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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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Del Chierico F, Cardile S, Baldelli V, Alterio T, Reddel S, Bramuzzo M, Knafelz D, Lega S, Bracci F, Torre G, Maggiore G, Putignani L. Characterization of the Gut Microbiota and Mycobiota in Italian Pediatric Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis. Inflamm Bowel Dis 2024; 30:529-537. [PMID: 37696680 PMCID: PMC10988104 DOI: 10.1093/ibd/izad203] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2023] [Indexed: 09/13/2023]
Abstract
BACKGROUND Primary sclerosing cholangitis (PSC) is a chronic, fibroinflammatory, cholestatic liver disease of unknown etiopathogenesis, often associated with inflammatory bowel diseases. Recent evidence ascribes, together with immunologic and environmental components, a significant role to the intestinal microbiota or its molecules in the PSC pathogenesis. METHODS By metagenomic sequencing of 16S rRNA and ITS2 loci, we describe the fecal microbiota and mycobiota of 26 pediatric patients affected by PSC and concomitant ulcerative colitis (PSC-UC), 27 patients without PSC but with UC (UC), and 26 healthy subjects (CTRLs). RESULTS Compared with CTRL, the bacterial and fungal gut dysbiosis was evident for both PSC-UC and UC groups; in particular, Streptococcus, Saccharomyces, Sporobolomyces, Tilletiopsis, and Debaryomyces appeared increased in PSC-UC, whereas Klebsiella, Haemophilus, Enterococcus Collinsella, Piptoporus, Candida, and Hyphodontia in UC. In both patient groups, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma and Malassezia were decreased. Co-occurrence analysis evidenced the lowest number of nodes and edges for fungi networks compared with bacteria. Finally, we identified a specific patient profile, based on liver function tests, bacterial and fungal signatures, that is able to distinguish PSC-UC from UC patients. CONCLUSIONS We describe the gut microbiota and mycobiota dysbiosis associated to PSC-UC disease. Our results evidenced a gut imbalance, with the reduction of gut commensal microorganisms with stated anti-inflammatory properties (ie, Akkermansia, Bacteroides, Parabacteroides, Oscillospira, Meyerozyma, and Malassezia) and the increase of pathobionts (ie, Streptococcus, Saccharomyces, and Debaryomyces) that could be involved in PSC progression. Altogether, these events may concur in the pathophysiology of PSC in the framework of UC.
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Affiliation(s)
- Federica Del Chierico
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
| | - Sabrina Cardile
- Hepatology, Gastroenterology, Nutrition and Liver transplantation Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy
| | - Valerio Baldelli
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
| | - Tommaso Alterio
- Hepatology, Gastroenterology, Nutrition and Liver transplantation Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy
| | - Sofia Reddel
- Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
| | - Matteo Bramuzzo
- Gastroenterology, Digestive Endoscopy and Nutrition Unit, Institute for Maternal and Child Health, IRCCS “Burlo Garofolo,”Trieste, Italy
| | - Daniela Knafelz
- Hepatology, Gastroenterology, Nutrition and Liver transplantation Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy
| | - Sara Lega
- Gastroenterology, Digestive Endoscopy and Nutrition Unit, Institute for Maternal and Child Health, IRCCS “Burlo Garofolo,”Trieste, Italy
| | - Fiammetta Bracci
- Hepatology, Gastroenterology, Nutrition and Liver transplantation Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy
| | - Giuliano Torre
- Hepatology, Gastroenterology, Nutrition and Liver transplantation Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy
| | - Giuseppe Maggiore
- Hepatology, Gastroenterology, Nutrition and Liver transplantation Unit, Bambino Gesù Children’s Hospital IRCCS, Rome, Italy
| | - Lorenza Putignani
- Unit of Microbiology and Diagnostic Immunology, Unit of Microbiomics and Immunology, Rheumatology and Infectious Diseases Research Area, Unit of Human Microbiome, Bambino Gesù Children’s Hospital, IRCCS, Rome, Italy
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3
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Singh A, Midha V, Narang V, Kedia S, Mahajan R, Dhoble P, Kahlon BK, Dhaliwal AS, Tripathi A, Kalra S, Jain NP, Bansal N, Banerjee R, Desai D, Dutta U, Ahuja V, Sood A. Low prevalence of primary sclerosing cholangitis in patients with inflammatory bowel disease in India. Intest Res 2023; 21:452-459. [PMID: 36453008 PMCID: PMC10626019 DOI: 10.5217/ir.2022.00087] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 09/14/2022] [Accepted: 09/19/2022] [Indexed: 12/03/2022] Open
Abstract
BACKGROUND/AIMS Primary sclerosing cholangitis (PSC) represents the most common hepatobiliary extraintestinal manifestation of inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn's disease (CD). Limited data exist on PSC in patients with IBD from India. We aimed to assess the prevalence and disease spectrum of PSC in Indian patients with IBD. METHODS Database of IBD patients at 5 tertiary care IBD centers in India were analyzed retrospectively. Data were extracted and the prevalence of PSC-IBD was calculated. RESULTS Forty-eight patients out of 12,216 patients with IBD (9,231 UC, 2,939 CD, and 46 IBD unclassified) were identified to have PSC, resulting in a prevalence of 0.39%. The UC to CD ratio was 7:1. Male sex and pancolitis (UC) or colonic CD were more commonly associated with PSC-IBD. The diagnosis of IBD preceded the diagnosis of PSC in most of the patients. Majority of the patients were symptomatic for liver disease at diagnosis. Eight patients (16.66%) developed cirrhosis, 5 patients (10.41%), all UC, developed malignancies (3 colorectal cancer [6.25%] and 2 cholangiocarcinoma [4.16%]), and 3 patients died (2 decompensated liver disease [4.16%] and 1 cholangiocarcinoma [2.08%]) on follow-up. None of the patients mandated surgical therapy for IBD. CONCLUSIONS Concomitant PSC in patients with IBD is uncommon in India and is associated with lower rates of development of malignancies.
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Affiliation(s)
- Arshdeep Singh
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Vandana Midha
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, India
| | - Vikram Narang
- Department of Pathology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Saurabh Kedia
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Ramit Mahajan
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Pavan Dhoble
- P. D. Hinduja National Hospital and Medical Research Centre, Mumbai, India
| | - Bhavjeet Kaur Kahlon
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Ashvin Singh Dhaliwal
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Ashish Tripathi
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Shivam Kalra
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Narender Pal Jain
- Department of Internal Medicine, Dayanand Medical College and Hospital, Ludhiana, India
| | - Namita Bansal
- Research and Development Centre, Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
| | - Rupa Banerjee
- Asian Institute of Gastroenterology, Hyderabad, India
| | - Devendra Desai
- P. D. Hinduja National Hospital and Medical Research Centre, Mumbai, India
| | - Usha Dutta
- Department of Gastroenterology, Postgraduate Institute of Medical Education and Research, Chandigarh, India
| | - Vineet Ahuja
- Department of Gastroenterology, All India Institute of Medical Sciences, New Delhi, India
| | - Ajit Sood
- Department of Gastroenterology, Dayanand Medical College and Hospital, Ludhiana, India
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Shen B. Interventional inflammatory bowel disease: endoscopic therapy of complications of Crohn's disease. Gastroenterol Rep (Oxf) 2022; 10:goac045. [PMID: 36120488 PMCID: PMC9472786 DOI: 10.1093/gastro/goac045] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2022] [Accepted: 08/15/2022] [Indexed: 11/25/2022] Open
Abstract
Endoscopic therapy for inflammatory bowel diseases (IBD) or IBD surgery-associated complications or namely interventional IBD has become the main treatment modality for Crohn’s disease, bridging medical and surgical treatments. Currently, the main applications of interventional IBD are (i) strictures; (ii) fistulas and abscesses; (iii) bleeding lesions, bezoars, foreign bodies, and polyps; (iv) post-operative complications such as acute and chronic anastomotic leaks; and (v) colitis-associated neoplasia. The endoscopic treatment modalities include balloon dilation, stricturotomy, strictureplasty, fistulotomy, incision and drainage (of fistula and abscess), sinusotomy, septectomy, banding ligation, clipping, polypectomy, endoscopic mucosal resection, and endoscopic submucosal dissection. The field of interventional IBD is evolving with a better understanding of the underlying disease process, advances in endoscopic technology, and interest and proper training of next-generation IBD interventionalists.
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Affiliation(s)
- Bo Shen
- Center for Inflammatory Bowel Disease, Columbia University Irving Medical Center/New York-Presbyterian Hospital, New York, NY, USA
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5
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Friedberg S, Rubin DT. Intestinal Cancer and Dysplasia in Crohn's Disease. Gastroenterol Clin North Am 2022; 51:369-379. [PMID: 35595420 DOI: 10.1016/j.gtc.2021.12.011] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
Crohn's disease is associated with an increased risk of adenocarcinoma of the involved portions of the small bowel and colorectum and has similar risk factors to those described in ulcerative colitis, most significantly, extent of bowel involvement, PSC, and duration of unresected disease. Prevention strategies include risk stratification and secondary prevention with colonoscopic screening and surveillance to identify dysplasia or early-stage cancers, with surgery when needed. There is emerging information to suggest that control of inflammation may provide primary prevention of neoplasia, but further studies are required to test this strategy.
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Affiliation(s)
- Scott Friedberg
- University of Chicago Medicine Inflammatory Bowel Disease Center
| | - David T Rubin
- University of Chicago Medicine Inflammatory Bowel Disease Center.
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6
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Losurdo G, Brescia IV, Lillo C, Mezzapesa M, Barone M, Principi M, Ierardi E, Di Leo A, Rendina M. Liver involvement in inflammatory bowel disease: What should the clinician know? World J Hepatol 2021; 13:1534-1551. [PMID: 34904028 PMCID: PMC8637677 DOI: 10.4254/wjh.v13.i11.1534] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/25/2021] [Revised: 05/06/2021] [Accepted: 10/11/2021] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD) may show a wide range of extraintestinal manifestations. In this context, liver involvement is a focal point for both an adequate management of the disease and its prognosis, due to possible serious comorbidity. The association between IBD and primary sclerosing cholangitis is the most known example. This association is relevant because it implies an increased risk of both colorectal cancer and cholangiocarcinoma. Additionally, drugs such as thiopurines or biologic agents can cause drug-induced liver damage; therefore, this event should be considered when planning IBD treatment. Additionally, particular consideration should be given to the evidence that IBD patients may have concomitant chronic viral hepatitis, such as hepatitis B and hepatitis C. Chronic immunosuppressive regimens may cause a hepatitis flare or reactivation of a healthy carrier state, therefore careful monitoring of these patients is necessary. Finally, the spread of obesity has involved even IBD patients, thus increasing the risk of non-alcoholic fatty liver disease, which has already proven to be more common in IBD patients than in the non-IBD population. This phenomenon is considered an emerging issue, as it will become the leading cause of liver cirrhosis.
