|
1
|
Mark-Christensen A, Kristiansen EB, Myrelid P, Laurberg S, Erichsen R. Appendectomy and Risk of Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: A Nationwide Population-based Cohort Study. Inflamm Bowel Dis 2024; 30:877-883. [PMID: 37523678 DOI: 10.1093/ibd/izad141] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Indexed: 08/02/2023]
Abstract
BACKGROUND The aim of this study was to examine the association between appendectomy and advanced colorectal neoplasia (aCRN) in patients with inflammatory bowel disease (IBD). METHODS Inflammatory bowel disease patients diagnosed in Denmark in the period 1977 to 2017 were identified from the Danish National Patient Registry. Inflammatory bowel disease patients who underwent appendectomy were matched with up to 10 IBD patients without appendectomy and followed until aCRN, death, or emigration. Absolute risks of aCRN were calculated, treating death and bowel resections as competing risks. Stratified Cox regression was used to calculate adjusted hazard ratios (aHRs) of aCRN, comparing IBD patients with appendectomy to IBD patients without appendectomy. RESULTS We identified 3789 IBD patients with appendectomy and 37 676 IBD patients without appendectomy. A total of 573 patients (1.4%) developed aCRN, with an absolute risk of aCRN at 20 years of 4.9% (95% confidence interval [CI], 2.9%-7.7%) for ulcerative colitis (UC) patients with appendectomy after UC diagnosis compared with 2.8% (95% CI, 2.3%-3.3%) for UC patients without appendectomy. Appendectomy after UC was associated with an increased rate of aCRN 5 to 10 years (aHR, 2.5; 95% CI, 1.1-5.5) and 10 to 20 years after appendectomy (aHR, 2.3; 95% CI, 1.0-5.5). Appendectomy prior to UC diagnosis was not associated with an increased rate of aCRN, and Crohn's disease was not associated with the rate of aCRN, regardless of timing or histological diagnosis of the appendix specimen. CONCLUSIONS Although appendectomy may have a positive effect on the clinical course of UC, our study suggests that this may come at the expense of a higher risk of aCRN.
Collapse
Affiliation(s)
- Anders Mark-Christensen
- Department of Clinical Epidemiology, Aarhus University Hospital, Denmark
- Department of Surgery, Svendborg Hospital OUH, Denmark
| | | | - Pär Myrelid
- Department of Surgery, Linköping University Hospital, Linköping, Sweden
- Department of Biomedical and Clinical Sciences, Division of Surgery, Linköping University, Linköping, Sweden
| | - Søren Laurberg
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - Rune Erichsen
- Department of Clinical Epidemiology, Aarhus University Hospital, Denmark
- Department of Surgery, Randers Regional Hospital, Randers, Denmark
| |
Collapse
|
|
2
|
Williams H, Steinhagen RM. Historical Perspectives: Malignancy in Crohn's Disease and Ulcerative Colitis. Clin Colon Rectal Surg 2024; 37:5-12. [PMID: 38188065 PMCID: PMC10769586 DOI: 10.1055/s-0043-1762557] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/09/2024]
Abstract
While both Crohn' disease (CD) and ulcerative colitis (UC) are known to predispose patients to certain intestinal malignancies, the exact mechanism of carcinogenesis remains unknown and optimal screening guidelines have not been established. This article will explore the history of our understanding of intestinal malignancy in inflammatory bowel disease (IBD). To contextualize the medical community's difficulty in linking each condition to cancer, the first section will review the discovery of CD and UC. Next, we discuss early attempts to define IBD's relationship with small bowel adenocarcinoma and colorectal cancer. The article concludes with a review of each disease's surgical history and the ways in which certain procedures produced poor oncologic outcomes.
