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1
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Fischer AK, Kroesen A, Büttner R. [Secondary malignant neoplasms with underlying Lynch syndrome and coincidental ulcerative colitis]. CHIRURGIE (HEIDELBERG, GERMANY) 2025; 96:415-420. [PMID: 40029372 PMCID: PMC12014831 DOI: 10.1007/s00104-025-02251-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 01/27/2025] [Indexed: 03/05/2025]
Affiliation(s)
- Anne Kristin Fischer
- Institut für Pathologie, Universität zu Köln, Kerpener Str. 62, 50937, Köln, Deutschland.
| | - Anton Kroesen
- Krankenhaus Porz am Rhein, Urbacher Weg 19, 51149, Köln, Deutschland
| | - Reinhard Büttner
- Institut für Pathologie, Universität zu Köln, Kerpener Str. 62, 50937, Köln, Deutschland
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2
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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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3
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S L, T RM, E TG, F C, E R, S S, C B, P P, M V. Hereditary colorectal cancer syndromes and inflammatory bowel disease: results from a registry-based study. Int J Colorectal Dis 2025; 40:24. [PMID: 39863767 PMCID: PMC11762763 DOI: 10.1007/s00384-025-04808-x] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 01/07/2025] [Indexed: 01/27/2025]
Abstract
PURPOSE In this study, we investigated the progression of high-grade dysplasia (HGD)/CRC in patients with hereditary colorectal cancer syndromes (HCSS) and concomitant inflammatory bowel diseases (IBDs). METHODS We described the natural history of a series of patients with confirmed diagnosis of hereditary colorectal cancer syndromes (HCCSs) and concomitant IBDs who were referred to the Hereditary Digestive Tumors Registry at the Fondazione IRCCS Istituto Nazionale dei Tumori of Milan. RESULTS Between January 1989 and April 2024, among 450 patients with APC-associated polyposis and 1050 patients with Lynch syndrome (LS), we identified six patients with IBDs (five with UC, one with ileal penetrating CD) and concomitant HCCSs (five with LS, one with APC-associated polyposis). Three patients developed CRC (two patients with stage IIA, and one with stage IIIA); in one patient, CRC occurred over a median follow-up of 12 months after IBD diagnosis, while in two, both conditions were diagnosed simultaneously. The median age at initial diagnosis of CRC was 33 years (range 27-41). Five patients (83.3%) underwent surgical procedures (three colonic resections for carcinoma and two for other reasons). Most of them progressed to precancerous or cancerous colonic lesions at a young age. Notably, all patients with CRC had a diagnosis of UC. CONCLUSION IBD patients with coexistent HCCSs can develop early CRC onset at an advanced stage. These patients should be always referred to tertiary referral centers for strict surveillance programs and early surgical management of advanced colorectal neoplastic lesions. Noninvasive biomarkers of neoplastic changes are advocated to further improve the management of IBD patients with HCCSs.
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Affiliation(s)
- Lauricella S
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy.
- Colorectal Surgery Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy.
| | - Ricci M T
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy
| | - Tontini G E
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
- Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy
| | - Cavallaro F
- Gastroenterology and Endoscopy Unit, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy
| | - Rausa E
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy
- Colorectal Surgery Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
| | - Signoroni S
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy
| | - Brignola C
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy
| | - Pasanisi P
- Nutrition Research and Metabolomics Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
| | - Vitellaro M
- Hereditary Digestive Tract Tumors Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Via Giacomo Venezian 1, 20133, Milan, Italy
- Colorectal Surgery Unit, Fondazione IRCCS Istituto Nazionale Dei Tumori, Milan, Italy
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Pricope DL, Grigoraş A, Costin CA, Amălinei C. Clinicopathological and molecular landscape in colorectal cancer associated with colorectal polyps and inflammatory bowel disease. ROMANIAN JOURNAL OF MORPHOLOGY AND EMBRYOLOGY = REVUE ROUMAINE DE MORPHOLOGIE ET EMBRYOLOGIE 2024; 65:745-757. [PMID: 39957036 PMCID: PMC11924904 DOI: 10.47162/rjme.65.4.21] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Accepted: 12/12/2024] [Indexed: 02/18/2025]
Abstract
Although inflammatory bowel disease (IBD) and colorectal polyps are considered as significant risk factors of colorectal cancer (CRC), the molecular mechanism associated with colorectal carcinogenesis is still explored. Unlike sporadic CRC, local persistent inflammation in IBD induces genetic and epigenetic alterations, leading to tumor development. Moreover, cumulative data indicate that colorectal polyps display a significant malignant potential. In this context, our study aimed to investigate the clinicopathological features of CRC associated with IBD and/or colorectal neoplastic polyps in a retrospective group of CRC cases. The clinical data and histopathological features of CRC cases have been collected from our files. Immunohistochemical examination of mismatch repair (MMR) proteins has been performed in a selected case. The study group comprised 40 patients, 72.5% men and 27.5% women, with a median age of 64.73±9.09 years. Out of the cases with double association, 62.5% of CRC cases displayed colorectal polyps, while 32.5% of patients were diagnosed with both CRC and IBD, which encompassed both ulcerative colitis (UC) and Crohn's disease (CD). Two patients included in our study group exhibited a triple association of IBD, colorectal polyps, and CRC, one of them showing defective MMR (dMMR) phenotype. Although our results provide significant data on the relationship between IBD, colorectal polyps, and colorectal carcinogenesis, future cohort studies are needed to improve our understanding on the complex mechanism of colorectal carcinogenesis, ultimately guiding improved prevention, diagnosis, and treatment strategies for these patients.
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Affiliation(s)
- Diana Lavinia Pricope
- Department of Morphofunctional Sciences I, Grigore T. Popa University of Medicine and Pharmacy, Iaşi, Romania; ,
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Brandaleone L, Dal Buono A, Gabbiadini R, Marcozzi G, Polverini D, Carvello M, Spinelli A, Hassan C, Repici A, Bezzio C, Armuzzi A. Hereditary Colorectal Cancer Syndromes and Inflammatory Bowel Diseases: Risk Management and Surveillance Strategies. Cancers (Basel) 2024; 16:2967. [PMID: 39272825 PMCID: PMC11394661 DOI: 10.3390/cancers16172967] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 08/15/2024] [Accepted: 08/22/2024] [Indexed: 09/15/2024] Open
Abstract
Background and aims: Hereditary colorectal cancer syndromes (HCCS), including familial adenomatous polyposis (FAP) and Lynch syndrome (LS), are the two most important high-risk conditions for colorectal cancer (CRC). Inflammatory bowel disease (IBD) increases the risk by two to six times compared with that in the general population. The intersection of these two conditions has rarely been documented in literature. We aimed to summarize the prevalence, pathogenesis, and current evidence-based management of IBD and HCCS and the underlying molecular mechanisms of accelerated carcinogenesis due to combined inflammation and genetic predisposition. Methods: PubMed and Scopus were searched until June 2024 to identify relevant studies investigating the epidemiology, pathogenesis, and management of IBD and coexisting hereditary CRC syndromes. Results: Co-occurrence of IBD and hereditary CRC syndromes is exceptionally uncommon. Individuals with LS and IBD tend to develop CRC at a younger age than those without IBD, with patients with ulcerative colitis facing particularly elevated risks. The interaction between mismatch deficiency and chronic inflammation requires further investigation.
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Affiliation(s)
- Luca Brandaleone
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
| | - Arianna Dal Buono
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Roberto Gabbiadini
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Giacomo Marcozzi
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
| | - Davide Polverini
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
| | - Michele Carvello
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- Colon and Rectal Surgery Division, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- Colon and Rectal Surgery Division, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Cesare Hassan
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- Endoscopy Unit, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Alessandro Repici
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
- Endoscopy Unit, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
| | - Cristina Bezzio
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
| | - Alessandro Armuzzi
- IBD Center, IRCCS Humanitas Research Hospital, Rozzano, 20089 Milan, Italy
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, 20072 Milan, Italy
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6
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Foda ZH, Dharwadkar P, Katona BW. Preventive strategies in familial and hereditary colorectal cancer. Best Pract Res Clin Gastroenterol 2023; 66:101840. [PMID: 37852714 DOI: 10.1016/j.bpg.2023.101840] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/14/2023] [Revised: 05/05/2023] [Accepted: 05/17/2023] [Indexed: 10/20/2023]
Abstract
Colorectal cancer is a leading cause of cancer-related deaths worldwide. While most cases are sporadic, a significant proportion of cases are associated with familial and hereditary syndromes. Individuals with a family history of colorectal cancer have an increased risk of developing the disease, and those with hereditary syndromes such as Lynch syndrome or familial adenomatous polyposis have a significantly higher risk. In these populations, preventive strategies are critical for reducing the incidence and mortality of colorectal cancer. This review provides an overview of current preventive strategies for individuals at increased risk of colorectal cancer due to familial or hereditary factors. The manuscript includes a discussion of risk assessment and genetic testing, highlighting the importance of identifying at-risk individuals and families. This review describes various preventive measures, including surveillance colonoscopy, chemoprevention, and prophylactic surgery, and their respective benefits and limitations. Together, this work highlights the importance of preventive strategies in familial and hereditary colorectal cancer.
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Affiliation(s)
- Zachariah H Foda
- The Sidney Kimmel Comprehensive Cancer Center and Department of Medicine, Division of Gastroenterology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
| | - Pooja Dharwadkar
- Division of Gastroenterology, Department of Medicine, University of California, San Francisco, CA, USA
| | - Bryson W Katona
- Division of Gastroenterology and Hepatology, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA.
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7
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Gené M, Cuatrecasas M, Amat I, Veiga JA, Fernández Aceñero MJ, Fusté Chimisana V, Tarragona J, Jurado I, Fernández-Victoria R, Martínez Ciarpaglini C, Alenda González C, Zac C, Ortega de la Obra P, Fernández-Figueras MT, Esteller M, Musulen E. Alterations in p53, Microsatellite Stability and Lack of MUC5AC Expression as Molecular Features of Colorectal Carcinoma Associated with Inflammatory Bowel Disease. Int J Mol Sci 2023; 24:8655. [PMID: 37240002 PMCID: PMC10217841 DOI: 10.3390/ijms24108655] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/29/2023] [Revised: 05/07/2023] [Accepted: 05/08/2023] [Indexed: 05/28/2023] Open
Abstract
Colitis-associated colorectal carcinoma (CAC) occurs in inflammatory bowel disease (IBD) because of the "chronic inflammation-dysplasia-cancer" carcinogenesis pathway characterized by p53 alterations in the early stages. Recently, gastric metaplasia (GM) has been described as the initial event of the serrated colorectal cancer (CRC) process, resulting from chronic stress on the colon mucosa. The aim of the study is to characterize CAC analyzing p53 alterations and microsatellite instability (MSI) to explore their relationship with GM using a series of CRC and the adjacent intestinal mucosa. Immunohistochemistry was performed to assess p53 alterations, MSI and MUC5AC expression as a surrogate for GM. The p53 mut-pattern was found in more than half of the CAC, most frequently stable (MSS) and MUC5AC negative. Only six tumors were unstable (MSI-H), being with p53 wt-pattern (p = 0.010) and MUC5AC positive (p = 0.005). MUC5AC staining was more frequently observed in intestinal mucosa, inflamed or with chronic changes, than in CAC, especially in those with p53 wt-pattern and MSS. Based on our results, we conclude that, as in the serrated pathway of CRC, in IBD GM occurs in inflamed mucosa, persists in those with chronic changes and disappears with the acquisition of p53 mutations.
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Affiliation(s)
- Míriam Gené
- Pathology Department, Hospital Universitari Joan XXIII, 43005 Tarragona, Spain;
- Surgery Department, Programme of Surgery and Morphological Sciences, Universitat Autònoma de Barcelona (UAB), 08193 Barcelona, Spain
| | - Míriam Cuatrecasas
- Pathology Department, Hospital Clínic de Barcelona, Universitat de Barcelona (UB), 08007 Barcelona, Spain;
- School of Medicine, Campus Clínic, Universitat de Barcelona (UB), 08036 Barcelona, Spain
| | - Irene Amat
- Pathology Department, Complejo Hospitalario de Navarra, 31008 Navarra, Spain;
| | - Jesús Alberto Veiga
- Pathology Department, Complejo Hospitalario Universitario de Ferrol, 15405 Ferrol, Spain;
| | | | | | - Jordi Tarragona
- Pathology Department, Hospital Universitari Arnau de Vilanova, 25198 Lleida, Spain;
| | - Ismael Jurado
- Pathology Department, Consorci Sanitari de Terrassa, 08227 Terrassa, Spain;
| | | | - Carolina Martínez Ciarpaglini
- Pathology Department, Hospital Clínico Universitario de Valencia, Valencia INCLIVA-Instituto de Investigación Sanitaria, Universidad de Valencia, 46010 Valencia, Spain;
| | - Cristina Alenda González
- Pathology Department, Hospital General Universitario Dr. Balmis, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), 03010 Alicante, Spain;
| | - Carlos Zac
- Pathology Department, Hospital Universitari i Politècnic La Fe, 46026 Valencia, Spain;
| | | | - María Teresa Fernández-Figueras
- Pathology Department, Hospital Universitari General de Catalunya-Grupo QuironSalud, Sant Cugat del Vallès, 08195 Barcelona, Spain;
- School of Medicine, Campus Sant Cugat del Vallès, Universitat Internacional de Catalunya (UIC), Sant Cugat del Vallès, 08017 Barcelona, Spain
| | - Manel Esteller
- Institut de Recerca contra la Leucèmia Josep Carreras (IJC), Badalona, 08916 Barcelona, Spain;
- Institució Catalana de Recerca i Estudis Avançats (ICREA), 08010 Barcelona, Spain
- Faculty of Medicine and Health Sciences, Department of Physiological Sciences, Universitat de Barcelona (UB), 08007 Barcelona, Spain
- Centro de Investigación Biomédica en Red Cáncer (CIBERONC), 28029 Madrid, Spain
| | - Eva Musulen
- Pathology Department, Hospital Universitari General de Catalunya-Grupo QuironSalud, Sant Cugat del Vallès, 08195 Barcelona, Spain;
- Institut de Recerca contra la Leucèmia Josep Carreras (IJC), Badalona, 08916 Barcelona, Spain;
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Ayeni AA, Waterland P, Evans M, Singhal S, Patel RK, Akingboye A. Case Report: Multiple colorectal cancers in a patient with Ulcerative colitis and Lynch syndrome: Is there a role for prophylactic colectomy? A short report and review of literature. Front Oncol 2022; 12:1031606. [PMID: 36620534 PMCID: PMC9815500 DOI: 10.3389/fonc.2022.1031606] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2022] [Accepted: 11/24/2022] [Indexed: 12/24/2022] Open
Abstract
It is a known fact that Lynch syndrome (LS) and Ulcerative colitis (UC) are individually associated with increased risk of colorectal cancer. While there is no conclusive evidence to demonstrate a cumulative risk when these two conditions coexist, available data suggest early onset and synchronous cancers are synonymous to this group. We have reported an unusual case of multiple synchronous colorectal cancers in a young man with ulcerative colitis and Lynch syndrome also known as Hereditary Nonpolyposis Colorectal Cancer (HNPCC) gene mutation. We propose that conducting a detailed genetic mutation profile in LS patients may play a key role in guiding the intensity of endoscopic surveillance and that a concerted, pragmatic, patient guided approach should be adopted on the subject of prophylactic colectomy when UC and LS co-exist.