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Affiliation(s)
- Giuseppe Losurdo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy.
| | - Irene Vita Brescia
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Chiara Lillo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Martino Mezzapesa
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Michele Barone
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Mariabeatrice Principi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Enzo Ierardi
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Alfredo Di Leo
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
| | - Maria Rendina
- Section of Gastroenterology, Department of Emergency and Organ Transplantation, University of Bari, Bari 70124, Italy
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7
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Attauabi M, Zhao M, Bendtsen F, Burisch J. Systematic review and meta-analysis: the impact of co-occurring immune-mediated inflammatory diseases on the disease localization and behavior of Crohn's disease. Therap Adv Gastroenterol 2021; 14:17562848211004839. [PMID: 34234844 PMCID: PMC8226240 DOI: 10.1177/17562848211004839] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Accepted: 03/04/2021] [Indexed: 02/04/2023] Open
Abstract
BACKGROUND Patients with Crohn's disease (CD) are at increased risk of co-occurring immune-mediated inflammatory diseases (IMIDs). As discrepancy exists regarding the phenotypic presentation of CD among patients with such co-occurring IMIDs, we aimed to conduct a systematic review with meta-analysis characterizing the phenotype of CD among this subgroup of patients. METHODS PubMed, Embase, and Scopus were searched from their earliest records to October 2019 for studies reporting the behavior and localization of CD according to the Vienna or Montreal Classifications and CD-related surgery in patients with co-occurring IMIDs. These studies were the subject of a random effect meta-analysis. RESULTS After reviewing 24,413 studies, we identified a total of 23 studies comprising 1572 and 35,043 CD patients with and without co-occurring IMIDs, respectively, that fulfilled our inclusion criteria. Overall, patients with co-occurring IMIDs were more likely to have upper gastrointestinal inflammation than were patients without co-occurring IMIDs [relative risk (RR) = 1.49 (95% confidence interval (CI) 1.09-2.04), p = 0.01, I 2 = 7%]. In addition, presence of primary sclerosing cholangitis (PSC) was associated with a lower occurrence of ileal affection [RR = 0.44 (95% CI 0.24-0.81), p < 0.01, I 2 = 32%], increased occurrence of colonic affection [RR = 1.78 (95% CI 1.33-2.38), p < 0.01, I 2 = 32%] and an increased likelihood of non-stricturing and non-penetrating behavior [RR = 1.43 (95% CI 0.97-2.11), p = 0.07, I 2 = 86%]. The latter reached significance when cumulating different IMIDs [RR = 1.30 (95% CI 1.09-1.55), p < 0.01, I 2 = 88%]. CD patients with PSC also underwent fewer CD-related surgeries [RR = 0.55 (95% CI 0.34-0.88), p = 0.01, I 2 = 0%], irrespective of CD location or behavior. CONCLUSION This study emphasizes that CD patients with co-existing PSC are likely to have a unique inflammatory distribution primarily confined to the colon, while patients with IMIDs in general have higher likelihood of affection of upper gastrointestinal tract and a non-stricturing and non-penetrating behavior. As such a phenotype of CD is typically associated with a milder disease course; future studies are needed to confirm these results.
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Affiliation(s)
- Mohamed Attauabi
- Gastrounit, Medical Section, Copenhagen
University Hospital Hvidovre, Kettegaard Alle 30, Denmark
- Copenhagen Center for Inflammatory Bowel
Disease in Children, Adolescents and Adults, University of Copenhagen,
Hvidovre Hospital, Denmark
| | - Mirabella Zhao
- Gastrounit, Medical Section, Copenhagen
University Hospital, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel
Disease in Children, Adolescents and Adults, University of Copenhagen,
Hvidovre Hospital, Denmark
| | - Flemming Bendtsen
- Gastrounit, Medical Section, Copenhagen
University Hospital, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel
Disease in Children, Adolescents and Adults, University of Copenhagen,
Hvidovre Hospital, Denmark
| | - Johan Burisch
- Gastrounit, Medical Section, Copenhagen
University Hospital, Hvidovre, Denmark
- Copenhagen Center for Inflammatory Bowel
Disease in Children, Adolescents and Adults, University of Copenhagen,
Hvidovre Hospital, Denmark
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Alkhayyat M, Abureesh M, Gill A, Khoudari G, Abou Saleh M, Mansoor E, Regueiro M. Lower Rates of Colorectal Cancer in Patients With Inflammatory Bowel Disease Using Anti-TNF Therapy. Inflamm Bowel Dis 2021; 27:1052-1060. [PMID: 33051651 DOI: 10.1093/ibd/izaa252] [Citation(s) in RCA: 36] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/27/2020] [Indexed: 12/12/2022]
Abstract
BACKGROUND Chronic inflammation is a key factor for the development of colorectal cancer (CRC) among patients with inflammatory bowel disease (IBD). Despite the increased use of biologic agents in patients with IBD, their impact on colorectal carcinogenesis remains unclear. With the use of a large database, we sought to describe the effect of biologics on CRC among patients with IBD. METHODS We evaluated a multicenter database (Explorys) consisting of electronic medical records from several U.S. hospitals between 1999 and 2020. A cohort of patients with a diagnosis of IBD was identified. We performed a multivariate analysis to adjust for multiple factors including medical and surgical therapies. RESULTS There were a total of 62,007,510 patients in the database between 1999 and 2020. Amongst those, 225,090 (0.36%) individuals had Crohn's disease and 188,420 (0.30%) had ulcerative colitis. After adjusting for confounding factors using multivariate analysis, patients with IBD were more likely to develop CRC. Among the IBD cohort, patients treated with anti-TNF agents were less likely to develop CRC; patients with Crohn's disease: odds ratio, 0.69; 95% confidence interval, 0.66-0.73; P < 0.0001 vs patients with ulcerative colitis: odds ratio, 0.78; 95% confidence interval, 0.73-0.83; P < 0.0001. CONCLUSIONS Patients with IBD who were treated with anti-tumor necrosis factor agents were less likely to develop CRC. Prospective studies are needed to evaluate whether anti-tumor necrosis factor drugs provide a chemoprotective effect in patients with IBD by inflammation control and mucosal healing.
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Affiliation(s)
- Motasem Alkhayyat
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Mohammad Abureesh
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, New York, USA
| | - Arshpal Gill
- Department of Internal Medicine, Staten Island University Hospital, Staten Island, New York, USA
| | - George Khoudari
- Department of Hospital Medicine, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Mohannad Abou Saleh
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic Foundation, Cleveland, Ohio, USA
| | - Emad Mansoor
- Department of Gastroenterology and Liver Disease, Case Western Reserve University/University Hospitals, Cleveland, Ohio, USA
| | - Miguel Regueiro
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic Foundation, Cleveland, Ohio, USA
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9
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Rocha HC, Vilela EG. Clinical aspects and prognosis of patients with inflammatory bowel disease associated with autoimmune liver diseases. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 45:83-90. [PMID: 34023469 DOI: 10.1016/j.gastrohep.2021.03.011] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/01/2020] [Revised: 01/29/2021] [Accepted: 03/15/2021] [Indexed: 01/07/2023]
Abstract
BACKGROUND AND AIMS Inflammatory bowel diseases (IBD) are chronic conditions that may be accompanied by autoimmune liver disease (AILD), most commonly primary sclerosing cholangitis (PSC). The objective of this study was to evaluate the behaviour of patients with IBD associated with AILD and compare a PSC group with a non-PSC group. METHODS Medical records of patients with IBD associated with PSC, autoimmune cholangitis, primary biliary cholangitis, small-duct PSC, autoimmune hepatitis (AIH) and overlapping syndromes were assessed. RESULTS Fifty-four patients were included: 48 (88.9%) had ulcerative colitis and six (11.1%) had Crohn's disease; 35 (64.8%) had PSC and 19 (35.2%) did not have PSC. There was no difference in outcomes (surgical treatment for IBD, liver transplantation or death) between the groups. Time since the diagnosis of IBD was associated with surgical treatment of IBD (p=0.041; OR: 1.139, 95% CI: 1.006-1.255). Time since the diagnosis of AILD (p=0.003; OR: 1.259, 95% CI: 1.1-1.396), as well as portal hypertension at diagnosis (p=0.014; OR: 18.22, 95% CI: 1.815-182.96), were associated with liver transplantation. In addition, previous diagnosis of AIH was associated with de novo IBD (p=0.012; OR: 7.1, 95% CI: 1.215-42.43). CONCLUSION Both groups had similar disease behaviour. A longer time since the diagnosis of IBD increased the risk for surgical treatment (13.9%/year). A 25.9%/year increase in liver transplantation was observed after the diagnosis of AILD, which was increased 18.22 times by the presence of portal hypertension. In addition, the diagnosis of AIH was associated with an increase in the number of diagnoses of de novo IBD (7.1).
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Affiliation(s)
- Henrique C Rocha
- Alfa Institute of Gastroenterology - Hospital das Clínicas da Universidade Federal de Minas Gerais, Brazil.
| | - Eduardo G Vilela
- Alfa Institute of Gastroenterology - Hospital das Clínicas da Universidade Federal de Minas Gerais, Brazil
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10
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Attauabi M, Zhao M, Bendtsen F, Burisch J. Systematic Review with Meta-analysis: The Impact of Co-occurring Immune-mediated Inflammatory Diseases on the Disease Course of Inflammatory Bowel Diseases. Inflamm Bowel Dis 2021; 27:927-939. [PMID: 32628745 DOI: 10.1093/ibd/izaa167] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/12/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS Patients with inflammatory bowel diseases (IBDs) are at risk of developing a variety of other immune-mediated inflammatory diseases (IMIDs). The influence of co-occurring IMIDs on the disease course of IBD remains unknown. The aim of this study was therefore to conduct a systematic review and meta-analysis of the impact of IMIDs on phenotypic presentation and outcome in patients with IBD. METHODS PubMed and Embase were searched from their earliest records through December 2018 and updated in October 2019 for studies reporting proportions or ratios of IBD-related disease outcomes in patients with and without co-occurring IMIDs. Meta-analyses were performed to estimate summary proportions and risks of the main outcomes. PRISMA guidelines were used, and study quality was assessed according to the Newcastle-Ottawa Scale. RESULTS A total of 93 studies were identified, comprising 16,064 IBD patients with co-occurring IMIDs and 3,451,414 IBD patients without IMIDs. Patients with IBD and co-occurring IMIDs were at increased risk of having extensive colitis or pancolitis (risk ratio, 1.38; 95% Cl, 1.25-1.52; P < 0.01, I2 = 86%) and receiving IBD-related surgeries (risk ratio, 1.17; 95% Cl, 1.01-1.36; P = 0.03; I2 = 85%) compared with patients without IMIDs. Co-occurrence of IMIDs other than primary sclerosing cholangitis in patients with IBD was associated with an increased risk of receiving immunomodulators (risk ratio, 1.15; 95% Cl, 1.06-1.24; P < 0.01; I2 = 60%) and biologic therapies (risk ratio, 1.19; 95% Cl, 1.08-1.32; P < 0.01; I2 = 53%). CONCLUSION This meta-analysis found that the presence of co-occurring IMIDs influences the disease course of IBD, including an increased risk of surgery and its phenotypical expression.
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Affiliation(s)
- Mohamed Attauabi
- Gastrounit, Medical Division, Copenhagen University Hospital, Hvidovre, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Mirabella Zhao
- Gastrounit, Medical Division, Copenhagen University Hospital, Hvidovre, Denmark
| | - Flemming Bendtsen
- Gastrounit, Medical Division, Copenhagen University Hospital, Hvidovre, Denmark.,Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark
| | - Johan Burisch
- Gastrounit, Medical Division, Copenhagen University Hospital, Hvidovre, Denmark
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11
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Bury MI, Fuller NJ, Clemons TD, Sturm RM, Morrison CD, Lisy‐Snow DC, Nolan BG, Tarczynski C, Ayello EMT, Boyce A, Muckian B, Ahmad N, Hunter CJ, Karver MR, Stupp SI, Sharma AK. Self‐Assembling Nanofibers Inhibit Inflammation in a Murine Model of Crohn's‐Disease‐Like Ileitis. ADVANCED THERAPEUTICS 2021. [DOI: 10.1002/adtp.202000274] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/17/2022]
Affiliation(s)
- Matthew I. Bury
- Simpson Querrey Institute (SQI) Northwestern University 303 East Superior Street Chicago IL 60611 USA
- Lurie Children's Hospital of Chicago 255 East Superior Street Chicago IL 60611 USA
| | - Natalie J. Fuller
- Simpson Querrey Institute (SQI) Northwestern University 303 East Superior Street Chicago IL 60611 USA
- Lurie Children's Hospital of Chicago 255 East Superior Street Chicago IL 60611 USA
| | - Tristan D. Clemons
- Simpson Querrey Institute (SQI) Northwestern University 303 East Superior Street Chicago IL 60611 USA
- Department of Chemistry Northwestern University 2145 Sheridan Road Evanston IL 60208 USA
| | - Renea M. Sturm
- Department of Urology University of California Los Angeles 200 Medical Plaza Driveway #140 Los Angeles CA 90095 USA
| | - Christopher D. Morrison
- Department of Urology Northwestern University Feinberg School of Medicine 676 North St. Clair Suite 2300 Chicago IL 60611 USA
| | - Devon C. Lisy‐Snow
- Simpson Querrey Institute (SQI) Northwestern University 303 East Superior Street Chicago IL 60611 USA
- Lurie Children's Hospital of Chicago 255 East Superior Street Chicago IL 60611 USA
| | - Bonnie G. Nolan
- Simpson Querrey Institute (SQI) Northwestern University 303 East Superior Street Chicago IL 60611 USA
- Lurie Children's Hospital of Chicago 255 East Superior Street Chicago IL 60611 USA
| | - Christopher Tarczynski
- Simpson Querrey Institute (SQI) Northwestern University 303 East Superior Street Chicago IL 60611 USA
| | - Emily M. T. Ayello
- Simpson Querrey Institute (SQI) Northwestern University 303 East Superior Street Chicago IL 60611 USA
| | - Amber Boyce
- Simpson Querrey Institute (SQI) Northwestern University 303 East Superior Street Chicago IL 60611 USA
- Lurie Children's Hospital of Chicago 255 East Superior Street Chicago IL 60611 USA
| | - Bridget Muckian
- Simpson Querrey Institute (SQI) Northwestern University 303 East Superior Street Chicago IL 60611 USA
- Lurie Children's Hospital of Chicago 255 East Superior Street Chicago IL 60611 USA
| | - Nida Ahmad
- Simpson Querrey Institute (SQI) Northwestern University 303 East Superior Street Chicago IL 60611 USA
- Lurie Children's Hospital of Chicago 255 East Superior Street Chicago IL 60611 USA
| | - Catherine J. Hunter
- Simpson Querrey Institute (SQI) Northwestern University 303 East Superior Street Chicago IL 60611 USA
- Lurie Children's Hospital of Chicago 255 East Superior Street Chicago IL 60611 USA
| | - Mark R. Karver
- Simpson Querrey Institute (SQI) Northwestern University 303 East Superior Street Chicago IL 60611 USA
| | - Samuel I. Stupp
- Simpson Querrey Institute (SQI) Northwestern University 303 East Superior Street Chicago IL 60611 USA
- Department of Chemistry Northwestern University 2145 Sheridan Road Evanston IL 60208 USA
- McCormick School of Engineering Department of Biomedical Engineering Northwestern University 2145 Sheridan Road Evanston IL 60208 USA
- Department of Materials Science and Engineering Northwestern University 2145 Sheridan Road Evanston IL 60208 USA
- Feinberg School of Medicine Department of Medicine Northwestern University 420 E Superior Street Chicago IL 60611 USA
| | - Arun K. Sharma
- Simpson Querrey Institute (SQI) Northwestern University 303 East Superior Street Chicago IL 60611 USA
- Department of Urology Northwestern University Feinberg School of Medicine 676 North St. Clair Suite 2300 Chicago IL 60611 USA
- McCormick School of Engineering Department of Biomedical Engineering Northwestern University 2145 Sheridan Road Evanston IL 60208 USA
- Stanley Manne Children's Research Institute (SMCRI) 303 East Superior Street Chicago IL 60611 USA
- Center for Advanced Regenerative Engineering (CARE) 2145 Sheridan Road Evanston IL 60208 USA
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12
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Recommendations of the Spanish Working Group on Crohn's disease and Ulcerative Colitis (Grupo Español de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa - GETECCU) on dysplasia screening in inflammatory bowel disease patients. GASTROENTEROLOGIA Y HEPATOLOGIA 2021; 44:435-447. [PMID: 33592179 DOI: 10.1016/j.gastrohep.2020.12.011] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 12/21/2020] [Indexed: 12/12/2022]
Abstract
Colonic inflammatory bowel diseases have a higher risk of developing colorectal cancer compared to the general population, which is why they require endoscopic screening techniques with specific follow-up intervals based on the different risk factors described on the literature. This position paper analyzes the current scientific evidence for the different endoscopic techniques available today, how their implementation should be carried out in endoscopic units and describes in detail how their implementation should be carried out, in which patients and with what interval, and finally, what should be the response to finding dysplasia, proposing a specific follow-up algorithm.
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13
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Engin O, Kilinc G, Salimoglu S. Trends, Risk Factors, and Preventions in Colorectal Cancer. COLON POLYPS AND COLORECTAL CANCER 2021:213-233. [DOI: 10.1007/978-3-030-57273-0_10] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
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14
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Abstract
Crohn's disease is associated with various intestinal and extraintestinal malignancies. This article reviews the current literature regarding Crohn's disease and subsequent risk of cancer formation. Recognition of risk factors (both modifiable and unmodifiable) is essential for prevention and appropriate screening. Future investigations into the molecular mechanisms associated with Crohn-related malignancy will provide additional insight into carcinogenesis, potential for early intervention, and identification of at-risk patients.
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Affiliation(s)
- Evie Carchman
- Department of Surgery, University of Wisconsin, Madison, Wisconsin
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15
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Marya NB, Tabibian JH. Role of endoscopy in the management of primary sclerosing cholangitis. World J Gastrointest Endosc 2019; 11:84-94. [PMID: 30788027 PMCID: PMC6379747 DOI: 10.4253/wjge.v11.i2.84] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/28/2018] [Revised: 01/15/2019] [Accepted: 01/30/2019] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a rare but prominent fibroinflammatory cholangiopathy which can affect individuals of essentially any age. It carries a median survival of 15-20 years, regardless of age at diagnosis, and is a foremost risk factor for cholangiocarcinoma. Given the chronic and progressive nature of PSC, its inherent risk for biliary tract and other complications, and the paucity of effective pharmacotherapies, endoscopy plays a major role in the care of many patients with this disorder. In this review, we discuss the endoscopic management of PSC, including established and evolving approaches to the diagnosis and treatment of its benign as well as malignant sequelae. Owing to the rarity of PSC and dearth of high-quality evidence, we propose pragmatic approaches based on both currently available data and expert opinion.
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Affiliation(s)
- Neil Bharat Marya
- Vatche and Tamar Manoukian Division of Digestive Diseases, UCLA Gastroenterology Fellowship Training Program, Los Angeles, CA 90095, United States
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
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16
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Fung BM, Lindor KD, Tabibian JH. Cancer risk in primary sclerosing cholangitis: Epidemiology, prevention, and surveillance strategies. World J Gastroenterol 2019; 25:659-671. [PMID: 30783370 PMCID: PMC6378537 DOI: 10.3748/wjg.v25.i6.659] [Citation(s) in RCA: 59] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/30/2018] [Revised: 01/10/2019] [Accepted: 01/14/2019] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease characterized by progressive fibroinflammatory destruction of the intra- and/or extrahepatic biliary ducts. While its features and disease course can be variable, most patients with PSC have concurrent inflammatory bowel disease and will eventually develop liver cirrhosis and end-stage liver disease, with liver transplantation representing the only potentially curative option. Importantly, PSC is associated with a significantly increased risk of malignancy compared to the general population, mainly cholangiocarcinoma, gallbladder carcinoma, hepatocellular carcinoma, and colorectal cancer, with nearly 50% of deaths in patients with PSC being due to cancer. Therefore, robust surveillance strategies are needed, though uncertainty remains regarding how to best do so. In this review, we discuss the epidemiology, prevention, and surveillance of cancers in patients with PSC. Where evidence is limited, we present pragmatic approaches based on currently available data and expert opinion.
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Affiliation(s)
- Brian M Fung
- UCLA-Olive View Internal Medicine Residency Program, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
| | - Keith D Lindor
- Office of the University Provost, Arizona State University, Phoenix, AZ 85004, United States
| | - James H Tabibian
- Division of Gastroenterology, Department of Medicine, Olive View-UCLA Medical Center, Sylmar, CA 91342, United States
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17
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Fousekis FS, Theopistos VI, Mitselos IV, Skamnelos A, Kavvadias A, Katsanos KH, Christodoulou DK. Specific Features of Patients With Inflammatory Bowel Disease and Primary Sclerosing Cholangitis. J Clin Med Res 2019; 11:81-88. [PMID: 30700999 PMCID: PMC6340671 DOI: 10.14740/jocmr3680] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Accepted: 11/20/2018] [Indexed: 12/12/2022] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic and progressive disease of the biliary tract. PSC is strongly associated with inflammatory bowel disease (IBD), mainly with ulcerative colitis, and most PSC patients have underlying IBD. The pathophysiological interactions between IBD and PSC are unclear, although it seems that the patients with IBD and PSC have a distinct phenotype. IBD with coexisting PSC is more extensive and is characterized by milder activity compared to IBD alone. The coexistence of PSC increases the risk for colorectal cancer in IBD patients and lifelong annual surveillance colonoscopy is recommended. Also, liver transplantation (LT) for PSC may affect the course of IBD. In addition, the management of IBD after LT includes many specific problems. On the other hand, the effect of IBD on the natural history of PSC appears to be milder. However, IBD may increase the risk of postsurgical complications after LT and is a risk factor for recurrent PSC after LT. Overall, the coexistence of IBD with PSC changes the management, natural history and prognosis of both diseases.
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Affiliation(s)
- Fotios S. Fousekis
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Vasileios I. Theopistos
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Ioannis V. Mitselos
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Alexandros Skamnelos
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Athanasios Kavvadias
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Konstantinos H. Katsanos
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
| | - Dimitrios K. Christodoulou
- Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina, Greece
- Corresponding Author: Dimitrios K. Christodoulou, Department of Gastroenterology and Hepatology, Faculty of Medicine, University of Ioannina, Ioannina 45100, Greece.
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18
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Mertz A, Nguyen NA, Katsanos KH, Kwok RM. Primary sclerosing cholangitis and inflammatory bowel disease comorbidity: an update of the evidence. Ann Gastroenterol 2019; 32:124-133. [PMID: 30837784 PMCID: PMC6394256 DOI: 10.20524/aog.2019.0344] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/17/2018] [Accepted: 11/29/2018] [Indexed: 12/12/2022] Open
Abstract
Comorbid primary sclerosing cholangitis (PSC) and inflammatory bowel disease (IBD) represent a unique disease phenotype with a different risk profile than PSC or IBD alone. While the pathogenetic mechanisms behind both diseases remain unclear, recent studies have targeted several immune-mediated pathways in an attempt to find a potential therapeutic target. Patients with PSC-associated IBD typically exhibit pancolitis with a right-to-left intestinal inflammatory gradient associated with a greater incidence of backwash ileitis and rectal sparing. Although there is an increased incidence of pancolitis in this population, bowel symptoms tend to be less significant than in IBD alone. Likewise, the degree of inflammation and symptoms of PSC-associated IBD are characteristically less clinically significant. Despite the relatively quiescent clinical presentation of PSC-associated IBD, there is an increased risk for colorectal and hepatobiliary malignancy making vigilance for malignancy essential.
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Affiliation(s)
- Andrew Mertz
- Department of Internal Medicine (Andrew Mertz), Walter Reed National Military Medical Center Bethesda, MD, USA
| | - Nhu An Nguyen
- Gastroenterology (Nhu An Nguyen, Ryan M. Kwok), Walter Reed National Military Medical Center Bethesda, MD, USA
| | - Konstantinos H Katsanos
- Gastroenterology, Medical School and University Hospital of Ioannina, Greece (Konstantinos H. Katsanos)
| | - Ryan M Kwok
- Gastroenterology (Nhu An Nguyen, Ryan M. Kwok), Walter Reed National Military Medical Center Bethesda, MD, USA
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19
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Jang HJ, Kang B, Choe BH. The difference in extraintestinal manifestations of inflammatory bowel disease for children and adults. Transl Pediatr 2019; 8:4-15. [PMID: 30881893 PMCID: PMC6382501 DOI: 10.21037/tp.2019.01.06] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/22/2018] [Accepted: 01/23/2019] [Indexed: 12/12/2022] Open
Abstract
Extraintestinal manifestations (EIMs) are frequently observed in adult and pediatric patients with inflammatory bowel disease (IBD). The most common EIMs involve the joints, skin, and eyes, but they can affect various organs and result in significant morbidity. Since EIMs can appear years before the diagnosis of IBD is made, clinicians should be aware of their various manifestations to help decrease diagnostic delay of IBD and establish appropriate treatment plans.
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Affiliation(s)
- Hyo-Jeong Jang
- Department of Pediatrics, Keimyung University School of Medicine, Daegu, South Korea
| | - Ben Kang
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, South Korea
| | - Byung-Ho Choe
- Department of Pediatrics, School of Medicine, Kyungpook National University, Daegu, South Korea
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20
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Palmela C, Peerani F, Castaneda D, Torres J, Itzkowitz SH. Inflammatory Bowel Disease and Primary Sclerosing Cholangitis: A Review of the Phenotype and Associated Specific Features. Gut Liver 2018; 12:17-29. [PMID: 28376583 PMCID: PMC5753680 DOI: 10.5009/gnl16510] [Citation(s) in RCA: 103] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/19/2016] [Revised: 12/19/2016] [Accepted: 01/05/2017] [Indexed: 02/06/2023] Open
Abstract
Primary sclerosing cholangitis (PSC) is a chronic, progressive cholestatic disease that is associated with inflammatory bowel disease (IBD) in approximately 70% of cases. Although the pathogenesis is still unknown for both diseases, there is increasing evidence to indicate that they share a common underlying predisposition. Herein, we review the epidemiology, diagnosis, disease pathogenesis, and specific clinical features of the PSC-IBD phenotype. Patients with PSC-IBD have a distinct IBD phenotype with an increased incidence of pancolitis, backwash ileitis, and rectal sparing. Despite often having extensive colonic involvement, these patients present with mild intestinal symptoms or are even asymptomatic, which can delay the diagnosis of IBD. Although the IBD phenotype has been well characterized in PSC patients, the natural history and disease behavior of PSC in PSC-IBD patients is less well defined. There is conflicting evidence regarding the course of IBD in PSC-IBD patients who receive liver transplantation and their risk of recurrent PSC. IBD may also be associated with an increased risk of cholangiocarcinoma in PSC patients. Overall, the PSC-IBD population has an increased risk of developing colorectal neoplasia compared to the conventional IBD population. Lifelong annual surveillance colonoscopy is currently recommended.
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Affiliation(s)
- Carolina Palmela
- Division of Gastroenterology, Surgical Department, Hospital Beatriz Ângelo, Loures, Portugal
| | - Farhad Peerani
- Division of Gastroenterology, Department of Medicine, University of Alberta, Edmonton, AB, Canada
| | - Daniel Castaneda
- Division of Internal Medicine, Mount Sinai St. Luke's and Mount Sinai West Hospitals, New York, NY, USA
| | - Joana Torres
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Steven H Itzkowitz
- Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
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21
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Garg SK, Velayos FS, Kisiel JB. Intestinal and Nonintestinal Cancer Risks for Patients with Crohn's Disease. Gastroenterol Clin North Am 2017; 46:515-529. [PMID: 28838412 DOI: 10.1016/j.gtc.2017.05.006] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
Crohn's disease (CD) is a chronic inflammatory disease that confers a higher risk of cancer than in the general population. New, large, population-based studies in the past decade show that patients with CD are at higher risk of colorectal, small bowel, melanoma, and cervical cancer. Patients who use thiopurines are at additional risk of development of lymphoma and nonmelanoma skin cancer. Preventive surveillance for cancers of the colorectum, skin, and uterine cervix is advised.
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Affiliation(s)
- Sushil K Garg
- Department of Internal Medicine, University of Minnesota, Minneapolis, MN, USA
| | - Fernando S Velayos
- Division of Gastroenterology, University of California San Francisco, San Francisco, CA, USA
| | - John B Kisiel
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street, Southwest, Rochester, MN 55905, USA.
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22
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Pulusu SSR, Lawrance IC. Dysplasia and colorectal cancer surveillance in inflammatory bowel disease. Expert Rev Gastroenterol Hepatol 2017; 11:711-722. [PMID: 28475382 DOI: 10.1080/17474124.2017.1327347] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
Inflammatory bowel disease (IBD) patients are at an increased risk of developing colorectal cancer (CRC), a devastating complication of which intestinal dysplasia is the precursor. Considerable progress has been made to determine CRC risk in IBD, identification & management of dysplasia and preventative methods. Traditionally, surveillance colonoscopies with random colonic biopsies was used. However recent data suggests that chromoendoscopy is a better method of surveillance. Using 5-aminosalicylic acid agents primarily for chemoprevention is an ongoing debate however, when prescribed along with other strategies to control inflammation, their use is considered of benefit. This review presents current understanding of risk factors of neoplasia focusing on dysplasia and preventive strategies. Areas covered: PubMed search was done using key words to assess current evidence. Along with genetics, risk factors, strategies that modify the risk of dysplasia, and CRC in IBD are discussed in detail. Expert commentary: The role of our strategies in modifying CRC risk needs further assessment. Future research should aim to fill knowledge gaps such as high quality evidence for Chromoendoscopy and development of molecular markers for dysplasia detection. Our ultimate goal would be to eliminate CRC and is possible by better understanding of key pathogenic mechanisms in IBD.
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Affiliation(s)
- Samba Siva Reddy Pulusu
- a Centre for Inflammatory Bowel Diseases , Saint John of God Hospital , Subiaco , WA , Australia
| | - Ian C Lawrance
- a Centre for Inflammatory Bowel Diseases , Saint John of God Hospital , Subiaco , WA , Australia.,b Harry Perkins Institute of Medical Research, School of Medicine and Pharmacology , University of Western Australia , Murdoch , WA , Australia
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23
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Komaki Y, Komaki F, Micic D, Ido A, Sakuraba A. Risk of colorectal cancer in chronic liver diseases: a systematic review and meta-analysis. Gastrointest Endosc 2017; 86:93-104.e5. [PMID: 28011280 DOI: 10.1016/j.gie.2016.12.009] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/19/2016] [Accepted: 12/01/2016] [Indexed: 02/07/2023]
Abstract
BACKGROUND AND AIMS The risk of colorectal cancer (CRC) in various chronic liver diseases compared with the general population remains unclear. We performed a systematic review and meta-analysis to assess the risk of CRC in patients with chronic liver diseases before and after liver transplantation. METHODS Electronic databases were searched for studies assessing the risk of CRC in patients with chronic liver diseases. The primary outcome was the pooled risk of CRC among studies that reported the risk as standardized incidence rate (SIR). RESULTS Fifty studies that included 55,991 patients were identified. Among studies that included hepatitis and cirrhotic patients, the pooled SIR was 2.06 (P < .0001; 95% confidence interval (CI), 1.46-2.90) with moderate heterogeneity (I2 = 49.2%), which appeared to be because of the difference between subgroup of diseases and the power of studies. Three studies reported an increased risk of CRC in primary sclerosing cholangitis patients (pooled SIR 6.70; P < .0001; 95% CI, 3.48-12.91) with moderate heterogeneity (I2 = 36.3%), which appeared to be because of the difference between the power of studies. Among studies that included post-transplant patients, the pooled SIR was 2.16 (P < .0001; 95% CI, 1.59-2.94) with moderate heterogeneity (I2 = 56.4%). Meta-regression showed a correlation between the proportion of autoimmune-related liver diseases and the risk of CRC. CONCLUSIONS Patients with chronic liver diseases had an increased risk of CRC compared with the general population, which persisted after liver transplantation. A more intensive surveillance for CRC is warranted in this population.
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Affiliation(s)
- Yuga Komaki
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, Illinois, USA
| | - Fukiko Komaki
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, Illinois, USA
| | - Dejan Micic
- Division of Gastroenterology and Hepatology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Akio Ido
- Digestive and Lifestyle Diseases, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan
| | - Atsushi Sakuraba
- Section of Gastroenterology, Hepatology and Nutrition, Department of Medicine, The University of Chicago Medicine, Chicago, Illinois, USA
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24
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Folic Acid Supplementation May Reduce Colorectal Cancer Risk in Patients With Inflammatory Bowel Disease: A Systematic Review and Meta-Analysis. J Clin Gastroenterol 2017; 51:247-253. [PMID: 26905603 DOI: 10.1097/mcg.0000000000000498] [Citation(s) in RCA: 53] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
GOALS To evaluate the role of folic acid supplementation in colorectal cancer (CRC) chemoprevention in patients with inflammatory bowel disease (IBD). BACKGROUND CRC is a serious complication of IBD. Folic acid supplementation has been shown to be chemopreventative in sporadic CRC. Patients with IBD are at risk of folate deficiency though intestinal malabsorption and also competitive inhibition by concurrent sulfasalazine use. To date, there have been several studies reporting on folic acid supplementation in patients with IBD and CRC. STUDY We searched electronic databases for studies reporting folic acid use and CRC incidence in patients with IBD. We produced a pooled hazard ratio with 95% confidence intervals using a random-effects model. Preplanned subgroup analyses were performed to explore for any potential sources of heterogeneity. RESULTS Ten studies reporting on 4517 patients were included. We found an overall protective effect for folic acid supplementation on the development of CRC, pooled hazard ratio=0.58 (95% confidence interval, 0.37-0.80). There was low to moderate heterogeneity among studies, I=29.7%. Subgroup analyses suggested that folic acid use was protective in hospital-based studies, studies from North America and those that were performed before folate fortification of foods in 1998. CONCLUSIONS CRC remains an important complication of IBD. Chemoprevention is an attractive strategy and folic acid as a cheap, safe, and well-tolerated supplement may have a role. Focused prospective studies are required to precisely define any potential effect.
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Toh JWT, Stewart P, Rickard MJFX, Leong R, Wang N, Young CJ. Indications and surgical options for small bowel, large bowel and perianal Crohn's disease. World J Gastroenterol 2016; 22:8892-8904. [PMID: 27833380 PMCID: PMC5083794 DOI: 10.3748/wjg.v22.i40.8892] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/14/2016] [Revised: 08/26/2016] [Accepted: 09/28/2016] [Indexed: 02/06/2023] Open
Abstract
Despite advancements in medical therapy of Crohn's disease (CD), majority of patients with CD will eventually require surgical intervention, with at least a third of patients requiring multiple surgeries. It is important to understand the role and timing of surgery, with the goals of therapy to reduce the need for surgery without increasing the odds of emergency surgery and its associated morbidity, as well as to limit surgical recurrence and avoid intestinal failure. The profile of CD patients requiring surgical intervention has changed over the decades with improvements in medical therapy with immunomodulators and biological agents. The most common indication for surgery is obstruction from stricturing disease, followed by abscesses and fistulae. The risk of gastrointestinal bleeding in CD is high but the likelihood of needing surgery for bleeding is low. Most major gastrointestinal bleeding episodes resolve spontaneously, albeit the risk of re-bleeding is high. The risk of colorectal cancer associated with CD is low. While current surgical guidelines recommend a total proctocolectomy for colorectal cancer associated with CD, subtotal colectomy or segmental colectomy with endoscopic surveillance may be a reasonable option. Approximately 20%-40% of CD patients will need perianal surgery during their lifetime. This review assesses the practice parameters and guidelines in the surgical management of CD, with a focus on the indications for surgery in CD (and when not to operate), and a critical evaluation of the timing and surgical options available to improve outcomes and reduce recurrence rates.
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Pellino G, Marcellinaro R, Sciaudone G, Reginelli A, Esposito P, Riegler G, Canonico S, Villanacci V, Selvaggi F. Large bowel cancer in the setting of inflammatory bowel disease. Eur Surg 2016; 48:191-202. [DOI: 10.1007/s10353-016-0434-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
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Burr NE, Hull MA, Subramanian V. Does aspirin or non-aspirin non-steroidal anti-inflammatory drug use prevent colorectal cancer in inflammatory bowel disease? World J Gastroenterol 2016; 22:3679-3686. [PMID: 27053860 PMCID: PMC4814654 DOI: 10.3748/wjg.v22.i13.3679] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/29/2015] [Revised: 02/09/2016] [Accepted: 03/02/2016] [Indexed: 02/06/2023] Open
Abstract
AIM: To determine whether aspirin or non-aspirin non-steroidal anti-inflammatory drugs (NA-NSAIDs) prevent colorectal cancer (CRC) in patients with inflammatory bowel disease (IBD).
METHODS: We performed a systematic review and meta-analysis. We searched for articles reporting the risk of CRC in patients with IBD related to aspirin or NA-NSAID use. Pooled odds ratios (OR) and 95%CIs were determined using a random-effects model. Publication bias was assessed using Funnel plots and Egger’s test. Heterogeneity was assessed using Cochran’s Q and the I2 statistic.
RESULTS: Eight studies involving 14917 patients and 3 studies involving 1282 patients provided data on the risk of CRC in patients with IBD taking NA-NSAIDs and aspirin respectively. The pooled OR of developing CRC after exposure to NA-NSAIDs in patients with IBD was 0.80 (95%CI: 0.39-1.21) and after exposure to aspirin it was 0.66 (95%CI: 0.06-1.39). There was significant heterogeneity (I2 > 50%) between the studies. There was no change in the effect estimates on subgroup analyses of the population studied or whether adjustment or matching was performed.
CONCLUSION: There is a lack of high quality evidence on this important clinical topic. From the available evidence NA-NSAID or aspirin use does not appear to be chemopreventative for CRC in patients with IBD.
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Zheng HH, Jiang XL. Increased risk of colorectal neoplasia in patients with primary sclerosing cholangitis and inflammatory bowel disease: a meta-analysis of 16 observational studies. Eur J Gastroenterol Hepatol 2016; 28:383-390. [PMID: 26938805 DOI: 10.1097/meg.0000000000000576] [Citation(s) in RCA: 99] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis (UC) patients with concomitant primary sclerosing cholangitis (PSC) carry an increased risk of colorectal neoplasia (dysplasia and cancer), whereas the association between PSC and the development of colorectal neoplasia in Crohn's disease (CD) is controversial. A meta-analysis was carried out to compare the risk of this neoplasia in patients with inflammatory bowel disease (IBD) with and without PSC. A systematic research of MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials was performed to identify studies that compared the risk of colorectal neoplasia (dysplasia and cancer) in patients with IBD with and without PSC. Quality assessment was performed using the Newcastle-Ottawa Scale. Pooled odds ratio (OR) was calculated using the random-effects model by STATA 12.0. A total of 16 studies (four cohort studies, 12 case-control studies; nine prospective studies and seven retrospective studies) were selected for further study. These studies included 13 379 IBD patients, of whom 1022 also had PSC. Patients with IBD and PSC were at an increased risk of colorectal dysplasia and cancer compared with patients with IBD alone [OR 3.24; 95% confidence interval (CI): 2.14-4.90]. This increased risk was present even when the risk of colorectal cancer alone was analysed (OR 3.41; 95% CI: 2.13-5.48). Data only from patients with UC showed that PSC was associated with an increased risk for the development of colorectal neoplasia and cancer in patients with UC (OR 2.98; 95% CI: 1.54-5.76) (OR 3.01; 95% CI: 1.44-6.29), but there were high heterogeneity among studies (I=76.9 and 62.8%, respectively). Heterogeneity of the studies was affected by the study design (prospective or retrospective). The OR of colorectal neoplasia was 2.32 (95% CI: 0.70-7.70, P=0.133) and that of cancer was 2.91 (95% CI: 0.84-10.16, P=0.388) for patients with CD and concurrent PSC. Patients with IBD and PSC have a markedly higher risk for the development of colorectal neoplasia than patients with IBD, but not PSC. Stratification by IBD type show that the presence of PSC is associated with an increased risk for the development of colorectal neoplasia in patients with UC; however, there is a nonsignificant association in CD patients. When the risk of colorectal cancer alone is analysed, the conclusion does not change.
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Affiliation(s)
- Han-Han Zheng
- aPostgraduate Training Base of the General Hospital of Jinan Military Command, Liaoning Medical UniversitybDepartment of Gastroenterology, The General Hospital of Jinan Military Command, Jinan, Shandong, China
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Ou B, Zhao J, Guan S, Lu A. Survival of Colorectal Cancer in Patients With or Without Inflammatory Bowel Disease: A Meta-Analysis. Dig Dis Sci 2016; 61:881-9. [PMID: 26518415 DOI: 10.1007/s10620-015-3940-1] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/13/2015] [Accepted: 10/22/2015] [Indexed: 12/14/2022]
Abstract
BACKGROUND Patients with inflammatory bowel disease (IBD) are at increased risk of colorectal cancer (CRC), but little is known about the influence of IBD on CRC prognosis. AIMS The aim of this study was to perform a meta-analysis to compare survival in CRC patients with IBD (IBD-CRC) and without IBD. METHODS An electronic search was conducted via PubMed, Embase, and the Cochrane Library to identify eligible trials until July 2015. We pooled the hazard ratios (HRs) and their 95% confidence intervals (CIs) to quantitatively assess the survival of CRC in patients with or without IBD. In addition, clinicopathological parameters of IBD-CRC versus non-IBD CRC were evaluated. RESULTS Twelve studies containing a total of 3472 IBD-CRC patients were eligible according to our selection criteria. Our analysis indicated that CRC patients with IBD had shorter overall survival than those without IBD (HR 1.24, 95% CI 1.19-1.29). IBD-CRC showed a propensity to develop in proximal colon [odds ratio (OR) 2.52, 95% CI 1.35-4.72] and correlated with worse differentiation of tumor (OR 1.59, 95% CI 1.26-1.99) compared to non-IBD CRC. Meta-regression analysis showed that sample size (P = 0.002) could explain 99.01% inter-study heterogeneity. CONCLUSION This meta-analysis found poorer overall survival in CRC patients with IBD than CRC patients without IBD, and further prospective research to confirm these findings is warranted.
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Affiliation(s)
- Baochi Ou
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Jingkun Zhao
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Shaopei Guan
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China
| | - Aiguo Lu
- Shanghai Minimally Invasive Surgery Center, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, 197 Ruijin Er Road, Shanghai, 200025, China.
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Colorectal Cancer in Patients With Inflammatory Bowel Disease: The Need for a Real Surveillance Program. Clin Colorectal Cancer 2016; 15:204-12. [PMID: 27083409 DOI: 10.1016/j.clcc.2016.02.002] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/08/2015] [Revised: 12/31/2015] [Accepted: 02/03/2016] [Indexed: 02/06/2023]
Abstract
The association between inflammatory bowel disease (IBD) and colorectal cancer (CRC) has been widely shown. This association is responsible for 10% to 15% of deaths in patients with IBD, even if according to some studies, the risk of developing CRC seems to be decreased. An adequate surveillance of patients identified as at-risk patients, might improve the management of IBD-CRC risk. In this article we review the literature data related to IBD-CRC, analyze potential risk factors such as severity of inflammation, duration, and extent of IBD, age at diagnosis, sex, family history of sporadic CRC, and coexistent primary sclerosing cholangitis, and update epidemiology on the basis of new studies. Confirmed risk factors for IBD-CRC are severity, extent, and duration of colitis, the presence of coexistent primary sclerosing cholangitis, and a family history of CRC. Current evidence-based guidelines recommend surveillance colonoscopy for patients with colitis 8 to 10 years after diagnosis, further surveillance is decided on the basis of patient risk factors. The classic white light endoscopy, with random biopsies, is now considered unsatisfactory. The evolution of technology has led to the development of new techniques that promise to increase the effectiveness of the monitoring programs. Chromoendoscopy has already proved highly effective and several guidelines suggest its use with a target biopsy. Confocal endomicroscopy and autofluorescence imaging are currently being tested and for this reason they have not yet been considered as useful in surveillance programs.
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic, progressive disease characterized by inflammatory and fibrosing strictures of the biliary tree. PSC is associated with a high lifetime risk of hepatobiliary and colorectal cancers. The nature of the carcinogenic process in PSC is not well established. The lack of diagnostic methods for early detection and the limited therapeutic options for cholangiocarcinoma constitute a major challenge in the current handling of PSC patients. The article reviews the risk for cancer development in PSC and discusses surveillance strategies for PSC-associated cancers.
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Affiliation(s)
- Trine Folseraas
- Section of Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Rikshospitalet, Oslo, Norway
| | - Kirsten Muri Boberg
- Section of Gastroenterology, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway; Institute of Clinical Medicine, University of Oslo, Rikshospitalet, Oslo, Norway.
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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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Yoon J, Oh SH, Kim HJ, Park SH, Ye BD, Yang SK, Kim KM. Primary Sclerosing Cholangitis with Inflammatory Bowel Disease in Korean Children. Pediatr Gastroenterol Hepatol Nutr 2015; 18:268-75. [PMID: 26770902 PMCID: PMC4712540 DOI: 10.5223/pghn.2015.18.4.268] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/08/2015] [Revised: 10/27/2015] [Accepted: 11/14/2015] [Indexed: 12/13/2022] Open
Abstract
PURPOSE Primary sclerosing cholangitis (PSC) is a rare condition that can be associated with inflammatory bowel disease (IBD). The aim of this study was to evaluate PSC and its association with IBD in children. METHODS We retrospectively enrolled 13 pediatric patients (<18 years) with PSC treated at Asan Medical Center between June 1989 and December 2013. Clinical findings and long-term outcomes were investigated. During the same period, the incidence of PSC among IBD patients was evaluated among 600 Crohn disease (CD) and 210 ulcerative colitis (UC) patients. RESULTS All 13 study patients diagnosed with PSC also presented with IBD. Eleven boys and two girls with a median age of 15.0 years old (9.0-17.8 years) were included. The cumulative incidence of PSC for UC was 5.7% (12 of 210) and 0.2% for CD (1 of 600), respectively. PSC occurred during follow-up for IBD for five patients (38.5%) whereas, IBD developed during follow-up for PSC for two patients (15.4%), and was diagnosed during the initial work-up for PSC for 6 patients (46.2%). For the 77.3 month median follow-up period, 9/13 patients (69.2%), neither the clinical symptoms nor blood test results worsened. Two cases (15.4%) developed liver cirrhosis and underwent liver transplantation. Among 13 PSC patients with IBD, two (15.4%) developed colorectal cancer, and no one developed cholangiocarcinoma. CONCLUSION All patients with PSC in this study had associated IBD. The incidence of PSC was not rare compared to reports in adults. PSC should be considered during the management of IBD and vice versa in children.
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Affiliation(s)
- Jisun Yoon
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Seak Hee Oh
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Hyun Jin Kim
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Sang Hyoung Park
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
| | - Byong Duk Ye
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Suk-Kyun Yang
- Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
| | - Kyung Mo Kim
- Department of Pediatrics, Asan Medical Center Children's Hospital, University of Ulsan College of Medicine, Seoul, Korea
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Abstract
INTRODUCTION Primary sclerosing cholangitis (PSC) is a progressive cholestatic disorder that ultimately can lead to cirrhosis, liver failure, malignancy and death. It is strongly associated with inflammatory bowel disease (IBD), and though a rare disease, its incidence is increasing. There are no proven medical therapies for PSC. SOURCES OF DATA Ovid Medline was utilised to search for articles with keywords 'sclerosing cholangitis' and 'cholangiocarcinoma' and containing titles 'primary sclerosing cholangitis', and references of these papers were cross-referenced for further relevant manuscripts. AREAS OF AGREEMENT PSC is a rare disease, and there is a strong association with risk loci within the major histocompatibility complex and other genes common to other autoimmune diseases. PSC is a premalignant condition, associated with higher rates of hepatobiliary and colorectal cancer in patients with ulcerative colitis (UC). AREAS OF CONTROVERSY The pathogenesis is unclear, and competing theories exist surrounding toxic bile acids, enhanced homing of particular T cells from the gut to the liver and increased passage of toxins to the liver through a permeable bowel wall. It is unclear whether the higher rate of colonic cancer in PSC/UC occurs in PSC/Crohn's disease. Ursodeoxycholic acid therapy reduces liver enzymes but has not been shown to improve survival. It may reduce the prevalence of bowel cancer. GROWING POINTS Recent genetic studies have revealed new risk loci, pointing to the importance of the immune system and its interaction with the biome. AREAS TIMELY FOR DEVELOPING RESEARCH On the basis of the genetic studies discussed earlier, novel agents are being developed and trialled in the treatment of PSC.
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Affiliation(s)
- Kate D Williamson
- Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
| | - Roger W Chapman
- Nuffield Department of Clinical Medicine, University of Oxford, Oxford, UK Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
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Navaneethan U, Rai T, Venkatesh PG, Kiran RP. Primary sclerosing cholangitis and the risk of colon neoplasia in patients with Crohn's colitis. Gastroenterol Rep (Oxf) 2015; 4:226-31. [PMID: 25725040 PMCID: PMC4976675 DOI: 10.1093/gastro/gov007] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/18/2014] [Accepted: 01/06/2015] [Indexed: 01/20/2023] Open
Abstract
Background and aim: Crohn’s colitis (CC) is associated with primary sclerosing cholangitis (PSC). However the risk of colon cancer or dysplasia in CC and PSC is unclear. Our aim was to study the risk of colon neoplasia in CC in patients with and without PSC. Methods: This is a nested, case-control cohort study of all patients diagnosed with concurrent CC and PSC, seen at the Cleveland Clinic between 1985 and 2012. Forty-three patients with both CC and PSC were compared with a random sample of 159 CC controls without PSC during the same period. Results: Seven (16.3%) of 43 CC patients with PSC developed colon cancer or dysplasia, compared with 22 (13.8%) of 159 controls (P = 0.98). Of seven colon neoplasia cases in the PSC group, 100% occurred proximal to the splenic flexure, compared with 50% (11/22) cases of colon neoplasia in controls occurring in the proximal colon (P = 0.001). Based on Cox regression analysis, male gender independently increased the risk of neoplasia [hazard ratio (HR) = 2.68; 95% confidence interval (CI) 1.30–5.54; P = 0.008], as did age at CC diagnosis (HR = 1.29; 95% CI 1.14–1.47; P < 0.001), while the use of azathioprine/6-mercaptopurine was protective (HR = 0.30; 95% CI 0.13–0.70; P = 0.005). The presence of PSC did not increase the risk for colon neoplasia (HR = 0.45; 95% CI 0.18–1.13; P = 0.09). Conclusions: CC patients with PSC appear not to be at increased risk of developing colon neoplasia. Among patients in our cohort with colon neoplasia and concurrent PSC, the neoplasia occurred in the proximal colon in all cases.
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Affiliation(s)
- Udayakumar Navaneethan
- Department of Gastroenterology, Digestive disease Institute, The Cleveland Clinic, Cleveland, OH, USA
| | - Tarun Rai
- Department of Gastroenterology, Digestive disease Institute, The Cleveland Clinic, Cleveland, OH, USA
| | - Preethi Gk Venkatesh
- Department of Gastroenterology, Digestive disease Institute, The Cleveland Clinic, Cleveland, OH, USA
| | - Ravi P Kiran
- Department of Colorectal Surgery, Digestive disease Institute, The Cleveland Clinic, Cleveland, OH, USA
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de Vries AB, Janse M, Blokzijl H, Weersma RK. Distinctive inflammatory bowel disease phenotype in primary sclerosing cholangitis. World J Gastroenterol 2015; 21:1956-1971. [PMID: 25684965 PMCID: PMC4323476 DOI: 10.3748/wjg.v21.i6.1956] [Citation(s) in RCA: 138] [Impact Index Per Article: 13.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2014] [Revised: 10/31/2014] [Accepted: 01/08/2015] [Indexed: 02/06/2023] Open
Abstract
AIM: To review the current literature for the specific clinical characteristics of inflammatory bowel disease (IBD) associated with primary sclerosing cholangitis (PSC).
METHODS: A systematical review for clinical characteristics of IBD in PSC was performed by conducting a broad search for “primary sclerosing cholangitis” in Pubmed. “Clinical characteristics” were specified into five predefined subthemes: epidemiology of IBD in PSC, characteristics of IBD in PSC (i.e., location, disease behavior), risk of colorectal cancer development, IBD recurrence and de novo disease after liver transplantation for PSC, and safety and complications after proctocolectomy with ileal pouch-anal anastomosis. Papers were selected for inclusion based on their relevance to the subthemes, and were reviewed by two independent reviewers. Only full papers relevant to PSC-IBD were included. Additionally the references of recent reviews for PSC (< 5 years old) were scrutinized for relevant articles.
RESULTS: Initial literature search for PSC yielded 4704 results. After careful review 65 papers, comprising a total of 11406 PSC-IBD patients, were selected and divided according to subtheme. Four manuscripts overlapped and were included in two subthemes. Prevalence of IBD in PSC shows a large variance, ranging from 46.5% to 98.7% with ulcerative colitis (UC) being the most common type (> 75%). The highest IBD rates in PSC are found in papers reviewing both endoscopic and histological data for IBD diagnosis. Although IBD in PSC is found to be a quiescent disease, pancolitis occurs often, with rates varying from 35% to 95%. Both backwash ileitis and rectal sparing are observed infrequently. The development of dysplasia or colorectal carcinoma is increased in PSC-IBD; the cumulative 10 years risk varying between 0% and 11%. Exacerbation of IBD is common after liver transplantation for PSC and de novo disease is seen in 1.3% to 31.3% of PSC-IBD patients. The risk for development of pouchitis in PSC-IBD is found to be significant, affecting 13.8% to 90% of the patients after proctocolectomy with ileo anal-pouch anastomosis.
CONCLUSION: IBD in primary sclerosing cholangitis represents a distinct phenotype that differs from UC and Crohn’s disease and therefore requires specialized management.
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Navaneethan U, Venkatesh PG, Jegadeesan R, Lourdusamy V, Hammel JP, Kiran RP, Shen B. Comparison of outcomes for patients with primary sclerosing cholangitis associated with ulcerative colitis and Crohn's disease. Gastroenterol Rep (Oxf) 2014; 4:43-9. [PMID: 25355801 PMCID: PMC4760060 DOI: 10.1093/gastro/gou074] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2014] [Accepted: 09/23/2014] [Indexed: 12/26/2022] Open
Abstract
Background: The comparative outcomes of ulcerative colitis (UC) and Crohn’s disease (CD) in patients with primary sclerosing cholangitis (PSC) are unclear; the aim of our study was to make an objective comparison. Methods: A total of 273 patients with PSC and inflammatory bowel disease (223 with UC and 50 with CD) were included. Clinical and demographic variables were obtained. Results: The PSC risk score was similar for both groups. The median follow-up period in patients with PSC-UC was 12 years (range 0–38) and that for PSC-CD was 14 years (range 1–36). The median number of disease flares per year was higher in PSC-UC patients than in the PSC-CD group [1vs.0 (ranges 0–20 and 0–9, respectively); P < 0.001]. More patients with UC developed colon neoplasia than CD (35.9% vs.18%; P = 0.009). On proportional hazards analysis for the risk of colectomy, UC patients had a 12% higher risk for colectomy [hazard ratio (HR) = 0.88; 95% confidence interval (CI) 0.51–1.51; P = 0.64]. Liver transplantation for PSC was associated with decreased risk (HR = 0.57; 95% CI 0.37–0.89; P = 0.013), while colon neoplasia increased the risk (HR = 3.83; 95% CI 2.63–5.58; P < 0.001) for colectomy. On proportional hazards analysis for the risk of colon neoplasia, UC patients had 56% higher risk of developing colon neoplasia than CD (HR = 0.44; 95% CI 0.16–1.25; P = 0.12). Conclusions: PSC patients with CD appear to be associated with a lower risk of colon neoplasia and colectomy than PSC patients with UC.
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Affiliation(s)
- Udayakumar Navaneethan
- Department of Gastroenterology, Digestive Disease Institute, The Cleveland Clinic, Cleveland, OH, USA
| | - Preethi Gk Venkatesh
- Department of Gastroenterology, Digestive Disease Institute, The Cleveland Clinic, Cleveland, OH, USA
| | - Ramprasad Jegadeesan
- Department of Gastroenterology, Digestive Disease Institute, The Cleveland Clinic, Cleveland, OH, USA
| | - Vennisvasanth Lourdusamy
- Department of Gastroenterology, Digestive Disease Institute, The Cleveland Clinic, Cleveland, OH, USA
| | - Jeffrey P Hammel
- Department of Gastroenterology, Digestive Disease Institute, The Cleveland Clinic, Cleveland, OH, USA
| | - Ravi P Kiran
- Department of Colorectal Surgery, Columbia University Medical Center, New York Presbyterian Hospital, New York, NY, USA
| | - Bo Shen
- Department of Gastroenterology, Digestive Disease Institute, The Cleveland Clinic, Cleveland, OH, USA
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38
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Wang R, Leong RM. Primary sclerosing cholangitis as an independent risk factor for colorectal cancer in the context of inflammatory bowel disease: A review of the literature. World J Gastroenterol 2014; 20:8783-8789. [PMID: 25083052 PMCID: PMC4112886 DOI: 10.3748/wjg.v20.i27.8783] [Citation(s) in RCA: 34] [Impact Index Per Article: 3.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/13/2013] [Revised: 01/21/2014] [Accepted: 04/09/2014] [Indexed: 02/06/2023] Open
Abstract
To examine and evaluate recent evidence regarding the epidemiology, pathogenesis and management of colorectal cancer (CRC) development in inflammatory bowel disease (IBD)-primary sclerosing cholangitis (PSC) patients. Using the PubMed database, a literature search was conducted for relevant articles in English from the past 10 years. Relevant studies investigating PSC as a risk factor for CRC in IBD in the context of incidence and prevalence, pathogenesis, prevention and prognosis were included in this review. Recent evidence increasingly points to PSC as a significant risk factor in the development of CRC in patients with concomitant IBD. PSC may be an important risk factor for CRC in different populations worldwide. The mechanism for this increase in risk is still unclear. The efficacy of UDCA as a chemopreventive agent remains controversial. Liver transplantation does not halt the development of CRC, although there is not enough evidence to suggest that it is associated with increased incidence of CRC. While routine colonoscopic surveillance should be performed in patients with concurrent PSC and IBD, more high-level evidence is required to support the benefits of the procedure. While many new developments have taken place in the last decade, the pathogenesis and optimal management of CRC development in IBD-PSC patients remain unclear.
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic, cholestatic liver disease caused by diffuse inflammation and fibrosis that can involve the entire biliary tree. It is a progressive disorder which can ultimately lead to biliary cirrhosis, portal hypertension and hepatic failure. PSC is a complex genetic disorder with male predominance. Environmental predisposing factors include non-smoking. It is closely associated with inflammatory bowel disease (IBD), particularly ulcerative colitis, which occurs in about two thirds of PSC cases. Recent studies have suggested that PSC-IBD is a separate disease entity from IBD alone with distinctive genetic and phenotypic characteristics. Most PSC patients are asymptomatic at presentation; clinical symptoms include fatigue, jaundice, weight loss, right upper quadrant pain and pruritis. Serum biochemical tests indicate cholestasis, and diagnosis is usually established by cholangiography. In symptomatic patients, median survival from presentation to death or liver transplantation is about 12 years. It is a premalignant condition, and the majority of deaths are from malignancy, particularly cholangiocarcinoma or colonic cancer. PSC has no curative treatment. Medical treatment with ursodeoxycholic acid may slow progression of the disease and reduce colonic dysplasia, though trials lack statistical significance. Liver transplantation is the only option in young patients with PSC and advanced liver disease.
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Sebastian S, Hernández V, Myrelid P, Kariv R, Tsianos E, Toruner M, Marti-Gallostra M, Spinelli A, van der Meulen-de Jong AE, Yuksel ES, Gasche C, Ardizzone S, Danese S. Colorectal cancer in inflammatory bowel disease: results of the 3rd ECCO pathogenesis scientific workshop (I). J Crohns Colitis 2014; 8:5-18. [PMID: 23664897 DOI: 10.1016/j.crohns.2013.04.008] [Citation(s) in RCA: 94] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/23/2013] [Accepted: 04/05/2013] [Indexed: 02/08/2023]
Abstract
Epidemiological studies demonstrate an increased risk of colorectal cancer in patients with inflammatory bowel disease (IBD). A detailed literature review was conducted on epidemiology, risk factors, pathophysiology, chemoprevention and outcomes of colorectal cancer (CRC) in IBD as part of the 3rd ECCO scientific pathogenesis workshop.
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Affiliation(s)
- Shaji Sebastian
- Hull & East Yorkshire Hospitals NHS Trust, Hull York Medical School, Hull, United Kingdom.
| | - Vincent Hernández
- Gastroenterology Department, Complexo Hospitalario Universitario de Vigo, Vigo, Spain
| | - Pär Myrelid
- Division of Surgery, Department of Clinical and Experimental Medicine, Faculty of Health Sciences, Linköping University, County Council of Östergötland, Linköping, Sweden
| | - Revital Kariv
- Service for Gastrointestinal Malignancies, Department of Gastroenterology & Liver Disease, Tel Aviv Sourasky Medical Center, Israel
| | - Epameinondas Tsianos
- University of Ioannina, 1st Division of Internal Medicine and Hepato-Gastroenterology Unit, Greece
| | - Murat Toruner
- Ankara University Medical School, Ibni Sina Hospital, Division of Gastroenterology, Ankara, Turkey
| | - Marc Marti-Gallostra
- Department of Colorectal Surgery, University Hospital of Valle de Hebron, Barcelona, Spain
| | - Antonino Spinelli
- Dipartimento e Cattedra di Chirurgia Generale, Istituto Clinico Humanitas IRCCS, Università degli Studi di Milano, Rozzano, Milano, Italy
| | | | - Elif Sarıtas Yuksel
- Department of Gastroenterology, Katip Celebi University, Ataturk Research and Teaching Hospital, Izmir, Turkey
| | - Christoph Gasche
- Christian Doppler Laboratory on Molecular Cancer Chemoprevention, Division of Gastroenterology, Medical University of Vienna, Vienna, Austria
| | - Sandro Ardizzone
- Chair of Gastroenterology, "L. Sacco" University Hospital, Milan, Italy
| | - Silvio Danese
- Department of Gastroenterology, Istituto Clinico Humanitas, Milan, Italy.
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Hrabe JE, Byrn JC, Button AM, Zamba GK, Kapadia MR, Mezhir JJ. A matched case-control study of IBD-associated colorectal cancer: IBD portends worse outcome. J Surg Oncol 2013; 109:117-21. [PMID: 24132737 DOI: 10.1002/jso.23465] [Citation(s) in RCA: 22] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2013] [Accepted: 09/17/2013] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND OBJECTIVES The effect of inflammatory bowel disease (IBD) on outcome in patients with colorectal cancer (CRC) remains unclear. Our objective is to evaluate oncologic outcomes of patients with IBD-associated CRC. METHODS We retrospectively reviewed a prospectively maintained database to identify patients with IBD-associated CRC. Clinicopathologic variables and overall survival were compared to patients with sporadic CRC using a 2:1 matched-controlled analysis. RESULTS Fifty-five patients with IBD and CRC were identified. On univariate analysis, CRC patients with IBD had a significantly shorter median overall survival (68.2 months vs. 204.3 months, P = 0.01) compared to patients with sporadic CRC. On multivariate analysis, after adjusting for N and M stage, IBD was associated with an increased risk of death compared to sporadic CRC (HR = 2.011, 95% CI 1.24-3.23, P = 0.004). Stage 3 CRC patients with IBD in particular showed significantly decreased survival (23.0 vs. 133.9 months, P = 0.008). CONCLUSIONS In this study, patients with node-positive IBD-associated CRC had a significant increased risk of death and a shorter overall survival than those with sporadic disease and may require tailored adjuvant therapy and surveillance protocols. Continued investigation to elucidate the mechanisms that contribute to these observations is justified.
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Affiliation(s)
- Jennifer E Hrabe
- Department of Surgery, The University of Iowa Hospitals and Clinics, Iowa City, Iowa
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Eaton JE, Talwalkar JA, Lazaridis KN, Gores GJ, Lindor KD. Pathogenesis of primary sclerosing cholangitis and advances in diagnosis and management. Gastroenterology 2013; 145:521-36. [PMID: 23827861 PMCID: PMC3815445 DOI: 10.1053/j.gastro.2013.06.052] [Citation(s) in RCA: 282] [Impact Index Per Article: 23.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/07/2013] [Revised: 05/18/2013] [Accepted: 06/24/2013] [Indexed: 02/08/2023]
Abstract
Primary sclerosing cholangitis (PSC), first described in the mid-1850s, is a complex liver disease that is heterogeneous in its presentation. PSC is characterized by chronic cholestasis associated with chronic inflammation of the biliary epithelium, resulting in multifocal bile duct strictures that can affect the entire biliary tree. Chronic inflammation leads to fibrosis involving the hepatic parenchyma and biliary tree, which can lead to cirrhosis and malignancy. The etiology of PSC is not fully understood, which in part explains the lack of effective medical therapy for this condition. However, we have begun to better understand the molecular pathogenesis of PSC. The recognition of specific clinical subtypes and their pattern of progression could improve phenotypic and genotypic classification of the disease. We review our current understanding of this enigmatic disorder and discuss important topics for future studies.
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Affiliation(s)
- John E. Eaton
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN
| | - Jayant A. Talwalkar
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN,Corresponding Author: Jayant A. Talwalkar, M.D., M.P.H., Professor of Medicine, Division of Gastroenterology & Hepatology, Mayo Clinic, 200 First Street S.W., Rochester, MN 55905, Secretary: 507-284-4823, Fax: 507-284-0538,
| | | | - Gregory J. Gores
- Division of Gastroenterology & Hepatology, Mayo Clinic, Rochester, MN
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43
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Karlsen TH, Boberg KM. Update on primary sclerosing cholangitis. J Hepatol 2013; 59:571-82. [PMID: 23603668 DOI: 10.1016/j.jhep.2013.03.015] [Citation(s) in RCA: 85] [Impact Index Per Article: 7.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2013] [Revised: 03/12/2013] [Accepted: 03/14/2013] [Indexed: 12/16/2022]
Abstract
Primary sclerosing cholangitis (PSC) remains one of the most challenging conditions of clinical hepatology. There has been a steady growth in research to overcome this fact and the present review aims at summarizing the most recently published literature. The main emphasis will be put on the link of recent pathogenetic insights to clinical characteristics and patient management. With regard to pathogenesis, there is no consensus yet as to whether immune mediated injury or factors related to bile acid physiology are the most important. It also remains to be clarified whether PSC is a mixed bag of various secondary etiologies yet to be defined, or a disease entity predominantly represented by sclerosing cholangitis in the context of inflammatory bowel disease. Most important, there is no available medical therapy with proven influence on clinical end points, and timing of liver transplantation and patient follow-up are challenging due to the unpredictable and high risk of cholangiocarcinoma.