Collapse
Affiliation(s)
- Hannah Williams
- Division of Colon and Rectal Surgery, Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York
| | - Randolph M. Steinhagen
- Division of Colon and Rectal Surgery, Department of Surgery, The Icahn School of Medicine at Mount Sinai, New York
| |
Collapse
|
|
3
|
Wang MF, Li H, Cui J, Chen YH, Cui Y. Effects of Kalimeris indica (L.) Sch Bip on colitis-associated colorectal cancer. Front Pharmacol 2023; 13:1119091. [PMID: 36699088 PMCID: PMC9868456 DOI: 10.3389/fphar.2022.1119091] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Accepted: 12/28/2022] [Indexed: 01/11/2023] Open
Abstract
Kalimeris indica (L.) Sch Bip (K. indica) is a plant of the genus Kalimeris in Asteraceae, and its whole herb can be used as medicine for the treatment of intestinal inflammatory diseases. But the mechanism is not clear. Therefore, this study was designed to explore the mechanism of K. indica (KI) in colitis-associated colorectal cancer. The expression levels of miR-31-5p and proinflammatory factors were detected using THP-1 and Caco2 cells in vitro. KI could rescue the upregulation of miR-31-5p induced by IL-6 and TNF-α in Caco2 and THP-1 cells. In LPS-stimulated PMA-differentiated THP-1 cells, KI restored miR-31-5p expression by downregulating the expression of IL-6 and TNF-α. C57BL/6 mice were used to construct CAC model through the induction of azoxymethane/dextran sulfate sodium. The successfully established CAC mice were treated with water extract of KI through intragastric administration for 5 weeks. The result showed that KI could significantly reduce the atypical hyperplasia in colon tissue, and inhibit the expression of proinflammatory factors such as IL-6, TNF, IL-11, IL-7, etc. At the same time, KI could restore the level of miR-31-5p in mice, and therefore the downstream LATS2 to inhibit the development of CAC. These above results indicate that KI is a potentially effective herb medicine to prevent CAC.
Collapse
Affiliation(s)
- Mo-Fei Wang
- The Department of General Surgery, The Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia Autonomous Region, China,*Correspondence: Mo-Fei Wang,
| | - Hao Li
- The Department of General Surgery, The Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia Autonomous Region, China
| | - Jian Cui
- The Department of General Surgery, The Affiliated Hospital of Inner Mongolia University for the Nationalities, Tongliao, Inner Mongolia Autonomous Region, China
| | - Yu-Han Chen
- School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang, China
| | - Yong Cui
- School of Medical Device, Shenyang Pharmaceutical University, Shenyang, China
| |
Collapse
|
|
4
|
Al Qudah M, Haboubi N. Pitfalls in the reporting of neoplastic and pseudo neoplastic lesions in the colon and rectum. Folia Med (Plovdiv) 2022; 64:393-400. [PMID: 35856099 DOI: 10.3897/folmed.64.e68357] [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: 05/06/2021] [Accepted: 08/02/2021] [Indexed: 11/12/2022] Open
Abstract
INTRODUCTION Colonic biopsies comprise large portion of pathologists' daily work. Within various pathological entities, there are histological ranges and variations. Unawareness of all of these variabilities might lead to misdiagnosis by an inexperienced pathologist and, accordingly, to mismanagement.
Collapse
Affiliation(s)
| | - Najib Haboubi
- Spire Manchester Hospital, Manchester, United Kingdom
| |
Collapse
|
|
5
|
van der Sloot KWJ, Tiems JL, Visschedijk MC, Festen EAM, van Dullemen HM, Weersma RK, Kats-Ugurlu G, Dijkstra G. Cigarette Smoke Increases Risk for Colorectal Neoplasia in Inflammatory Bowel Disease. Clin Gastroenterol Hepatol 2022; 20:798-805.e1. [PMID: 33453400 DOI: 10.1016/j.cgh.2021.01.015] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/09/2020] [Revised: 12/05/2020] [Accepted: 01/10/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with inflammatory bowel disease are at increased risk of colorectal neoplasia (CRN) due to mucosal inflammation. As current surveillance guidelines form a burden on patients and healthcare costs, stratification of high-risk patients is crucial. Cigarette smoke reduces inflammation in ulcerative colitis (UC) but not Crohn's disease (CD) and forms a known risk factor for CRN in the general population. Due to this divergent association, the effect of smoking on CRN in IBD is unclear and subject of this study. METHODS In this retrospective cohort study, 1,386 IBD patients with previous biopsies analyzed and reported in the PALGA register were screened for development of CRN. Clinical factors and cigarette smoke were evaluated. Patients were stratified for guideline-based risk of CRN. Cox-regression modeling was used to estimate the effect of cigarette smoke and its additive effect within the current risk stratification for prediction of CRN. RESULTS 153 (11.5%) patients developed CRN. Previously described risk factors, i.e. first-degree family member with CRN in CD (p-value=.001), presence of post-inflammatory polyps in UC (p-value=.005), were replicated. Former smoking increased risk of CRN in UC (HR 1.73; 1.05-2.85), whereas passive smoke exposure yielded no effect. For CD, active smoking (2.20; 1.02-4.76) and passive smoke exposure (1.87; 1.09-3.20) significantly increased CRN risk. Addition of smoke exposure to the current risk-stratification model significantly improved model fit for CD. CONCLUSIONS This study is the first to describe the important role of cigarette smoke in CRN development in IBD patients. Adding this risk factor improves the current risk stratification for CRN surveillance strategies.
Collapse
Affiliation(s)
- Kimberley W J van der Sloot
- Department of Gastroenterology and Hepatology, Groningen, the Netherlands; Department of Epidemiology, Groningen, the Netherlands.
| | | | | | - Eleonora A M Festen
- Department of Gastroenterology and Hepatology, Groningen, the Netherlands; Department of Genetics, University of Groningen and University Medical Center Groningen, Groningen, the Netherlands
| | | | - Rinse K Weersma
- Department of Gastroenterology and Hepatology, Groningen, the Netherlands
| | | | - Gerard Dijkstra
- Department of Gastroenterology and Hepatology, Groningen, the Netherlands
| |
Collapse
|
|
6
|
Swoboda J, Mittelsdorf P, Chen Y, Weiskirchen R, Stallhofer J, Schüle S, Gassler N. Intestinal Wnt in the transition from physiology to oncology. World J Clin Oncol 2022; 13:168-185. [PMID: 35433295 PMCID: PMC8966512 DOI: 10.5306/wjco.v13.i3.168] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 09/07/2021] [Accepted: 02/20/2022] [Indexed: 02/06/2023] Open
Abstract
Adult stem cells are necessary for self-renewal tissues and regeneration after damage. Especially in the intestine, which self-renews every few days, they play a key role in tissue homeostasis. Therefore, complex regulatory mechanisms are needed to prevent hyperproliferation, which can lead in the worst case to carcinogenesis or under-activation of stem cells, which can result in dysfunctional epithelial. One main regulatory signaling pathway is the Wnt/β-catenin signaling pathway. It is a highly conserved pathway, with β-catenin, a transcription factor, as target protein. Translocation of β-catenin from cytoplasm to nucleus activates the transcription of numerous genes involved in regulating stem cell pluripo-tency, proliferation, cell differentiation and regulation of cell death. This review presents a brief overview of the Wnt/β-catenin signaling pathway, the regulatory mechanism of this pathway and its role in intestinal homeostasis. Additionally, this review highlights the molecular mechanisms and the histomorphological features of Wnt hyperactivation. Furthermore, the central role of the Wnt signaling pathway in intestinal carcinogenesis as well as its clinical relevance in colorectal carcinoma are discussed.
Collapse
Affiliation(s)
- Julia Swoboda
- Section Pathology, Institute of Forensic Medicine, Jena University Hospital, Jena 07747, Germany
| | - Patrick Mittelsdorf
- Section Pathology, Institute of Forensic Medicine, Jena University Hospital, Jena 07747, Germany
| | - Yuan Chen
- Section Pathology, Institute of Forensic Medicine, Jena University Hospital, Jena 07747, Germany
| | - Ralf Weiskirchen
- Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH University Hospital Aachen, Aachen 52074, Germany
| | - Johannes Stallhofer
- Department of Internal Medicine IV (Gastroenterology, Hepatology, and Infectious Diseases), Jena University Hospital, Jena 07747, Germany
| | - Silke Schüle
- Department of General, Visceral and Vascular Surgery, Jena University Hospital, Jena 07747, Germany
| | - Nikolaus Gassler
- Section Pathology, Institute of Forensic Medicine, Jena University Hospital, Jena 07747, Germany
| |
Collapse
|
|
7
|
Majumder S, Shivaji UN, Kasturi R, Sigamani A, Ghosh S, Iacucci M. Inflammatory bowel disease-related colorectal cancer: Past, present and future perspectives. World J Gastrointest Oncol 2022; 14:547-567. [PMID: 35321275 PMCID: PMC8919014 DOI: 10.4251/wjgo.v14.i3.547] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/21/2021] [Accepted: 02/27/2022] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease-related colorectal cancer (IBD-CRC) is one of the most serious complications of IBD contributing to significant mortality in this cohort of patients. IBD is often associated with diet and lifestyle-related gut microbial dysbiosis, the interaction of genetic and environmental factors, leading to chronic gut inflammation. According to the “common ground hypothesis”, microbial dysbiosis and intestinal barrier impairment are at the core of the chronic inflammatory process associated with IBD-CRC. Among the many underlying factors known to increase the risk of IBD-CRC, perhaps the most important factor is chronic persistent inflammation. The persistent inflammation in the colon results in increased proliferation of cells necessary for repair but this also increases the risk of dysplastic changes due to chromosomal and microsatellite instability. Multiple pathways have been identified, regulated by many positive and negative factors involved in the development of cancer, which in this case follows the ‘inflammation-dysplasia-carcinoma’ sequence. Strategies to lower this risk are extremely important to reduce morbidity and mortality due to IBD-CRC, among which colonoscopic surveillance is the most widely accepted and implemented modality, forming part of many national and international guidelines. However, the effectiveness of surveillance in IBD has been a topic of much debate in recent years for multiple reasons — cost-benefit to health systems, resource requirements, and also because of studies showing conflicting long-term data. Our review provides a comprehensive overview of past, present, and future perspectives of IBD-CRC. We explore and analyse evidence from studies over decades and current best practices followed globally. In the future directions section, we cover emerging novel endoscopic techniques and artificial intelligence that could play an important role in managing the risk of IBD-CRC.
Collapse
Affiliation(s)
- Snehali Majumder
- Department of Clinical Research, Narayana Health, Bangalore 560099, Karnataka, India
| | - Uday Nagesh Shivaji
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, United Kingdom
| | - Rangarajan Kasturi
- Department of Gastroenterology, Narayana Health, Bangalore 560099, India
| | - Alben Sigamani
- Department of Clinical Research, Narayana Health, Bangalore 560099, Karnataka, India
| | - Subrata Ghosh
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, United Kingdom
| | - Marietta Iacucci
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, United Kingdom
| |
Collapse
|
|
8
|
Dougherty MW, Jobin C. Shining a Light on Colibactin Biology. Toxins (Basel) 2021; 13:346. [PMID: 34065799 PMCID: PMC8151066 DOI: 10.3390/toxins13050346] [Citation(s) in RCA: 32] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/06/2021] [Revised: 05/06/2021] [Accepted: 05/10/2021] [Indexed: 12/16/2022] Open
Abstract
Colibactin is a secondary metabolite encoded by the pks gene island identified in several Enterobacteriaceae, including some pathogenic Escherichia coli (E. coli) commonly enriched in mucosal tissue collected from patients with inflammatory bowel disease and colorectal cancer. E. coli harboring this biosynthetic gene cluster cause DNA damage and tumorigenesis in cell lines and pre-clinical models, yet fundamental knowledge regarding colibactin function is lacking. To accurately assess the role of pks+ E. coli in cancer etiology, the biological mechanisms governing production and delivery of colibactin by these bacteria must be elucidated. In this review, we will focus on recent advances in our understanding of colibactin's structural mode-of-action and mutagenic potential with consideration for how this activity may be regulated by physiologic conditions within the intestine.
