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Al Sulais E, AlAmeel T, Alenzi M, Shehab M, AlMutairdi A, Al-Bawardy B. Colorectal Neoplasia in Inflammatory Bowel Disease. Cancers (Basel) 2025; 17:665. [PMID: 40002259 PMCID: PMC11853504 DOI: 10.3390/cancers17040665] [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: 01/10/2025] [Revised: 02/10/2025] [Accepted: 02/13/2025] [Indexed: 02/27/2025] Open
Abstract
Patients with inflammatory bowel disease (IBD), including ulcerative colitis and colonic Crohn's disease, are at an increased risk of developing colonic dysplasia and neoplasia. Multiple risk factors have been identified that increase the risk of colonic neoplasia in IBD, including but not limited to underlying disease extent, severity, duration, and concomitant primary sclerosing cholangitis. The overall risk of colonic neoplasia in IBD is decreasing but surveillance is still warranted in patients with high-risk features. In this review, we will discuss the epidemiology, pathogenesis, risk factors, approach to surveillance, and management of colonic neoplasia in IBD.
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Affiliation(s)
- Eman Al Sulais
- Department of Medicine, King Fahad Specialist Hospital, Dammam 32253, Saudi Arabia; (E.A.S.)
| | - Turki AlAmeel
- Department of Medicine, King Fahad Specialist Hospital, Dammam 32253, Saudi Arabia; (E.A.S.)
| | - Maram Alenzi
- Department of Medicine, Division of Gastroenterology, Hepatology and Nutrition, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
| | - Mohammad Shehab
- Division of Gastroenterology, Department of Internal Medicine, Mubarak Alkabeer University Hospital, Kuwait University, Aljabreyah 47060, Kuwait
| | - Abdulelah AlMutairdi
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, King Faisal Specialist Hospital and Research Center, Riyadh 11121, Saudi Arabia
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
| | - Badr Al-Bawardy
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, King Faisal Specialist Hospital and Research Center, Riyadh 11121, Saudi Arabia
- College of Medicine, Alfaisal University, Riyadh 11533, Saudi Arabia
- Department of Internal Medicine, Section of Digestive Diseases, Yale School of Medicine, New Haven, CT 06510, USA
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2
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Cao X, Li L, Hu J, Zhu S, Song S, Kong S, Zhou L, Huang Y. Neohesperidin protects against colitis-associated colorectal cancer in mice via suppression of the NF-κB/p65 and MAPK pathways. J Nutr Biochem 2025; 136:109804. [PMID: 39547268 DOI: 10.1016/j.jnutbio.2024.109804] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/11/2024] [Revised: 10/22/2024] [Accepted: 11/07/2024] [Indexed: 11/17/2024]
Abstract
Patients with inflammatory bowel disease (IBD) are at increased risk of developing colitis-associated colorectal cancer (CAC). Neohesperidin (NHP), a flavanone glycoside derived from citrus fruits, has been reported to have anti-inflammatory, antioxidant, and anticancer potential. However, the function of NHP on tumorigenesis has not been well understood. To investigate the potential chemopreventive effects of NHP on CAC development, an in vivo azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model was used and NHP was administered by daily gavage for 10 weeks throughout the model period. In this study, we found that NHP effectively ameliorated AOM/DSS-induced pathological symptoms of colitis and thus inhibited colon tumorigenesis in mice. NHP treatment attenuated tumor proliferation, induced apoptosis, and inhibited angiogenesis during CAC development. In addition, NHP inhibited macrophage infiltration and reduced the expression of proinflammatory cytokines such as TNF-α, IL-1β, IL-6, and COX-2 at both mRNA and protein levels, and the higher the concentration of NHP, the better the inhibition. It is worth noting that the positive therapeutic agent mesalazine (100 mg/kg) had a therapeutic effect comparable to that of a low concentration of NHP (50 mg/kg), but less effective than the same concentration of NHP (100 mg/kg). In addition, NHP may exert anti-inflammatory and anticancer effects by inhibiting the NF-κB/p65 and ERK/p38 MAPK pathways. Our findings highlight the potential of NHP as a potential therapeutic candidate for IBD and CAC.
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Affiliation(s)
- Xingyue Cao
- Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, China
| | - Lingling Li
- Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, China
| | - Jianing Hu
- Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, China
| | - Shuhui Zhu
- Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, China
| | - Shuang Song
- Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, China
| | - Siwei Kong
- Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, China
| | - Li Zhou
- Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, China.
| | - Yefei Huang
- Key Laboratory of Human Genetics and Environmental Medicine, School of Public Health, Xuzhou Medical University, Xuzhou, 221004, China.
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3
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Yamamoto-Furusho JK, Gutierrez-Herrera FD. Molecular Mechanisms and Clinical Aspects of Colitis-Associated Cancer in Ulcerative Colitis. Cells 2025; 14:162. [PMID: 39936954 DOI: 10.3390/cells14030162] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2024] [Revised: 01/14/2025] [Accepted: 01/20/2025] [Indexed: 02/13/2025] Open
Abstract
Inflammatory bowel diseases have long been recognized as entities with a higher risk of colorectal cancer. An increasing amount of information has been published regarding ulcerative colitis-associated colorectal cancer and its unique mechanisms in recent decades, as ulcerative colitis constitutes a chronic process characterized by cycles of activity and remission of unpredictable durations and intensities; cumulative genomic alterations occur during active disease and mucosal healing, resulting in a special sequence of events different to the events associated with sporadic colorectal cancer. The recognition of the core differences between sporadic colorectal cancer and colitis-associated cancer is of great importance to understand and guide the directions in which new research could be performed, and how it could be applied to current clinical scenarios. A DSS/AOM murine model has allowed for a better understanding of the pathogenic mechanisms in colitis-associated cancer, as it is currently the closest model to this unique scenario. In this review, we provide a summary of the main molecular mechanisms and the clinical aspects of colitis-associated cancer in ulcerative colitis.
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Affiliation(s)
- Jesus K Yamamoto-Furusho
- Inflammatory Bowel Disease Clinic, Department of Gastroenterology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Ciudad de México 14080, Mexico
| | - Fausto D Gutierrez-Herrera
- Inflammatory Bowel Disease Clinic, Department of Gastroenterology, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Ciudad de México 14080, Mexico
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4
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Słoka J, Strzałka-Mrozik B, Kubica S, Nowak I, Kruszniewska-Rajs C. Influence of Mesalazine on Ferroptosis-Related Gene Expression in In Vitro Colorectal Cancer Culture. Biomedicines 2025; 13:219. [PMID: 39857803 PMCID: PMC11762154 DOI: 10.3390/biomedicines13010219] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/28/2024] [Revised: 01/13/2025] [Accepted: 01/15/2025] [Indexed: 01/27/2025] Open
Abstract
Background/Objectives: Colorectal cancer (CRC) is one of the most common oncological disorders. Its fundamental treatments include surgery and chemotherapy, predominantly utilizing 5-fluorouracil (5-FU). Despite medical advances, CRC continues to present a high risk of recurrence, metastasis and low survival rates. Consequently, significant emphasis has been directed towards exploring novel types of cell death, particularly ferroptosis. Ferroptosis is characterized by iron imbalance and the accumulation of lipid peroxides and reactive oxygen species (ROS), leading to cellular damage and death. Thus, the discovery of safe inducers of ferroptosis, offering new hope in the struggle against CRC, remains crucial. In this study, we applied the concept of drug repositioning, selecting mesalazine (MES), a non-steroidal anti-inflammatory drug (NSAID), for investigation. Methods: The study was conducted on the colon cancer cell line DLD-1 and normal intestinal epithelial cells from the CCD 841 CoN cell line. Both cell lines were treated with MES solutions at concentrations of 10, 20, 30, 40, and 50 mM. Cytotoxicity was assessed using the MTT assay, while ferroptosis-related gene expression analysis was performed using oligonucleotide microarrays, with RT-qPCR used for validation. Results: MES effectively reduces the viability of DLD-1 cells while minimally affecting normal intestinal cells. Subsequent oligonucleotide microarray analysis revealed that MES significantly alters the expression of 56 genes associated with ferroptosis. Conclusions: Our results suggest that MES may induce ferroptosis in CRC, providing a foundation for further research in this area.
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Affiliation(s)
| | - Barbara Strzałka-Mrozik
- Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland; (J.S.); (S.K.); (I.N.); (C.K.-R.)
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Akyüz F, An YK, Begun J, Aniwan S, Bui HH, Chan W, