy is usually recommended, although the exact timescale is still unclear. Further studies are required both to clarify whether annual colonoscopy is cost-effective, especially in younger patients, and to identify potential pharmaceutical agents and genetic targets that may retard disease progression and protect against CRC.
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Affiliation(s)
- Roberta E Rossi
- aGastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda - Ospedale Maggiore Policlinico bDepartment of Pathophysiology and Organ Transplantation, Università degli Studi di Milano, Milan, Italy
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27
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Ooi CJ, Makharia GK, Hilmi I, Gibson PR, Fock KM, Ahuja V, Ling KL, Lim WC, Thia KT, Wei SC, Leung WK, Koh PK, Gearry RB, Goh KL, Ouyang Q, Sollano J, Manatsathit S, de Silva HJ, Rerknimitr R, Pisespongsa P, Abu Hassan MR, Sung J, Hibi T, Boey CCM, Moran N, Leong RWL. Asia-Pacific consensus statements on Crohn's disease. Part 2: Management. J Gastroenterol Hepatol 2016; 31:56-68. [PMID: 25819311 DOI: 10.1111/jgh.12958] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 03/11/2015] [Indexed: 02/05/2023]
Abstract
The Asia Pacific Working Group on Inflammatory Bowel Disease was established in Cebu, Philippines, at the Asia Pacific Digestive Week conference in 2006 under the auspices of the Asian Pacific Association of Gastroenterology (APAGE) with the goal of developing best management practices, coordinating research and raising awareness of IBD in the region. The consensus group previously published recommendations for the diagnosis and management of ulcerative colitis (UC) with specific relevance to the Asia-Pacific region. The present consensus statements were developed following a similar process to address the epidemiology, diagnosis and management of Crohn's disease (CD). The goals of these statements are to pool the pertinent literature specifically highlighting relevant data and conditions in the Asia-Pacific region relating to the economy, health systems, background infectious diseases, differential diagnoses and treatment availability. It does not intend to be all-comprehensive and future revisions are likely to be required in this ever-changing field.
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Affiliation(s)
- Choon Jin Ooi
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Govind K Makharia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Ida Hilmi
- Division of Gastroenterology and Hepatology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Peter R Gibson
- Monash University Department of Medicine, Box Hill Hospital, Melbourne, Victoria, Australia
| | - Kwong Ming Fock
- Department of Gastroenterology, Changi General Hospital, Singapore
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Khoon Lin Ling
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Wee Chian Lim
- Department of Gastroenterology, Tan Tock Seng Hospital, Singapore
| | - Kelvin T Thia
- Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore
| | - Shu-chen Wei
- Department of Internal Medicine, National Taiwan University, Taipei, Taiwan
| | | | - Poh Koon Koh
- Department of Colorectal Surgery, Singapore General Hospital, Singapore
| | - Richard B Gearry
- Department of Medicine, University of Otago, Christchurch, New Zealand
| | - Khean Lee Goh
- Division of Gastroenterology and Hepatology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia
| | - Qin Ouyang
- Division of Gastroenterology, Department of Internal Medicine, West China Hospital, Sichuan University, Chengdu, China
| | - Jose Sollano
- Department of Medicine, University of Santo Tomas, Manila, Philippines
| | - Sathaporn Manatsathit
- Department of Medicine, Division of Gastroenterology, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - H Janaka de Silva
- Department of Medicine, Faculty of Medicine, University of Kelaniya, Colombo, Sri Lanka
| | - Rungsun Rerknimitr
- Division of Gastroenterology, Department of Medicine, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
| | - Pises Pisespongsa
- Division of Gastroenterology, Department of Internal Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand
| | | | - Joseph Sung
- Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong
| | | | | | - Neil Moran
- Gastroenterology and Liver Services, Concord Hospital, Sydney, New South Wales, Australia
| | - Rupert W L Leong
- Gastroenterology and Liver Services, Concord Hospital, Sydney, New South Wales, Australia
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28
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Yang DH. [Recent Advances in Understanding Colorectal Cancer and Dysplasia Related to Ulcerative Colitis]. THE KOREAN JOURNAL OF GASTROENTEROLOGY 2015; 66:312-9. [PMID: 26691188 DOI: 10.4166/kjg.2015.66.6.312] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Ulcerative colitis is an idiopathic chronic inflammatory bowel disease and its incidence in Korea has rapidly increased over the past two decades. Since ulcerative colitis is associated with increased risk for colorectal cancer, annual or biannual colonoscopy with four quadrant random biopsies at every 10 cm segments has been recommended for surveillance of colitic cancer in patients with long standing left-sided or extensive colitis. Recent epidemiologic data and meta-analysis suggest that the increment of colorectal cancer risk in ulcerative colitis was not larger than that of previous studies. Moreover, in addition to the extent and duration of colitis, other risk factors such as family history of colorectal cancer, primary sclerosing cholangitis, stricture, pseudopolyps, and histologic severity of inflammation have been recognized. As a result, updated guidelines provide surveillance strategies adjusted to the individual patient's risk for colitic cancer. Regarding surveillance method, target biopsy under panchromoendoscopy is preferentially recommended rather than random biopsy.
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Affiliation(s)
- Dong-Hoon Yang
- Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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29
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Low-grade dysplasia in ulcerative colitis: risk factors for developing high-grade dysplasia or colorectal cancer. Am J Gastroenterol 2015; 110:1461-71; quiz 1472. [PMID: 26416190 PMCID: PMC4697133 DOI: 10.1038/ajg.2015.248] [Citation(s) in RCA: 99] [Impact Index Per Article: 9.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/03/2015] [Accepted: 07/07/2015] [Indexed: 12/11/2022]
Abstract
OBJECTIVES The aim of this study was to identify risk factors associated with development of high-grade dysplasia (HGD) or colorectal cancer (CRC) in ulcerative colitis (UC) patients diagnosed with low-grade dysplasia (LGD). METHODS Patients with histologically confirmed extensive UC, who were diagnosed with LGD between 1993 and 2012 at St Mark's Hospital, were identified and followed up to 1 July 2013. Demographic, endoscopic, and histological data were collected and correlated with the development of HGD or CRC. RESULTS A total of 172 patients were followed for a median of 48 months from the date of initial LGD diagnosis (interquartile range (IQR), 15-87 months). Overall, 33 patients developed HGD or CRC (19.1% of study population; 20 CRCs) during study period. Multivariate Cox proportional hazard analysis revealed that macroscopically non-polypoid (hazard ratio (HR), 8.6; 95% confidence interval (CI), 3.0-24.8; P<0.001) or invisible (HR, 4.1; 95% CI, 1.3-13.4; P=0.02) dysplasia, dysplastic lesions ≥1 cm in size (HR, 3.8; 95% CI, 1.5-13.4; P=0.01), and a previous history of "indefinite for dysplasia" (HR, 2.8; 95% CI, 1.2-6.5; P=0.01) were significant contributory factors for HGD or CRC development. Multifocal dysplasia (HR, 3.9; 95% CI, 1.9-7.8; P<0.001), metachronous dysplasia (HR, 3.5; 95% CI, 1.6-7.5; P=0.001), or a colonic stricture (HR, 7.4; 95% CI, 2.5-22.1; P<0.001) showed only univariate correlation to development of HGD or CRC. CONCLUSIONS Lesions that are non-polypoid or endoscopically invisible, large (≥1 cm), or preceded by indefinite dysplasia are independent risk factors for developing HGD or CRC in UC patients diagnosed with LGD.
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30
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Horvath B, Liu G, Wu X, Lai KK, Shen B, Liu X. Overexpression of p53 predicts colorectal neoplasia risk in patients with inflammatory bowel disease and mucosa changes indefinite for dysplasia. Gastroenterol Rep (Oxf) 2015; 3:344-9. [PMID: 26063242 PMCID: PMC4650973 DOI: 10.1093/gastro/gov022] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/06/2015] [Accepted: 05/11/2015] [Indexed: 12/24/2022] Open
Abstract
Background and aims: We previously demonstrated a significant colorectal neoplasia risk in inflammatory bowel disease (IBD) patients with mucosal changes indefinite for dysplasia (IND) and the potential diagnostic utility of p53 and cytokeratin 7 immunohistochemistry in IBD-associated neoplasia. The primary aim of this exploratory study was to determine the predictive value of the two markers for neoplasia risk in the IBD-IND population. Methods: We identified 44 eligible cases with IBD and IND in colon biopsy from our pathology database. We semi-quantified the expression of p53 and cytokeratin 7 in the colon biopsies by immunohistochemistry and correlated their expression, demographic information, and clinical features with colorectal neoplasia outcome. Results: The mean age of the cohort was 46.6 ± 15.1 years, with 25 (56.8%) being male. The median follow-up was 101 months (range: 6–247) after IND diagnosis. Among these 44 patients, 11 (25%) progressed to neoplasia (low-grade dysplasia = 6; high-grade dysplasia = 2; cancer 3) at a median follow-up of 66 months (range: 19–145). Univariate analysis demonstrated that age and p53 overexpression were associated with progression to neoplasia. Conclusions: Twenty-five percent of patients with IBD and IND developed colorectal dysplasia or cancer. Overexpression of p53 and age are associated with neoplastic progression.
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Affiliation(s)
- Bela Horvath
- Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA
| | - Ganglei Liu
- Department of Geriatric Surgery, the Second Xiangya Hospital of Central South University, Changsha, China, Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH, USA
| | - Xianrui Wu
- Department of Colorectal Surgery, the Sixth Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Keith K Lai
- Department of Pathology, University of Arkansas for Medical Sciences, Little Rock, AR, USA and
| | - Bo Shen
- Department of Gastroenterology/Hepatology, Cleveland Clinic, Cleveland, OH, USA
| | - Xiuli Liu
- Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH, USA,
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31
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SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastrointest Endosc 2015; 81:489-501.e26. [PMID: 25708752 DOI: 10.1016/j.gie.2014.12.009] [Citation(s) in RCA: 269] [Impact Index Per Article: 26.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Accepted: 12/09/2014] [Indexed: 02/08/2023]
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32
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Laine L, Kaltenbach T, Barkun A, McQuaid KR, Subramanian V, Soetikno R, Farraye FA, Feagan B, Ioannidis J, Kiesslich R, Krier M, Matsumoto T, McCabe RP, Mönkemüller K, Odze R, Picco M, Rubin DT, Rubin M, Rubio CA, Rutter MD, Sanchez-Yague A, Sanduleanu S, Shergill A, Ullman T, Velayos F, Yakich D, Yang YX. SCENIC international consensus statement on surveillance and management of dysplasia in inflammatory bowel disease. Gastroenterology 2015; 148:639-651.e28. [PMID: 25702852 DOI: 10.1053/j.gastro.2015.01.031] [Citation(s) in RCA: 388] [Impact Index Per Article: 38.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/09/2014] [Accepted: 12/09/2014] [Indexed: 02/08/2023]
Affiliation(s)
- Loren Laine
- Section of Digestive Diseases, Yale School of Medicine, New Haven, Connecticut; Veterans Affairs Connecticut Healthcare System, West Haven, Connecticut
| | - Tonya Kaltenbach
- Veterans Affairs Palo Alto Healthcare System and Stanford University School of Medicine (affiliate), Palo Alto, California
| | - Alan Barkun
- Division of Gastroenterology, McGill University, Montreal, Quebec, Canada
| | - Kenneth R McQuaid
- University of California at San Francisco, Veterans Affairs Medical Center, San Francisco, California
| | | | - Roy Soetikno
- Veterans Affairs Palo Alto Healthcare System and Stanford University School of Medicine (affiliate), Palo Alto, California
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Øresland T, Bemelman WA, Sampietro GM, Spinelli A, Windsor A, Ferrante M, Marteau P, Zmora O, Kotze PG, Espin-Basany E, Tiret E, Sica G, Panis Y, Faerden AE, Biancone L, Angriman I, Serclova Z, de Buck van Overstraeten A, Gionchetti P, Stassen L, Warusavitarne J, Adamina M, Dignass A, Eliakim R, Magro F, D'Hoore A. European evidence based consensus on surgery for ulcerative colitis. J Crohns Colitis 2015; 9:4-25. [PMID: 25304060 DOI: 10.1016/j.crohns.2014.08.012] [Citation(s) in RCA: 243] [Impact Index Per Article: 24.3] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
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34
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van Assche G, Dignass A, Bokemeyer B, Danese S, Gionchetti P, Moser G, Beaugerie L, Gomollón F, Häuser W, Herrlinger K, Oldenburg B, Panes J, Portela F, Rogler G, Stein J, Tilg H, Travis S, Lindsay JO. [Second European evidence-based consensus on the diagnosis and management of ulcerative colitis Part 3: Special situations (Spanish version)]. REVISTA DE GASTROENTEROLOGIA DE MEXICO 2015; 80:74-106. [PMID: 25769216 DOI: 10.1016/j.rgmx.2014.10.008] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/16/2014] [Accepted: 10/23/2014] [Indexed: 12/12/2022]
Affiliation(s)
- G van Assche
- En nombre de la ECCO; G.V.A. y A.D. actúan como coordinadores del consenso y han contribuido igualmente para este trabajo.
| | - A Dignass
- G.V.A. y A.D. actúan como coordinadores del consenso y han contribuido igualmente para este trabajo.
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35
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Friis-Ottessen M, Burum-Auensen E, Schjølberg AR, Ekstrøm PO, Andersen SN, Clausen OP, De Angelis PM. TP53/p53 alterations and Aurora A expression in progressor and non-progressor colectomies from patients with longstanding ulcerative colitis. Int J Mol Med 2014; 35:24-30. [PMID: 25333414 PMCID: PMC4249752 DOI: 10.3892/ijmm.2014.1974] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/25/2014] [Accepted: 09/16/2014] [Indexed: 12/12/2022] Open
Abstract
Aneuploidy is a common feature in the colonic mucosa of patients suffering from the inflammatory bowel disease ulcerative colitis (UC) and often precedes the development of dysplasia and cancer. Aneuploidy is assumed to be caused by missegregation of chromosomes during mitosis, often due to a faulty spindle assembly checkpoint. p53 is a tumour suppressor protein known to regulate the spindle assembly checkpoint and is frequently mutated in aneuploid cells. Aurora A is a presumed oncoprotein, also involved in regulation of the spindle assembly checkpoint. In the present study, we examined the mutational frequency of TP53 and the protein levels of p53 in a set of 20 progressor and 10 non-progressor colectomies from patients suffering from longstanding UC. In addition, we re-examined previously published immunohistochemical data on Aurora A expression using the same material. Levels of Aurora A were re-examined with regard to DNA ploidy status and dysplasia within the progressors, as well as in relation to p53 accumulation and TP53 mutational status. We detected p53 accumulation only within the progressor colectomies, where it could be followed back 14 years prior to the colectomies, in pre-colectomy biopsies. TP53 mutations were detected in both progressors and non-progressors. Expression levels of Aurora A were similar in the progressors and non-progressors. Within the group of progressors however, low levels of Aurora A were associated with areas of DNA aneuploidy, as well as with increasing degrees of dysplasia. Our results indicate that alterations in p53 may be an early biomarker of a progressor colon, and that p53 is accumulated early in UC-related carcinogenesis. Furthermore, a decreased Aurora A expression is associated with the development of DNA aneuploidy, as well as with dysplasia in UC progressors.
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Affiliation(s)
- Mariann Friis-Ottessen
- Division of Diagnostics and Intervention, Department of Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
| | | | | | - Per Olaf Ekstrøm
- Division of Surgery and Cancer Medicine, Institute for Cancer Research, The Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - Solveig N Andersen
- Department of Pathology, Akershus University Hospital, Division of Medicine and Laboratory Sciences, University of Oslo, Oslo, Norway
| | | | - Paula M De Angelis
- Division of Diagnostics and Intervention, Department of Pathology, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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Tsaitas C, Semertzidou A, Sinakos E. Update on inflammatory bowel disease in patients with primary sclerosing cholangitis. World J Hepatol 2014; 6:178-187. [PMID: 24799986 PMCID: PMC4009473 DOI: 10.4254/wjh.v6.i4.178] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2013] [Revised: 03/05/2014] [Accepted: 03/13/2014] [Indexed: 02/06/2023] Open
Abstract
Patients with primary sclerosing cholangitis (PSC) complicated by inflammatory bowel disease (IBD) represent a distinct subset of patients with unique characteristics, which have serious clinical implications. The aim of this literature review was to shed light to the obscure clinical and molecular aspects of the two diseases combined utilizing current data available and putting issues of diagnosis and treatment into perspective. The prevalence of IBD, mainly ulcerative colitis in PSC patients is estimated to be 21%-80%, dependent on screening programs and nationality. PSC-associated colitis is likely to be extensive, characterized by rectal sparing, backwash ileitis, and generally mild symptoms. It is also more likely to progress to colorectal malignancy, making it imperative for clinicians to maintain a high level of suspicion when tackling PSC patients. There is no optimal surveillance strategy but current guidelines advocate that colonoscopy is necessary at the time of PSC diagnosis with annual endoscopic follow-up. Random biopsies have been criticized and a shift towards targeted biopsies using chromoendoscopy, laser endomicroscopy and narrow-band imaging has been noted. Techniques directed towards genetic mutations instead of histological abnormalities hold promise for easier, more accurate diagnosis of dysplastic lesions. Chemopreventive measures against colorectal cancer have been sought in these patients. Ursodeoxycholic acid seemed promising at first but subsequent studies yielded conflicting results showing anticarcinogenic effects in low doses (8-15 mg/kg per day) and carcinogenic properties in high doses (15-30 mg/kg per day).
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Affiliation(s)
- Christos Tsaitas
- Christos Tsaitas, Anysia Semertzidou, Emmanouil Sinakos, 4 Internal Medicine Unit, University Hospital of Thessaloniki, Thessaloniki 54642, Greece
| | - Anysia Semertzidou
- Christos Tsaitas, Anysia Semertzidou, Emmanouil Sinakos, 4 Internal Medicine Unit, University Hospital of Thessaloniki, Thessaloniki 54642, Greece
| | - Emmanouil Sinakos
- Christos Tsaitas, Anysia Semertzidou, Emmanouil Sinakos, 4 Internal Medicine Unit, University Hospital of Thessaloniki, Thessaloniki 54642, Greece
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Tontini GE, Vecchi M, Neurath MF, Neumann H. Review article: newer optical and digital chromoendoscopy techniques vs. dye-based chromoendoscopy for diagnosis and surveillance in inflammatory bowel disease. Aliment Pharmacol Ther 2013; 38:1198-208. [PMID: 24117471 DOI: 10.1111/apt.12508] [Citation(s) in RCA: 34] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2013] [Revised: 07/16/2013] [Accepted: 09/05/2013] [Indexed: 12/11/2022]
Abstract
BACKGROUND Recent innovations in gastrointestinal endoscopy have changed our traditional approach to diagnosis and therapy in patients with inflammatory bowel diseases (IBD). While traditionally used dye-based chromoendoscopy (DBC) techniques suffer from several limitations that reduce their utility in daily routine practice, newer 'dye-less' chromoendoscopy (DLC) techniques offer a great potential to overcome most of these limitations. AIM To review available optical and digital chromoendoscopy techniques, by critically discussing their potential for diagnostic and surveillance colonoscopy in patients with IBD. METHODS A literature search on the use of dye-less and dye-based chromoendoscopy in IBD patients was performed. RESULTS In long-standing IBD, DBC improves detection of dysplasia (diagnostic odds ratio = 17.5, 95% CI = 1.2-247.1) as well as prediction of inflammatory disease activity and extent of disease compared with standard video-colonoscopy. Narrow band imaging (NBI) shows no improvement in dysplasia detection rates compared with white-light endoscopy and DBC (P = 0.6). Moreover, NBI results in a suboptimal differentiation of dysplastic from nondysplastic lesions. No data regarding digital DLC techniques (i.e. FICE, i-scan) for dysplasia detection in IBD are yet available. Both NBI and i-scan are superior to white-light endoscopy in assessing the activity and extent of colorectal IBD. CONCLUSIONS Although the potential benefits of newer optical and digital dye-less chromoendoscopy techniques over traditionally used DBC are substantial, only DBC can currently be recommended to improve dysplasia detection in long-standing IBD. In contrast, DLC has the potential to quantify disease activity and mucosal healing in IBD.
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Affiliation(s)
- G E Tontini
- Department of Medicine I, University of Erlangen-Nuremberg, Erlangen, Germany; Gastroenterology and Digestive Endoscopy Unit, IRCCS Policlinico San Donato, San Donato Milanese, Italy
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Eaton JE, Smyrk TC, Imam M, Pardi DS, Loftus EV, Owens VL, Talwalkar JA. The fate of indefinite and low-grade dysplasia in ulcerative colitis and primary sclerosing cholangitis colitis before and after liver transplantation. Aliment Pharmacol Ther 2013; 38:977-87. [PMID: 24033551 DOI: 10.1111/apt.12469] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/26/2013] [Revised: 05/08/2013] [Accepted: 08/12/2013] [Indexed: 12/15/2022]
Abstract
BACKGROUND Patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at an increased risk of colorectal neoplasia, but it is unknown if liver transplantation (LT) alters neoplasia progression. AIM To examine the natural history of indefinite dysplasia (IND) and low-grade dysplasia (LGD) that develop in patients with PSC-UC with and without LT. METHODS We performed a retrospective review of patients with PSC and UC evaluated at our institution between 1993 and 2011 who were diagnosed with IND or LGD before or after LT for PSC. The primary end point was neoplasia progression or persistent LGD. RESULTS Ninety-six patients (non-LT n = 63, LT n = 33) were examined. For the IND group, multifocal lesions were significantly associated with time to neoplasia progression [hazard ratio (HR), 3.5; 95% confidence interval (CI), 1.3-9.7], while 5-aminosalicylate (5-ASA) use was protective (HR, 0.2; 95% CI, 0.1-0.6). For patients with LGD, multifocal lesions were significantly associated with the primary end point (HR, 7.1; 95% CI, 1.7-28.3), while LT was protective (HR, 0.3; 95% CI, 0.1-0.9). CONCLUSIONS In PSC-UC patients with IND, 5-ASA use was associated with a decreased the risk of neoplasia progression, regardless of transplant status. In contrast, multifocal IND and LGD were associated with neoplasia progression or persistent LGD. Patients who developed LGD following LT for PSC were less likely to have progressive neoplasia or persistent LGD, compared with those who had not been transplanted.
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Affiliation(s)
- J E Eaton
- Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA
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Chaparro M, Trapero-Marugán M, Guijarro M, López C, Moreno-Otero R, Gisbert JP. Dysplasia and colorectal cancer in a patient with ulcerative colitis and primary sclerosing cholangitis: a case report and a short review of the literature. J Crohns Colitis 2013; 7:e61-5. [PMID: 22552273 DOI: 10.1016/j.crohns.2012.04.005] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/05/2011] [Revised: 04/01/2012] [Accepted: 04/03/2012] [Indexed: 02/07/2023]
Abstract
Primary sclerosing cholangitis is a chronic progressive disorder which involves the medium size and large ducts in the intrahepatic and extrahepatic biliary tree. The great majority of cases have underlying inflammatory bowel disease, mainly ulcerative colitis. A higher risk of colorectal cancer has been described among ulcerative colitis patients with primary sclerosing cholangitis. Here we report a case of a primary sclerosing cholangitis in a young male with a newly diagnosed ulcerative colitis presenting with colonic dysplasia. Surveillance for colorectal cancer should be strongly recommended in this group of patients.
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Affiliation(s)
- María Chaparro
- Department of Gastroenterology, Hospital Universitario de La Princesa, Instituto de Investigación Sanitaria Princesa and Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Madrid, Spain.
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Mescoli C, Albertoni L, D'incá R, Rugge M. Dysplasia in inflammatory bowel diseases. Dig Liver Dis 2013; 45:186-94. [PMID: 22974564 DOI: 10.1016/j.dld.2012.07.013] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/24/2012] [Revised: 07/06/2012] [Accepted: 07/18/2012] [Indexed: 12/11/2022]
Abstract
In both Crohn's disease and ulcerative colitis, the secondary prevention of colorectal cancer basically relies on the histological detection of dysplasia. In inflammatory bowel diseases, dysplasia identifies the subgroup of patients eligible for stricter surveillance (or prophylactic colectomy). In clinical practice, a number of issues may influence the benefits of clinico-pathological surveillance for inflammatory bowel disease patients with dysplasia, including: sampling errors, inconsistent biopsy assessments, patients' compliance with follow-up requirements, and how heath care is organized. Even in such a multifaceted context, it has been demonstrated that dysplasia surveillance is effective in reducing colorectal cancer-related mortality and morbidity. This paper focuses on current issues concerning the histological assessment of inflammatory bowel disease-associated dysplastic lesions.
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Affiliation(s)
- Claudia Mescoli
- Department of Medicine (DIMED), Surgical Pathology & Cytopathology Unit, University of Padova, Italy
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Van Assche G, Dignass A, Bokemeyer B, Danese S, Gionchetti P, Moser G, Beaugerie L, Gomollón F, Häuser W, Herrlinger K, Oldenburg B, Panes J, Portela F, Rogler G, Stein J, Tilg H, Travis S, Lindsay JO. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 3: special situations. J Crohns Colitis 2013; 7:1-33. [PMID: 23040453 DOI: 10.1016/j.crohns.2012.09.005] [Citation(s) in RCA: 334] [Impact Index Per Article: 27.8] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/30/2012] [Accepted: 09/03/2012] [Indexed: 02/07/2023]
Affiliation(s)
- Gert Van Assche
- Division of Gastroenterology, Department of Medicine, Mt. Sinai Hospital and University Health Network,University of Toronto and University of Leuven, 600 University Avenue, Toronto, ON, Canada M5G 1X5.
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Dyson JK, Rutter MD. Colorectal cancer in inflammatory bowel disease: What is the real magnitude of the risk? World J Gastroenterol 2012; 18:3839-48. [PMID: 22876036 PMCID: PMC3413056 DOI: 10.3748/wjg.v18.i29.3839] [Citation(s) in RCA: 160] [Impact Index Per Article: 12.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/06/2012] [Revised: 05/22/2012] [Accepted: 05/26/2012] [Indexed: 02/06/2023] Open
Abstract
The association between inflammatory bowel disease (IBD) and colorectal cancer (CRC) has been recognised since 1925 and still accounts for 10%-15% of deaths in IBD. IBD-associated CRC (IBD-CRC) affects patients at a younger age than sporadic CRC. The prognosis for sporadic CRC and IBD-CRC is similar, with a 5-year survival of approximately 50%. Identifying at risk patients and implementing appropriate surveillance for these patients is central to managing the CRC risk in IBD. The increased risk of colorectal cancer in association with IBD is thought to be due to genetic and acquired factors. The link between inflammation and cancer is well recognised but the molecular biology, immune pathobiology and genetics of IBD-CRC are areas of much ongoing research. This review examines the literature relating to IBD-CRC, focusing on the incidence of IBD-CRC and examining potential risk factors including age at diagnosis, gender, duration and extent of colitis, severity of inflammation, family history of sporadic CRC and co-existent primary sclerosing cholangitis (PSC). Confirmed risk factors for IBD-CRC are duration, severity and extent of colitis, the presence of co-existent PSC and a family history of CRC. There is insufficient evidence currently to support an increased frequency of surveillance for patients diagnosed with IBD at a younger age. Evidence-based guidelines advise surveillance colonoscopy for patients with colitis 8 to 10 years after diagnosis, with the interval for further surveillance guided by risk factors (extent of disease, family history of CRC, post-inflammatory polyps, concomitant PSC, personal history of colonic dysplasia, colonic strictures). There is a move away from using random colonic biopsies towards targeted biopsies aimed at abnormal areas identified by newer colonoscopic techniques (narrow band imaging, chromoendoscopy, confocal microendoscopy).
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Dubé PE, Yan F, Punit S, Girish N, McElroy SJ, Washington MK, Polk DB. Epidermal growth factor receptor inhibits colitis-associated cancer in mice. J Clin Invest 2012; 122:2780-92. [PMID: 22772467 DOI: 10.1172/jci62888] [Citation(s) in RCA: 59] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/16/2012] [Accepted: 05/30/2012] [Indexed: 12/23/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic illness caused by complex interactions between genetic and environmental factors that propagate inflammation and damage to the gastrointestinal epithelium. This state of chronic inflammation increases the risk for development of colitis-associated cancer in IBD patients. Thus, the development of targeted therapeutics that can disrupt the cycle of inflammation and epithelial injury is highly attractive. However, such biological therapies, including those targeting epidermal growth factor receptor pathways, pose a risk of increasing cancer rates. Using two mouse models of colitis-associated cancer, we found that epidermal growth factor receptor inactivation accelerated the incidence and progression of colorectal tumors. By modulating inflammation and epithelial regeneration, epidermal growth factor receptor optimized the response to chronic inflammation and limited subsequent tumorigenesis. These findings provide important insights into the pathogenesis of colitis-associated cancer and suggest that epidermal growth factor-based therapies for IBD may reduce long-term cancer risk.
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Affiliation(s)
- Philip E Dubé
- The Saban Research Institute of Children’s Hospital Los Angeles, Los Angeles, CA, USA
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Goldstone R, Itzkowitz S, Harpaz N, Ullman T. Progression of low-grade dysplasia in ulcerative colitis: effect of colonic location. Gastrointest Endosc 2011; 74:1087-93. [PMID: 21907984 DOI: 10.1016/j.gie.2011.06.028] [Citation(s) in RCA: 44] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2011] [Accepted: 06/15/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND Emerging evidence suggests that the biology of sporadic colorectal neoplasia may differ between the proximal and distal colon. Whether such a difference exists in colitis-associated colorectal neoplasia is unknown. OBJECTIVE To compare the rate of progression to advanced neoplasia (AN) between proximal and distal dysplasia in patients with ulcerative colitis (UC). DESIGN Retrospective cohort study. SETTING Tertiary medical center. PATIENTS From an institutional database of more than 700 patients with UC who underwent 2 or more surveillance colonoscopies between 1994 and 2006, we identified patients with extensive UC and low-grade dysplasia (LGD). Neoplasia proximal to the splenic flexure was considered proximal. MAIN OUTCOME MEASUREMENT Progression to AN, defined as high-grade dysplasia (HGD) or colorectal cancer (CRC). RESULTS Among 121 patients with LGD, all 7 who progressed to CRC and 6 of 8 who progressed to HGD had distal LGD initially. Subjects with distal LGD had a significantly shorter time to progression than those with proximal LGD (P = .019); 5-year AN-free survivals for distal and proximal LGD were 75 ± 7% and 95 ± 3%, respectively (hazard ratio [HR] 5.0; 95% CI, 1.1-22.0). Additionally, flat LGD was significantly more likely to progress than raised LGD on univariate testing (HR 3.6; 95% CI, 1.3-10.1). Neither morphology nor sidedness remained significant in multivariable testing, although there was little change in the HRs (HR 2.4; 95% CI, 0.8-7.1 for morphology; HR 3.5; 95% CI, 0.7-16.8 for sidedness) in proportional hazards modeling. LIMITATIONS Nonrandomized, retrospective trial and low incidence of AN. CONCLUSIONS In patients with long-standing, extensive UC, distal LGD is more common and progresses more rapidly to AN than proximal LGD.