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Affiliation(s)
- Tom H Karlsen
- Norwegian PSC Research Center, Department of Transplantation Medicine, Division of Cancer Medicine, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway
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44
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Koudougou C, Bonneville M, Matysiak-Budnik T, Touchefeu Y. Review article: antitumoural immunity in colorectal cancer - current and potential future implications in clinical practice. Aliment Pharmacol Ther 2013; 38:3-15. [PMID: 23692025 DOI: 10.1111/apt.12337] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/01/2013] [Revised: 02/21/2013] [Accepted: 04/29/2013] [Indexed: 12/22/2022]
Abstract
BACKGROUND Most of the current research in gastrointestinal oncology is focused on biology of cancer itself, but there is growing interest in the patient's immune system response and its relation with cancer cells. AIM To review the impact of the antitumoural immune response on epidemiology, prognosis and treatment of colorectal cancer. METHODS Search of the literature published in English using the PubMed database. RESULTS The role of the immune system in the antitumoural immunosurveillance is clearly supported by the increased incidence of colorectal cancer and adenomatous polyps in immunosuppressed patients. Moreover, the degree of infiltration of the tumours by the immune cells has been shown to be a strong prognostic factor of both disease recurrence and survival. The immune system plays an important role in the chemotherapy-induced cell death. New therapeutic strategies targeting the antitumoural immunity are being currently investigated with promising results. CONCLUSION Better knowledge of antitumoural immune system can have a major impact on patients' management in daily clinical practice. Colorectal cancer screening is an important issue in immunosuppressed patients, and recommendations should be refined for selected high-risk patients. The use of an immune score to guide the therapeutic strategies in the adjuvant setting should be supported. Further and larger clinical trials are necessary to accelerate the development of innovative immune therapies.
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Affiliation(s)
- C Koudougou
- Institut des Maladies de l'Appareil Digestif & Digestive Oncology Unit, CHU de Nantes, Nantes Cedex, France
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45
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic, progressive, cholestatic liver disease characterized by multifocal strictures of intra and extrahepatic bile ducts. PSC occurs more commonly in men and is often associated with inflammatory bowel disease. At present, there is no effective medical therapy for PSC. Current management of patients with PSC is centered on endoscopic therapy of biliary strictures, management of complications of chronic cholestasis and of progressive liver disease, and close clinical monitoring for development of cholangiocarcinoma, as well as for timely referral for liver transplantation.
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Affiliation(s)
- Claudia O Zein
- Department of Gastroenterology and Hepatology, Digestive Disease Institute, Cleveland Clinic, 9500 Euclid Avenue, A31, Cleveland, OH 44195, USA.
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Kekilli M, Tunc B, Beyazit Y, Kurt M, Onal IK, Ulker A, Haznedaroglu IC. Circulating CD4+CD25+ regulatory T cells in the pathobiology of ulcerative colitis and concurrent primary sclerosing cholangitis. Dig Dis Sci 2013; 58:1250-1255. [PMID: 23306841 PMCID: PMC3661043 DOI: 10.1007/s10620-012-2511-y] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/20/2012] [Accepted: 12/01/2012] [Indexed: 12/13/2022]
Abstract
BACKGROUND Immunopathogenetic features of primary sclerosing cholangitis (PSC) in ulcerative colitis (UC) still remains unclear. Peripheral blood CD4+CD25+ regulatory T cells have a key role in the induction and maintenance of peripheral self-tolerance and inhibit several organ-specific autoimmune diseases. Therefore, CD4+CD25+ T cells are believed to play an essential role in autoimmune diseases. The aim of the present study is to analyze the role of CD4+CD25+ T cells in the pathogenesis of UC-associated PSC. METHODS This study evaluated the levels of CD4+CD25+ T cells in peripheral blood mononuclear cells (PBMC) of 27 UC patients with PSC and 20 UC patients as controls. CD4+CD25+ T cells were isolated from PBMC with a direct immunofluorescence technique, using mice monoclonal antibodies namely FITC-labeled anti-CD4 and PE-labeled anti-CD25. In each patient, CD4+CD25+ T cells percentage in PBMC were studied by flow cytometry, and then the number of CD4+CD25+ T cells were calculated. RESULTS Twenty-seven UC patients with PSC and 20 UC patients without PSC as controls were enrolled in the present study. The percentage of CD4+CD25+ regulatory T cells among PBMC were significantly elevated in UC + PSC patients compared with UC patients without PSC (p = 0.04). CONCLUSIONS CD4+CD25+ T cells were found to be elevated in UC patients with PSC suggesting a partial role of activated T cell response in the disease pathophysiology. Our findings imply that CD4+CD25+ regulatory T cells may play a key role in the immunopathogenesis of UC-associated PSC and may affect the therapeutic management of these diseases.
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Affiliation(s)
- Murat Kekilli
- Department of Gastroenterology, Turkiye Yuksek Ihtisas Training and Research Hospital, Kızılay Sok. No: 2, 06100, Sıhhıye, Ankara, Turkey.
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47
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Abstract
Primary sclerosing cholangitis (PSC) is a chronic cholestatic liver disease. The etiology of this disorder is unknown and there are no effective medical therapies. PSC is associated with inflammatory bowel disease and an increased risk for hepatobiliary and colorectal malignancies. The aim of this review is to highlight the clinical features and diagnostic approach to patients with suspected PSC, characterize associated comorbidities, review screening strategies for PSC associated malignancies and review contemporary and future therapies.
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Jørgensen KK, Lindström L, Cvancarova M, Castedal M, Friman S, Schrumpf E, Foss A, Isoniemi H, Nordin A, Holte K, Rasmussen A, Bergquist A, Vatn MH, Boberg KM. Colorectal neoplasia in patients with primary sclerosing cholangitis undergoing liver transplantation: a Nordic multicenter study. Scand J Gastroenterol 2012; 47:1021-9. [PMID: 22577871 DOI: 10.3109/00365521.2012.685754] [Citation(s) in RCA: 42] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
OBJECTIVE Several studies have implicated primary sclerosing cholangitis (PSC) as an additional risk factor for colorectal neoplasia in inflammatory bowel disease (IBD). Some reports have indicated that the risk is even higher in PSC-IBD patients after liver transplantation (Ltx), but this issue is controversial. We aimed to compare the risk of colorectal neoplasia in PSC-IBD patients before and after Ltx and to identify risk factors for colorectal neoplasia post-transplant. MATERIAL AND METHODS In a multicenter study within the Nordic Liver Transplant Group, we assessed the risk of colorectal neoplasia by using the competing risk regression analysis. RESULTS Among the 439 PSC patients included, 353 (80%) had IBD at the time of Ltx and 15 (3%) patients developed de novo IBD post-Ltx. The median duration of IBD was 15 (0-50) years at the time of Ltx and follow-up after Ltx was 5 (0-20) years. Ninety-one (25%) PSC-IBD patients developed colorectal neoplasia. The cumulative risk of colorectal neoplasia was higher after than before Ltx (HR: 1.9, 95% CI: 1.3-2.9, p = 0.002). A multivariate analysis demonstrated aminosalicylates and ursodeoxycholic acid as significantly associated with an increased risk of colorectal neoplasia post-Ltx. Duration and activity of IBD did not significantly affect the risk of neoplasia. CONCLUSION The even higher risk of colorectal neoplasia in PSC-IBD patients after when compared with that of before Ltx underscores the importance of regular surveillance colonoscopies post-Ltx. The association of aminosalicylates and ursodeoxycholic acid to the development of colorectal neoplasia after Ltx should be further investigated.
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Affiliation(s)
- Kristin Kaasen Jørgensen
- Department of Transplantation Medicine, Division of Cancer, Surgery and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
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Navaneethan U, G K Venkatesh P, Lashner BA, Lopez R, Kiran RP, Shen B. Severity of primary sclerosing cholangitis and its impact on the clinical outcome of Crohn's disease. J Crohns Colitis 2012; 6:674-80. [PMID: 22398102 DOI: 10.1016/j.crohns.2011.11.020] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/01/2011] [Revised: 11/25/2011] [Accepted: 11/25/2011] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIM Crohn's disease (CD) is associated with primary sclerosing cholangitis (PSC). The aim of the study was to study the association between the severity of PSC and clinical outcome of CD, comparing the course of CD in patients with PSC not needing orthotopic liver transplantation (OLT) and those requiring OLT. METHODS A total of 41 patients with PSC and CD seen at the Cleveland Clinic between 1985 and 2011 were included in this study. Clinical and demographic variables were obtained regarding the outcome of CD in patients with and without OLT. RESULTS Patients with PSC-CD were divided into two groups: 20 without OLT (non-OLT) and 21 with OLT. 18 (85.7%) of patients in the OLT group had pancolitis in contrast to 14 (70%) in the non-OLT group. (p=0.22). There were no significant differences regarding duration of CD, but the duration of PSC was longer in the OLT group [16.0±7.8 vs. 10.3±6.4, p=0.01]. The OLT and non-OLT groups did not differ in the number of CD flares [0 (0, 0) vs. 0 (0, 5), p=0.28) and need for surgery for CD [(6 (28.6%) vs. 9 (45%), p=0.27]. Colon carcinoma and dysplasia were similar in the non-OLT and OLT groups [(4 (20%) vs. 3 (13.2%), p=0.52]. On Cox regression analysis, OLT for PSC [Hazards ratio (HR) 1.2 (95% confidence interval (C.I.): 0.38-3.7, p=0.79] did not impact the risk of colectomy. CONCLUSIONS In contrast to UC, severe PSC requiring OLT does not appear to impact the clinical outcome of CD.
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Affiliation(s)
- Udayakumar Navaneethan
- Department of Gastroenterology, Digestive Disease Institute, The Cleveland Clinic, Cleveland, OH, USA.
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50
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Tabibian JH, Lindor KD. Challenges of Cholangiocarcinoma Detection in Patients with Primary Sclerosing Cholangitis. JOURNAL OF ANALYTICAL ONCOLOGY 2012; 1:50-55. [PMID: 31897266 PMCID: PMC6939639 DOI: 10.6000/1927-7229.2012.01.01.7] [Citation(s) in RCA: 10] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
Primary sclerosing cholangitis (PSC) is a chronic, cholestatic, idiopathic liver disease characterized by fibro-obliterative inflammation of the hepatic bile ducts. In a clinically significant proportion of patients, PSC progresses to cirrhosis, end-stage liver disease, and in some cases, cholangiocarcinoma (CCA). The development of CCA in PSC is unpredictable, its surveillance and diagnosis complex, and its treatment options limited unless detected early. Herein we provide a focused review of the current literature regarding CCA surveillance in patients with PSC and discuss the diagnostic and management challenges that exist. Where evidence is limited, we present our perspective and approach as well as directions for future research.
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Affiliation(s)
- James H. Tabibian
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First St. SW, Rochester, MN 55905, USA
| | - Keith D. Lindor
- Executive Vice Provost, Health Solutions, Arizona State University, P.O. Box 877805, Tempe, AZ 85287-7805, USA
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