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Affiliation(s)
- Adewale Adeoba Ayeni
- Department of General Surgery, The Dudley Group Foundation NHS Trust, Russells Hall Hospital, Dudley, West Midlands
| | - Peter Waterland
- Department of General Surgery, The Dudley Group Foundation NHS Trust, Russells Hall Hospital, Dudley, West Midlands
| | - Matthew Evans
- Department of Pathology, New Cross Hospital, Wolverhampton, United Kingdom
| | - Shika Singhal
- Department of Pathology, New Cross Hospital, Wolverhampton, United Kingdom
| | - Rajan Kumar Patel
- Department of General Surgery, The Dudley Group Foundation NHS Trust, Russells Hall Hospital, Dudley, West Midlands
| | - Akinfemi Akingboye
- Department of General Surgery, The Dudley Group Foundation NHS Trust, Russells Hall Hospital, Dudley, West Midlands,*Correspondence: Akinfemi Akingboye,
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9
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Barberio B, Savarino E, Verstockt B, Fumery M, Pugliese D, Bertani L, Buda A, Dragoni G, Goren I, Laish I, Spinelli A, Teich N, Truyens M, Ellul P. Hereditary Colorectal Cancer Syndromes and Inflammatory Bowel Diseases: an ECCO CONFER Multicentre Case Series. J Crohns Colitis 2022; 16:1845-1852. [PMID: 35771951 DOI: 10.1093/ecco-jcc/jjac094] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND Hereditary colorectal cancer syndromes [HCCS] are rare polyposis or nonpolyposis syndromes with a higher risk of developing colorectal cancer [CRC]. Coexisting inflammatory bowel disease [IBD], including ulcerative colitis [UC] and Crohn's disease [CD], with HCCS is exceedingly rare and presumably increases the risk of early-onset CRC. METHODS This was a multicentre case series performed as a part of the European Crohn's and Colitis Organisation [ECCO] Collaborative Network of Exceptionally Rare case reports [CONFER] project. RESULTS This report includes 26 patients with IBD (10 UC, 15 CD, and one with IBD unclassified [IBD-U]) and concomitant HCCS. Among these 26 patients([median age 33 years, interquartile range [IQR] 20-44], 15 [57.7%] were males, 24 [92.3%] Caucasians, and two [7.7%] of Arab origin. HCCS was diagnosed before the IBD diagnosis in 11 patients [42.3%], after diagnosis of IBD in 11 patients [42.3%], and concurrently in four patients [15.4%]. Sixteen patients had Lynch syndrome, seven had familial adenomatous polyposis [FAP], two had MYH-associated polyposis [MAP], and one had attenuated FAP [AFAP]. The most frequent genetic mutations were those of APC [n = 7] and MLH1 [n = 7]. Overall, CRC developed in 38.5% of patients [n = 10]: in four patients [40%] after IBD diagnosis, in four [40%] patients before IBD diagnosis, and in two patients the two conditions were diagnosed simultaneously. Eighteen [69.2%] patients underwent colectomy or abdominal surgery: nine patients due to CRC diagnosis, five patients preventively due to the underlying HCCS, three due to the underlying HCCS and concomitant active IBD disease, and one patient because of active IBD disease. One patient died due to CRC. CONCLUSIONS To date, this is the largest case series of patients with IBD and HCCS. The most frequent diagnosis of HCCS associated with IBD was Lynch syndrome. These data demonstrate the high malignancy rate and surgical intervention rate in this IBD cohort, despite the endoscopic surveillance. The optimal medical approach still needs to be addressed.
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Affiliation(s)
- Brigida Barberio
- Department of Surgery Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Edoardo Savarino
- Department of Surgery Oncology and Gastroenterology, University of Padova, Padova, Italy
| | - Bram Verstockt
- Department of Gastroenterology and Hepatology, University Hospital, Leuven, Belgium
- Department of Chronic Disease and Metabolism, KU Leuven, Leuven, Belgium
| | - Mathurin Fumery
- Gastroenterology Unit, Amiens University Hospital, Amiens, France
| | - Daniela Pugliese
- Department of Medical and Surgical Sciences, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy
| | | | - Andrea Buda
- Department of Gastrointestinal Oncological Surgery, S. Maria del Prato- Hospital Feltre, Feltre, Italy
| | - Gabriele Dragoni
- Department of Gastroenterology, Careggi University Hospital, Florence, Italy
| | - Idan Goren
- Division of Gastroenterology, Rabin Medical Centre, Petah Tikva, Israel
| | - Ido Laish
- Gastroenterology Unit, Sheba Medical Centre, Tel Hashomer, Israel
| | - Antonino Spinelli
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy
- Department of Surgery, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Niels Teich
- Internistische Gemeinschaftspraxis für Verdauungs- und Stoffwechselkrankheiten IGVS, University Hospital of Leipzig, Leipzig, Germany
| | - Marie Truyens
- Department of Gastroenterology, Ghent University Hospital, Ghent, Belgium
| | - Pierre Ellul
- Department of Medicine, Division of Gastroenterology, Mater Dei Hospital, Msida, Malta
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10
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Risk of Metachronous Colorectal Cancer in Lynch Syndrome: Who Needs an Extended Resection? SURGERIES 2022. [DOI: 10.3390/surgeries3030020] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/16/2022] Open
Abstract
Lynch syndrome (LS) is the most common genetic condition associated with early-onset colorectal cancer. It is inherited in an autosomal dominant fashion. The increased cancer risk is due to a germline mutation in one of the mismatch repair (MMR) genes (MLH1, MSH2, MSH6, and PMS2) or the EPCAM gene. This leads to a deficient DNA mismatch repair mechanism, resulting in the accumulation of nucleotide changes and microsatellite instability, providing phenotypical evidence that MMR is not functioning normally. LS is associated with a high risk of early-onset colorectal cancer and recurrence. Thus, when undergoing surgery for primary colorectal cancer, extended resection should be discussed with the patient. This review provides an overview of current surgical risk-reducing strategies in LS-associated colorectal cancer. Surgical treatment for LS carriers with colorectal cancer needs to be highly individualized, based on patient and disease characteristics. Strategies are presented to guide decision making in pathologic MMR gene mutation carriers undergoing surgery for colorectal cancer.
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11
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Núñez F P, Quera R, Rubin DT. Endoscopic colorectal cancer surveillance in inflammatory bowel disease: Considerations that we must not forget. World J Gastrointest Endosc 2022; 14:85-95. [PMID: 35316980 PMCID: PMC8908328 DOI: 10.4253/wjge.v14.i2.85] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2021] [Revised: 08/02/2021] [Accepted: 01/23/2022] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease (IBD), encompassing Crohn's disease and ulcerative colitis, is a chronic immune-mediated inflammatory disease that primarily affects the gastrointestinal tract and is characterized by periods of activity and remission. The inflammatory activity of the disease involving the colon and rectum increases the risk of colorectal cancer (CRC) over the years. Although prevention strategies are evolving, regular surveillance for early detection of neoplasia as a secondary prevention strategy is paramount in the care of IBD patients. In this review article, we discuss the current evidence of the risks of developing CRC and evaluate the best available strategies for screening and surveillance, as well as future opportunities for cancer prevention.
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Affiliation(s)
- Paulina Núñez F
- Universidad de los Andes, Digestive Disease Center, Inflammatory Bowel Disease Program, Clinica, Santiago 7620157, RM, Chile
- Department of Gastroenterology, Hospital San Juan de Dios. Universidad de Chile, Santiago 7701230, RM, Chile
| | - Rodrigo Quera
- Universidad de los Andes, Digestive Disease Center, Inflammatory Bowel Disease Program, Clinica, Santiago 7620157, RM, Chile
| | - David T Rubin
- Medicine Inflammatory Bowel Disease Center, University of Chicago, Chicago, IL 60637, United States
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12
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Faisal MS, Burke CA, Liska D, Lightner AL, Leach B, O’Malley M, LaGuardia L, Click B, Achkar JP, Kalady M, Church JM, Mankaney G. Association of cancer with comorbid inflammatory conditions and treatment in patients with Lynch syndrome. World J Clin Oncol 2022; 13:49-61. [PMID: 35116232 PMCID: PMC8790302 DOI: 10.5306/wjco.v13.i1.49] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 08/12/2021] [Accepted: 12/23/2021] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND Individuals with Lynch syndrome (LS) and hereditary non-polyposis colorectal cancer (HNPCC) are at increased risk of both colorectal cancer and other cancers. The interplay between immunosuppression, a comorbid inflammatory condition (CID), and HNPCC on cancer risk is unclear.
AIM To evaluate the impact of CIDs, and exposure to monoclonal antibodies and immunomodulators, on cancer risk in individuals with HNPCC.
METHODS Individuals prospectively followed in a hereditary cancer registry with LS/HNPCC with the diagnosis of inflammatory bowel disease or rheumatic disease were identified. We compared the proportion of patients with cancer in LS/HNPCC group with and without a CID. We also compared the proportion of patients who developed cancer following a CID diagnosis based upon exposure to immunosuppressive medications.
RESULTS A total of 21 patients with LS/HNPCC and a CID were compared to 43 patients with LS/HNPCC but no CID. Cancer occurred in 84.2% with a CID compared to 76.7% without a CID (P = 0.74) with no difference in age at first cancer diagnosis 45.5 ± 14.6 vs 43.8 ± 7.1 years (P = 0.67). LS specific cancers were diagnosed in 52.4% with a CID vs 44.2% without a CID (P = 0.54). Nine of 21 (42.9%) patients were exposed to biologics or immunomodulators for the treatment of their CID. Cancer after diagnosis of CID was seen in 7 (77.8%) of exposed individuals vs 5 (41.7%) individuals unexposed to biologics/immunomodulators (P = 0.18). All 7 exposed compared to 3/5 unexposed developed a LS specific cancer. The exposed and unexposed groups were followed for a median 10 years and 8.5 years, respectively. The hazard ratio for cancer with medication exposure was 1.59 (P = 0.43, 95%CI: 0.5-5.1).
CONCLUSION In patients with LS/HNPCC, the presence of a concurrent inflammatory condition, or use of immunosuppressive medication to treat the inflammatory condition, might not increase the rate of cancer occurrence in this limited study.
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Affiliation(s)
- Muhammad S Faisal
- Department of Internal Medicine, Cleveland Clinic Foundation, Cleveland, OH 44195, United States
| | - Carol A Burke
- Department of Gastroenterology and Hepatology, Cleveland Clinic, Cleveland, OH 44195, United States
| | - David Liska
- Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Amy L Lightner
- Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Brandie Leach
- Center for Personalized Genetic Healthcare, Genomic Medicine Institute, Cleveland, OH 44195, United States
| | - Margaret O’Malley
- Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Lisa LaGuardia
- Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Benjamin Click
- Department of Gastroenterology, Hepatology, & Nutrition, Cleveland Clinic, Cleveland, OH 44195, United States
| | - JP Achkar
- Center for Inflammatory Bowel Disease, Department of Gastroenterology, Hepatology and Nutrition, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Matthew Kalady
- Department of Colorectal Surgery, Ohio State University, Columbus, OH 43210, United States
| | - JM Church
- Department of Colorectal Surgery, Cleveland Clinic, Cleveland, OH 44195, United States
| | - Gautam Mankaney
- Department of Gastroenterology and Hepatology, Virginia Mason Franciscan Health, Seattle, WA 98101, United States
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13
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Durhuus JA, Therkildsen C, Kallemose T, Nilbert M. Colorectal cancer in adolescents and young adults with Lynch syndrome: a Danish register-based study. BMJ Open 2021; 11:e053538. [PMID: 34911717 PMCID: PMC8679060 DOI: 10.1136/bmjopen-2021-053538] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022] Open
Abstract
OBJECTIVE To assess clinicopathological predictors and prognosis in early-onset colorectal cancer (CRC) in Lynch syndrome with comparison to patients diagnosed from age 40 and up. DESIGN National, retrospective register-based case-control study. SETTING Danish national hereditary CRC register. PARTICIPANTS Individuals with Lynch syndrome diagnosed with CRC from January 1950 to June 2020. The analysis was based on 215 early-onset CRCs diagnosed between 15 and 39 years of age and 574 CRCs diagnosed at age 40-88 years. MAIN OUTCOME MEASURES Clinical and histopathological characteristics and survival. Confounding variables were analysed by Cox analysis. RESULTS 27.2% of the tumours in the Danish Lynch syndrome cohort were diagnosed under age 40. Disease-predisposing alterations in MLH1 and MSH2 were overrepresented in the age 15-39 cohort compared with patients diagnosed over age 40. CRCs diagnosed under age 40 showed an adverse stage distribution with 36.2% stage III-IV tumours compared with 25.8% in the over age 40 group. However, young patients diagnosed with early-stage tumours did have a significantly better prognosis compared with early-stage tumours in the older age group. CONCLUSIONS Early-onset CRC in Lynch syndrome is primarily linked to alterations in MLH1 and MSH2 and displays an adverse stage distribution. These observations serve as a reminder of surveillance, symptom awareness and rapid diagnostic handling of CRC in young adults with Lynch syndrome.
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Affiliation(s)
- Jon Ambæk Durhuus
- Department of Clinical Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark
| | - Christina Therkildsen
- Department of Clinical Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark
- The Danish HNPCC Register, Gastro Unit, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark
| | - Thomas Kallemose
- Department of Clinical Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark
| | - Mef Nilbert
- Department of Clinical Research, Copenhagen University Hospital - Amager and Hvidovre, Copenhagen, Denmark
- Danish Cancer Society Research Center, Copenhagen, Denmark
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14
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Seppälä TT, Latchford A, Negoi I, Sampaio Soares A, Jimenez‐Rodriguez R, Sánchez‐Guillén L, Evans DG, Ryan N, Crosbie EJ, Dominguez‐Valentin M, Burn J, Kloor M, von Knebel Doeberitz M, van Duijnhoven FJB, Quirke P, Sampson JR, Møller P, Möslein G, the European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP). European guidelines from the EHTG and ESCP for Lynch syndrome: an updated third edition of the Mallorca guidelines based on gene and gender. Br J Surg 2021; 108:484-498. [PMID: 34043773 PMCID: PMC10364896 DOI: 10.1002/bjs.11902] [Citation(s) in RCA: 138] [Impact Index Per Article: 34.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/24/2020] [Revised: 05/16/2020] [Accepted: 06/14/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Lynch syndrome is the most common genetic predisposition for hereditary cancer but remains underdiagnosed. Large prospective observational studies have recently increased understanding of the effectiveness of colonoscopic surveillance and the heterogeneity of cancer risk between genotypes. The need for gene- and gender-specific guidelines has been acknowledged. METHODS The European Hereditary Tumour Group (EHTG) and European Society of Coloproctology (ESCP) developed a multidisciplinary working group consisting of surgeons, clinical and molecular geneticists, pathologists, epidemiologists, gastroenterologists, and patient representation to conduct a graded evidence review. The previous Mallorca guideline format was used to revise the clinical guidance. Consensus for the guidance statements was acquired by three Delphi voting rounds. RESULTS Recommendations for clinical and molecular identification of Lynch syndrome, surgical and endoscopic management of Lynch syndrome-associated colorectal cancer, and preventive measures for cancer were produced. The emphasis was on surgical and gastroenterological aspects of the cancer spectrum. Manchester consensus guidelines for gynaecological management were endorsed. Executive and layperson summaries were provided. CONCLUSION The recommendations from the EHTG and ESCP for identification of patients with Lynch syndrome, colorectal surveillance, surgical management of colorectal cancer, lifestyle and chemoprevention in Lynch syndrome that reached a consensus (at least 80 per cent) are presented.
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Affiliation(s)
- T T Seppälä
- Department of Surgery, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland
- Department of Surgical Oncology, Johns Hopkins Hospital, Baltimore Maryland, USA
| | - A Latchford
- Department of Cancer and Surgery, Imperial College London, UK
- St Mark's Hospital, London North West Healthcare NHS Trust, London, UK
| | - I Negoi
- Department of Surgery, Emergency Hospital of Bucharest, Carol Davila University of Medicine and Pharmacy, Bucharest, Romania
| | | | - R Jimenez‐Rodriguez
- Department of Surgery, Hospital Universitario Virgen del Rocío, Seville, Spain
| | - L Sánchez‐Guillén
- Colorectal Unit, Department of General Surgery, Elche University General Hospital Elche, Alicante, Spain
| | - D G Evans
- Manchester Centre for Genomic Medicine, Division of Evolution and Genomic Sciences, University of Manchester, Manchester University Hospitals NHS Foundation Trust, UK
| | - N Ryan
- Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, UK
- Centre for Academic Women's Health, University of Bristol, Bristol, UK
| | - E J Crosbie
- Division of Cancer Sciences, Faculty of Biology, Medicine and Health, University of Manchester, St Mary's Hospital, Manchester, UK
| | - M Dominguez‐Valentin
- Department of Tumour Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
| | - J Burn
- Faculty of Medical Sciences, Newcastle Upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK
| | - M Kloor
- Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Germany
- Cooperation Unit Applied Tumour Biology, German Cancer Research Centre, Heidelberg, Germany
| | - M von Knebel Doeberitz
- Department of Applied Tumour Biology, Institute of Pathology, University Hospital Heidelberg, Germany
- Cooperation Unit Applied Tumour Biology, German Cancer Research Centre, Heidelberg, Germany
| | - F J B van Duijnhoven
- Division of Human Nutrition and Health, Wageningen University and Research, Wageningen, the Netherlands
| | - P Quirke
- Pathology and Data Analytics, School of Medicine, University of Leeds, Leeds, UK
| | - J R Sampson
- Institute of Medical Genetics, Division of Cancer and Genetics, Cardiff University School of Medicine, Heath Park, Cardiff, UK
| | - P Møller
- Department of Tumour Biology, Norwegian Radium Hospital, Oslo University Hospital, Oslo, Norway
- University of Witten/Herdecke, Witten, Germany
| | - G Möslein
- Centre for Hereditary Tumours, Bethesda Hospital, Duisburg, Germany
- University of Witten/Herdecke, Witten, Germany
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15
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Kamarádová K, Vošmiková H, Rozkošová K, Ryška A, Tachecí I, Laco J. Morphological, immunohistochemical and molecular features of inflammatory bowel disease associated colorectal carcinoma and associated mucosal lesions - Single institution experience. Pathol Res Pract 2019; 215:730-737. [PMID: 30679085 DOI: 10.1016/j.prp.2019.01.010] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/21/2018] [Revised: 12/23/2018] [Accepted: 01/05/2019] [Indexed: 02/08/2023]
Abstract
BACKGROUND Patients with inflammatory bowel disease (IBD) - ulcerative colitis (UC) and Crohn's disease (CD) have an elevated risk of developing colorectal carcinoma (CRC). Major risk factor in IBD patients is the continuous chronic inflammation leading to development of dysplasia and carcinoma. Nevertheless, other types of non-conventional but suspicious mucosal changes serrated change/dysplasia, NOS and villous hypermucinous change, have also been reported in IBD patients. Preneoplastic potential of these lesions is still not well elucidated. AIMS The aim of this study was identification of IBD-associated CRCs focusing on finding related precursor lesions in the surgical specimen or in archival biopsy samples followed by a detailed morphological, immunohistochemical and molecular evaluation. For the purpose of the study the mucosal lesions were divided into conventional IBD-associated dysplasia and non-conventional lesions that were merged under a provisory term of putative preneoplastic lesions (PPL). METHODS A total of 309 consecutive IBD colectomy specimens diagnosed during a 10-year period were reviewed. Detailed morphological evaluation, immunohistochemical analysis of mismatch repair (MMR) proteins, p53 and O6-methylguanine DNA methyltransferase (MGMT) expression and molecular analysis for KRAS, NRAS and BRAF gene mutation were performed in the retrieved CRC cases as well as in the detected dysplasia and PPLs of these patients. RESULTS We identified 11 cases of morphologically heterogenous IBD-associated CRCs, occurring in 5 males and 6 females, aged 26-79 years (mean 44 years). A total of 22 mucosal lesions were revealed in 8 CRC patients comprising conventional IBD-associated dysplasia (4 lesions), PPLs as serrated change/dysplasia NOS (11 lesions), villous hypermucinous change (5 lesions), and two true serrated lesions (one sessile serrated adenoma and one traditional serrated adenoma). More than one type of lesion was found in 6 patients. Seven CRC cases harbored mutation of KRAS/NRAS and one case of BRAF. Two patients with KRAS-mutated CRC showed the same mutation in PPL in the same specimen (one serrated change NOS and one TSA with high-grade dysplasia). Similarly, one BRAF-mutated carcinoma case presented the same mutation in serrated change/dysplasia, NOS in the same specimen. Of the CRCs, two showed deficient MMR system profile, six presented with loss of MGMT expression, and six showed aberrant p53 expression. PPLs showed deficient MGMT expression (14 cases) and aberrant p53 (10 cases) as well. CONCLUSION IBD-associated CRCs are very heterogeneous entities. Besides conventional IBD-related dysplasia, other types of mucosal lesions may be associated with long lasting IBD and CRC e.g. villous hypermucinous change and serrated change/dysplasia, NOS. Since these lesions share certain genetic or immunohistochemical changes with the related CRC, a suspicion is raised that these lesions may also have preneoplastic potential. Awareness of these changes is necessary to prevent their missing and under-reporting, and further studies of these lesions should be carried out.
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Affiliation(s)
- Kateřina Kamarádová
- The Fingerland Department of Pathology, Charles University Faculty of Medicine and University Hospital Hradec Králové, Sokolská 581, Hradec Králové, 500 03, Czech Republic.
| | - Hana Vošmiková
- The Fingerland Department of Pathology, Charles University Faculty of Medicine and University Hospital Hradec Králové, Sokolská 581, Hradec Králové, 500 03, Czech Republic.
| | - Kateřina Rozkošová
- The Fingerland Department of Pathology, Charles University Faculty of Medicine and University Hospital Hradec Králové, Sokolská 581, Hradec Králové, 500 03, Czech Republic.
| | - Aleš Ryška
- The Fingerland Department of Pathology, Charles University Faculty of Medicine and University Hospital Hradec Králové, Sokolská 581, Hradec Králové, 500 03, Czech Republic.
| | - Ilja Tachecí
- 2nd Department of Internal Medicine-Gastroenterology, Charles University Faculty of Medicine and University Hospital Hradec Králové, Sokolská 581, Hradec Králové, 500 03, Czech Republic.
| | - Jan Laco
- The Fingerland Department of Pathology, Charles University Faculty of Medicine and University Hospital Hradec Králové, Sokolská 581, Hradec Králové, 500 03, Czech Republic.
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16
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Kaimakliotis P, Giardiello F, Eze O, Truta B. A rare case of Crohn's ileitis in a patient with constitutional mismatch repair deficiency. Ann Gastroenterol 2017; 30:370-372. [PMID: 28469372 PMCID: PMC5411392 DOI: 10.20524/aog.2017.0129] [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: 11/27/2016] [Accepted: 01/30/2017] [Indexed: 11/16/2022] Open
Abstract
Constitutional mismatch repair deficiency (CMMRD), a variant of Lynch syndrome, is a rare disease characterized by café-au-lait spots, oligopolyposis, glioblastoma and lymphoma. A 24-year-old male, under surveillance for CMMRD, developed Crohn’s ileitis after total colectomy with end ileostomy for colorectal cancer and failed to respond to oral corticosteroids. The patient underwent induction and maintenance of remission with vedolizumab infusions. We report the first patient with CMMRD developing Crohn’s disease. The choice of immunosuppressive therapy in these patients is challenging and needs to be made according to their risk for malignancy.
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Affiliation(s)
- Pavlos Kaimakliotis
- Department of Medicine (Pavlos Kaimakliotis, Francis Giardiello, Brindusa Truta)
| | - Francis Giardiello
- Department of Medicine (Pavlos Kaimakliotis, Francis Giardiello, Brindusa Truta)
| | - Ogechukwu Eze
- Pathology (Ogechukwu Eze), Johns Hopkins University, School of Medicine, USA
| | - Brindusa Truta
- Department of Medicine (Pavlos Kaimakliotis, Francis Giardiello, Brindusa Truta)
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17
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Derikx LAAP, Smits LJT, van Vliet S, Dekker E, Aalfs CM, van Kouwen MCA, Nagengast FM, Nagtegaal ID, Hoogerbrugge N, Hoentjen F. Colorectal Cancer Risk in Patients With Lynch Syndrome and Inflammatory Bowel Disease. Clin Gastroenterol Hepatol 2017; 15:454-458.e1. [PMID: 27521512 DOI: 10.1016/j.cgh.2016.08.005] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/06/2016] [Revised: 07/18/2016] [Accepted: 08/03/2016] [Indexed: 02/07/2023]
Abstract
Lynch syndrome and inflammatory bowel diseases (IBD) are associated with an increased risk of colorectal cancer (CRC). However, it is not clear whether the risk of CRC is even higher for patients with a combination of Lynch syndrome and IBD. We investigated the risk for CRC in this subgroup by establishing a Lynch syndrome cohort from the Radboud University Medical Center (Nijmegen, The Netherlands) and the Academic Medical Center (Amsterdam, The Netherlands). Patients with heterozygous germline mutations in MLH1, MSH2 (and EPCAM deletion-mediated MSH2 methylation), MSH6, or PMS2 who were tested and/or treated from 1998 through 2014 were included. Patients who developed IBD were identified by linkage of this cohort to the Dutch nationwide Pathology Registry (PALGA). Subsequently, we compared the risk of CRC between Lynch syndrome patients with IBD and without IBD. Of 1046 patients with Lynch syndrome, 15 developed IBD (1.4%). Patients with Lynch syndrome and IBD were significantly younger (median age, 38.0 y) than patients with Lynch syndrome without IBD (median age, 52.0 y; P = .001). Nevertheless, a similar proportion of patients in each group developed CRC: 4 of the 15 patients (26.7%) with Lynch syndrome and IBD compared with 311 of the 1031 patients (30.2%) with Lynch syndrome without IBD. Patients with Lynch syndrome and IBD developed CRC at a younger age (median age, 36.0 y) than patients with Lynch syndrome without IBD (median age, 46.0 y; P = .045). However, the cumulative incidence of CRC was similar between groups (P = .121). All patients with Lynch syndrome and IBD who developed CRC had ulcerative colitis, producing a higher cumulative incidence of CRC for this IBD subgroup (P < .001). In conclusion, patients with Lynch syndrome and IBD develop CRC risk at a younger age than patients without IBD; patients with ulcerative colitis are at especially high risk.
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Affiliation(s)
- Lauranne A A P Derikx
- Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Lisa J T Smits
- Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Shannon van Vliet
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Evelien Dekker
- Department of Gastroenterology and Hepatology, Academic Medical Center, Amsterdam, The Netherlands
| | - Cora M Aalfs
- Department of Human Genetics, Academic Medical Center, Amsterdam, The Netherlands
| | - Mariëtte C A van Kouwen
- Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Fokko M Nagengast
- Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Iris D Nagtegaal
- Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Nicoline Hoogerbrugge
- Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands
| | - Frank Hoentjen
- Inflammatory Bowel Disease Center, Department of Gastroenterology and Hepatology, Radboud University Medical Center, Nijmegen, The Netherlands.
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