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Affiliation(s)
- Robert Goldstone
- The Dr. Henry D. Janowitz Division of Gastroenterology, The Mount Sinai School of Medicine, New York, New York 10029, USA
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Eaton JE, Silveira MG, Pardi DS, Sinakos E, Kowdley KV, Luketic VA, Harrison ME, McCashland T, Befeler AS, Harnois D, Jorgensen R, Petz J, Lindor KD. High-dose ursodeoxycholic acid is associated with the development of colorectal neoplasia in patients with ulcerative colitis and primary sclerosing cholangitis. Am J Gastroenterol 2011; 106:1638-45. [PMID: 21556038 PMCID: PMC3168684 DOI: 10.1038/ajg.2011.156] [Citation(s) in RCA: 182] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
OBJECTIVES Some studies have suggested that ursodeoxycholic acid (UDCA) may have a chemopreventive effect on the development of colorectal neoplasia in patients with ulcerative colitis (UC) and primary sclerosing cholangitis (PSC). We examined the effects of high-dose (28-30 mg/kg/day) UDCA on the development of colorectal neoplasia in patients with UC and PSC. METHODS Patients with UC and PSC enrolled in a prior, multicenter randomized placebo-controlled trial of high-dose UDCA were evaluated for the development of colorectal neoplasia. Patients with UC and PSC who received UDCA were compared with those who received placebo. We reviewed the pathology and colonoscopy reports for the development of low-grade or high-grade dysplasia or colorectal cancer. RESULTS Fifty-six subjects were followed for a total of 235 patient years. Baseline characteristics (including duration of PSC and UC, medications, patient age, family history of colorectal cancer, and smoking status) were similar for both the groups. Patients who received high-dose UDCA had a significantly higher risk of developing colorectal neoplasia (dysplasia and cancer) during the study compared with those who received placebo (hazard ratio: 4.44, 95% confidence interval: 1.30-20.10, P=0.02). CONCLUSIONS Long-term use of high-dose UDCA is associated with an increased risk of colorectal neoplasia in patients with UC and PSC.
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Affiliation(s)
- John E. Eaton
- Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Marina G. Silveira
- Department of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Darrell S. Pardi
- Department of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Emmanouil Sinakos
- Department of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Kris V. Kowdley
- Center for Liver Disease, Virginia Mason Medical Center, Seattle, Washington, USA
| | - Velimir A.C. Luketic
- Division of Gastroenterology, Hepatology, and Nutrition, Virginia Commonwealth University School of Medicine, Richmond, Virginia, USA
| | - M. Edwyn Harrison
- Division of Gastroenterology and Hepatology, Mayo Clinic, Scottsdale, Arizona, USA
| | - Timothy McCashland
- Department of Internal Medicine, University of Nebraska, Lincoln, Nebraska, USA
| | - Alex S. Befeler
- Division of Gastroenterology and Hepatology, Saint Louis University, St Louis, Missouri, USA
| | - Denise Harnois
- Division of Gastroenterology and Hepatology, Mayo Clinic, Jacksonville, Florida USA
| | - Roberta Jorgensen
- Department of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Jan Petz
- Department of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
| | - Keith D. Lindor
- Department of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, Minnesota, USA
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Mattar MC, Lough D, Pishvaian MJ, Charabaty A. Current management of inflammatory bowel disease and colorectal cancer. GASTROINTESTINAL CANCER RESEARCH : GCR 2011; 4:53-61. [PMID: 21673876] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Subscribe] [Scholar Register] [Received: 09/07/2009] [Accepted: 04/06/2010] [Indexed: 09/28/2022]
Abstract
INFLAMMATORY BOWEL DISEASES (IBDS) CAN BE DIVIDED INTO TWO MAJOR DISORDERS: ulcerative colitis and Crohn's disease. Although IBD-associated colorectal cancer (IBD-CRC) accounts for only 1-2% of all cases of colorectal cancer, IBD with colon involvement is among the top three high-risk conditions for colorectal cancer. Today, colorectal cancer accounts for approximately 10-15% of all deaths among IBD patients. Indeed, patients with IBD colitis are six times more likely to develop colorectal cancer than the general population and have a higher frequency of multiple synchronous colorectal cancers. Since IBD-CRC was first described in 1925, the colon remains the primary site of neoplasms in IBD patients today. Ulcerative colitis-associated colorectal cancer is most common in the rectum and sigmoid colon, whereas Crohn's disease-associated colorectal cancer is evenly distributed between the different colon segments. Chemoprevention of colorectal cancer remains an important goal, and colonoscopy surveillance programs are critical to early detection in these patients. Newer methods, such as chromoendoscopy, are currently being investigated as complementary techniques to enhance early detection of dysplasia and cancer in this high-risk population. We present a comprehensive review of the relationship between inflammatory bowel disease and colorectal cancer. Major themes covered include risk factors for IBD-CRC and the molecular pathobiology of progression from dysplasia to cancer, endoscopic surveillance and new methods for early detection of dysplasia, approaches to prevention of IBD-CRC, and current recommendations and controversies regarding the treatment of dysplasia. In particular, disagreement has arisen over optimal management of low-grade dysplasia, with some IBD experts now advocating close colonoscopic surveillance of patients with low-grade dysplasia rather then total colectomy.
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Söderlund S, Tribukait B, Öst Å, Broström O, Karlén P, Löfberg R, Askling J, Sjöqvist U. Colitis-associated DNA aneuploidy and dysplasia in Crohn's disease and risk of colorectal cancer. Inflamm Bowel Dis 2011; 17:1101-7. [PMID: 20853434 DOI: 10.1002/ibd.21477] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/31/2010] [Accepted: 08/03/2010] [Indexed: 12/09/2022]
Abstract
BACKGROUND There is uncertainty about how patients with Crohn's colitis should be monitored for colorectal cancer (CRC). By analogy to ulcerative colitis, regular colonoscopy with biopsies for dysplasia has been used. We describe the occurrence of dysplasia and DNA aneuploidy in a cohort of patients with Crohn's colitis. METHODS In all, 245 patients with extensive colitis (225 with a firm diagnosis of Crohn's disease, and 20 diagnosed as indeterminate colitis) at Stockholm Söder Hospital and Karolinska University Hospital, Huddinge were included. They were followed with regular colonoscopies with biopsies both for dysplasia and DNA aneuploidy. The cumulative occurrence of DNA aneuploidy and dysplasia was estimated using Kaplan-Meier curves. Time sequences and interactions between DNA aneuploidy, dysplasia, and CRC were studied using Cox regression analysis, adjusted for age, sex, and age at diagnosis. RESULTS During a median follow-up time of 9.2 person-years, DNA aneuploidy was found in 53 patients (22%), with 10 patients having multifocal aneuploidy and high S-phase values. Dysplasia was found in 42 patients (17%), 10 having multifocal dysplasia. Relative risk (RR) of dysplasia given DNA aneuploidy was 5.3 (95% confidence interval [CI] 2.3-12). RR of CRC given dysplasia was 10 (95% CI 2-50), and RR of CRC given aneuploidy was 1.5 (95% CI 0.3-9.3). CONCLUSIONS Dysplasia and DNA aneuploidy including S-phase analysis may complement stratification of patients with Crohn’s
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Affiliation(s)
- Sverre Söderlund
- Department of Medicine, Karolinska Institutet, Stockholm Söder Hospital, Stockholm, Sweden.
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Levesque BG, Hanson KA, Sandborn WJ. Reversal of multifocal low- and high-grade dysplasia in patients with an ileoanal pouch. Gastroenterology 2011; 140:1107-8; author reply 1108-9. [PMID: 21272556 DOI: 10.1053/j.gastro.2010.12.052] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/08/2010] [Accepted: 12/14/2010] [Indexed: 12/02/2022]
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Pekow JR, Hetzel JT, Rothe JA, Hanauer SB, Turner JR, Hart J, Noffsinger A, Huo D, Rubin DT. Outcome after surveillance of low-grade and indefinite dysplasia in patients with ulcerative colitis. Inflamm Bowel Dis 2010; 16:1352-6. [PMID: 20027656 PMCID: PMC3046461 DOI: 10.1002/ibd.21184] [Citation(s) in RCA: 56] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
BACKGROUND The management of low-grade (LGD) and indefinite dysplasia (IND) in patients with ulcerative colitis (UC) remains controversial, as outcomes after a diagnosis of LGD or IND in previous studies vary widely. METHODS All patients evaluated were from a single institution referral center who had a history of UC and a diagnosis of either LGD or IND between 1994 and 2008 as confirmed by 2 expert gastrointestinal (GI) pathologists. Data were collected by chart review of electronic and paper medical records. All patients who did not undergo a colectomy within 90 days of their dysplasia diagnosis were included in the final analysis. Hazard ratios for risk factors as well as incidence rates and Kaplan-Meier estimates were used to calculate the progression to high-grade dysplasia (HGD) or colorectal cancer (CRC). RESULTS Thirty-five patients were included in the analysis, of whom 2 patients with IND and 2 patients with LGD developed HGD or CRC over a mean duration of 49.8 months. In total, the incident rate for advanced neoplasia for all patients was 2.7 cases of HGD or CRC per 100 person-years at risk. For flat and polypoid LGD the incident rate of advanced neoplasia was 4.3 and 1.5 cases per 100 person-years at risk, respectively. Patients with primary sclerosing cholangitis (PSC) had an incident rate of 10.5 cases per 100 years of patient follow-up. CONCLUSIONS We report a low rate of progression to HGD or CRC in patients who underwent surveillance for LGD or IND; polypoid dysplasia showed less risk of progression than flat dysplasia.
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Affiliation(s)
- Joel R. Pekow
- University of Chicago, Section of Gastroenterology, Hepatology, and Nutrition, Chicago, Illinois
| | - Jeremy T. Hetzel
- University of Chicago, Section of Gastroenterology, Hepatology, and Nutrition, Chicago, Illinois
| | - Jami A. Rothe
- University of Chicago, Section of Gastroenterology, Hepatology, and Nutrition, Chicago, Illinois
| | - Stephen B. Hanauer
- University of Chicago, Section of Gastroenterology, Hepatology, and Nutrition, Chicago, Illinois
| | | | - John Hart
- University of Chicago, Department of Pathology, Chicago, Illinois
| | - Amy Noffsinger
- University of Chicago, Department of Pathology, Chicago, Illinois
| | - Dezheng Huo
- University of Chicago, Department of Health Studies, Chicago, Illinois
| | - David T. Rubin
- University of Chicago, Section of Gastroenterology, Hepatology, and Nutrition, Chicago, Illinois
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