Collapse
Affiliation(s)
| | - Christian Jobin
- Department of Medicine, University of Florida, Gainesville, FL 32610, USA;
- Department of Infectious Diseases and Inflammation, University of Florida, Gainesville, FL 32610, USA
| |
Collapse
|
|
9
|
Abstract
BACKGROUND Patients undergoing total colectomy for IBD may develop cancer in the rectal remnant, but the association is poorly understood. OBJECTIVES This study aimed to examine the risk and prognosis of rectal cancer after total colectomy for IBD. DESIGN This is a nationwide population-based study. SETTING Treatment of the patients took place in Denmark from 1977 to 2013. PATIENTS Patients with IBD undergoing total colectomy were included. MAIN OUTCOME MEASURES We examined the incidence of rectal cancer among patients with IBD and total colectomy and compared cancer stage to that of other patients with rectal cancer in Denmark. We used Kaplan-Meier methodology to estimate survival and Cox regression to estimate adjusted mortality rate ratios following a rectal cancer diagnosis, comparing patients with and without IBD and a rectal remnant. RESULTS We identified 4703 patients with IBD (1026 Crohn's disease; 3677 ulcerative colitis) who underwent total colectomy with a rectal remnant. During 29,725 years of follow-up, 30 rectal cancers were observed, compared with 8 rectal cancers expected (standardized incidence ratio = 3.6 (95% CI, 2.4-5.1)). Cancer stage distributions were similar. Risk of rectal cancer 35 years after total colectomy was 1.9% (95% CI, 1.1%-2.9%). Five years after rectal cancer diagnosis, survival was 28% (95% CI, 12%-47%) and 38% (95% CI, 37%-38%) for patients with and without IBD and a rectal remnant. The adjusted mortality rate ratio 1 to 5 years after a rectal cancer diagnosis was 2.5 (95% CI, 1.6-3.9). Median time from last recorded nondiagnostic proctoscopy to rectal cancer diagnosis for patients with IBD and total colectomy was 1.1 years. LIMITATIONS This study was limited by the few outcomes and the use of administrative and not clinical data. CONCLUSION Long-term risk of rectal cancer following total colectomy for IBD was low. Survival following a diagnosis of rectal cancer was poorer for patients with IBD and total colectomy than for patients who had rectal cancer without IBD and total colectomy. Endoscopic surveillance, as it appeared to be practiced in this cohort, may be inadequate. See Video Abstract at http://links.lww.com/DCR/B497. RIESGO DE CÁNCER DE RECTO Y SUPERVIVENCIA DESPUÉS DE UNA COLECTOMÍA TOTAL POR ENFERMEDAD INFLAMATORIA INTESTINAL: UN ESTUDIO POBLACIONAL: Los pacientes sometidos a colectomía total por enfermedad inflamatoria intestinal (EII) pueden desarrollar cáncer en el remanente rectal, pero la asociación es poco conocida.Examinar el riesgo y el pronóstico del cáncer de recto después de una colectomía total para la EII.Estudio poblacional a nivel nacional.Dinamarca 1977-2013.Pacientes con EII sometidos a colectomía total.Examinamos la incidencia de cáncer de recto entre pacientes con EII y colectomía total y comparamos el estadio del cáncer con el de otros pacientes con cáncer de recto en Dinamarca. Utilizamos la metodología de Kaplan-Meier para estimar la supervivencia y la regresión de Cox para estimar las tasas de mortalidad ajustadas (aMRR) después de un diagnóstico de cáncer de recto, comparando pacientes con y sin EII y un remanente rectal.Identificamos 4.703 pacientes con EII (1.026 enfermedad de Crohn; 3.677 colitis ulcerosa) que se sometieron a colectomía total con remanente rectal. Durante 29,725 años de seguimiento, se observaron 30 cánceres de recto, en comparación con los 8 esperados [razón de incidencia estandarizada (SIR) = 3.6, (intervalo de confianza (IC) del 95%: 2.4-5.1)]. Las distribuciones de las etapas del cáncer fueron similares. El riesgo de cáncer de recto 35 años después de la colectomía total fue del 1,9% (IC del 95%: 1,1% -2,9%). Cinco años después del diagnóstico de cáncer de recto, la supervivencia fue del 28% (IC del 95%: 12% -47%) y del 38% (IC del 95%: 37% -38%) para los pacientes con y sin EII y un remanente rectal, respectivamente. La aMRR 1-5 años después de un diagnóstico de cáncer de recto fue de 2,5 (IC del 95%: 1,6-3,9). La mediana de tiempo desde la última proctoscopia no diagnóstica registrada hasta el diagnóstico de cáncer de recto en pacientes con EII y colectomía total fue de 1,1 años.Pocos resultados, uso de datos administrativos y no clínicos.El riesgo a largo plazo de cáncer de recto después de una colectomía total para la EII fue bajo. La supervivencia después de un diagnóstico de cáncer de recto fue más pobre para los pacientes con EII y colectomía total que para los pacientes con cáncer de recto sin EII y colectomía total. La vigilancia endoscópica, como parecía practicarse en esta cohorte, puede ser inadecuada. Consulte Video Resumen en http://links.lww.com/DCR/B497. (Traducción-Dr. Adrian Ortega).
Collapse
|
|
10
|
Fantini MC, Guadagni I. From inflammation to colitis-associated colorectal cancer in inflammatory bowel disease: Pathogenesis and impact of current therapies. Dig Liver Dis 2021; 53:558-565. [PMID: 33541800 DOI: 10.1016/j.dld.2021.01.012] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2020] [Revised: 12/23/2020] [Accepted: 01/11/2021] [Indexed: 02/07/2023]
Abstract
The risk of colorectal cancer (CRC) is higher in patients with inflammatory bowel disease (IBD). Population-based data from patients with ulcerative colitis (UC) estimate that the risk of CRC is approximately 2- to 3-fold that of the general population; patients with Crohn's disease appear to have a similar increased risk. However, the true extent of colitis-associated cancer (CAC) in undertreated IBD is unclear. Data suggest that the size (i.e., severity and extent) and persistence of the inflammatory process is largely responsible for the development of CRC in IBD. As patients with IBD and CRC have a worse prognosis than those without a history of IBD, the impact of current therapies for IBD on CAC is of importance. Chronic inflammation of the gut has been shown to increase the risk of developing CAC in both UC and CD. Therefore, control of inflammation is pivotal to the prevention of CAC. This review presents an overview of the current knowledge of CAC in IBD patients, focusing on the role of inflammation in the pathogenesis of CAC and the potential for IBD drugs to interfere with the process of carcinogenesis by reducing the inflammatory process or by modulating pathways directly involved in carcinogenesis.
Collapse
Affiliation(s)
- Massimo Claudio Fantini
- Department of Medical Science and Public Health, Gastroenterology Unit, University of Cagliari, Cittadella Universitaria di Monserrato - Asse Didattico I, SS 554 bivio Sestu, 09042 Monserrato, Cagliari, Italy.
| | | |
Collapse
|
|
11
|
Merli AM, Vieujean S, Massot C, Blétard N, Quesada Calvo F, Baiwir D, Mazzucchelli G, Servais L, Wéra O, Oury C, de Leval L, Sempoux C, Manzini R, Bluemel S, Scharl M, Rogler G, De Pauw E, Coimbra Marques C, Colard A, Vijverman A, Delvenne P, Louis E, Meuwis MA. Solute carrier family 12 member 2 as a proteomic and histological biomarker of dysplasia and neoplasia in ulcerative colitis. J Crohns Colitis 2020; 15:jjaa168. [PMID: 32920643 DOI: 10.1093/ecco-jcc/jjaa168] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Ulcerative colitis (UC) patients have a greater risk of developing colorectal cancer through inflammation-dysplasia-carcinoma sequence of transformation. The histopathological diagnosis of dysplasia is therefore of critical clinical relevance, but dysplasia may be difficult to distinguish from inflammatory changes. METHODS A proteomic pilot study on 5 UC colorectal dysplastic patients highlighted proteins differentially distributed between paired dysplastic, inflammatory and normal tissues. The best candidate marker was selected and immunohistochemistry confirmation was performed on AOM/DSS mouse model lesions, 37 UC dysplasia, 14 UC cancers, 23 longstanding UC, 35 sporadic conventional adenomas, 57 sporadic serrated lesions and 82 sporadic colorectal cancers. RESULTS Differential proteomics found 11 proteins significantly more abundant in dysplasia compared to inflammation, including Solute carrier family 12 member 2 (SLC12A2) which was confidently identified with 8 specific peptides and was below the limit of quantitation in both inflammatory and normal colon. SLC12A2 immunohistochemical analysis confirmed the discrimination of preneoplastic and neoplastic lesions from inflammatory lesions in mice, UC and in sporadic contexts. A specific SLC12A2 staining pattern termed "loss of gradient" reached 89% sensitivity, 95% specificity and 92% accuracy for UC-dysplasia diagnosis together with an inter-observer agreement of 95.24% (multirater κfree of 0.90; IC95%: 0.78 - 1.00). Such discrimination could not be obtained by Ki67 staining. This specific pattern was also associated with sporadic colorectal adenomas and cancers. CONCLUSIONS We found a specific SLC12A2 immunohistochemical staining pattern in precancerous and cancerous colonic UC-lesions which could be helpful for diagnosing dysplasia and cancer in UC and non-UC patients.
Collapse
Affiliation(s)
- Angela-Maria Merli
- Laboratory of Translational Gastroenterology, University of Liège, Liège, Belgium
| | - Sophie Vieujean
- Laboratory of Translational Gastroenterology, University of Liège, Liège, Belgium
- Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium
| | - Charlotte Massot
- Laboratory of Translational Gastroenterology, University of Liège, Liège, Belgium
- Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium
| | - Noella Blétard
- Pathological Anatomy and Cytology, University Hospital CHU of Liège, Liège, Belgium
| | | | | | | | - Laurence Servais
- Laboratory of Cardiology, GIGA-Cardiovascular Sciences, University of Liège, Liège, Belgium
| | - Odile Wéra
- Laboratory of Cardiology, GIGA-Cardiovascular Sciences, University of Liège, Liège, Belgium
| | - Cécile Oury
- Laboratory of Cardiology, GIGA-Cardiovascular Sciences, University of Liège, Liège, Belgium
| | - Laurence de Leval
- Institute of Pathology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Christine Sempoux
- Institute of Pathology, Centre Hospitalier Universitaire Vaudois, University of Lausanne, Lausanne, Switzerland
| | - Roberto Manzini
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Sena Bluemel
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Michael Scharl
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Gerhard Rogler
- Department of Gastroenterology and Hepatology, University Hospital Zurich, University of Zurich, Zurich, Switzerland
| | - Edwin De Pauw
- Laboratory of Mass Spectrometry, University of Liège, Liège, Belgium
| | - C Coimbra Marques
- Abdominal Surgery Department, University Hospital CHU of Liège, Liège, Belgium
| | - Arnaud Colard
- Department of Gastroenterology, CHC Clinique Saint-Joseph, Liège, Belgium
| | - Anne Vijverman
- Department of Gastroenterology, CHR Citadelle, Liège, Belgium
| | - Philippe Delvenne
- Pathological Anatomy and Cytology, University Hospital CHU of Liège, Liège, Belgium
| | - Edouard Louis
- Laboratory of Translational Gastroenterology, University of Liège, Liège, Belgium
- Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium
- Equally contributed to this work
| | - Marie-Alice Meuwis
- Laboratory of Translational Gastroenterology, University of Liège, Liège, Belgium
- Hepato-Gastroenterology and Digestive Oncology, University Hospital CHU of Liège, Liège, Belgium
- Equally contributed to this work
| |
Collapse
|
|
12
|
Sustained Resolution of Multifocal Low-Grade Dysplasia in Ulcerative Colitis. ACG Case Rep J 2019; 6:e00178. [PMID: 31750368 PMCID: PMC6831135 DOI: 10.14309/crj.0000000000000178] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2019] [Accepted: 06/24/2019] [Indexed: 01/27/2023] Open
Abstract
In inflammatory bowel disease, prolonged disease duration, pancolitis, histological inflammation, and subsequent dysplasia are associated with an increased risk for colorectal cancer. Recommendations regarding treatment of low-grade dysplasia (LGD) indicate an individualized approach between colectomy and surveillance. We present a unique case of a patient with ulcerative colitis who had multifocal LGD on 2 consecutive colonoscopies. However, after 10 years and 16 surveillance colonoscopies, she had no further evidence of dysplasia. This appears to be the first case of proven, permanently resolved multifocal LGD in inflammatory bowel disease that challenges our understanding of the natural history of LGD.
Collapse
|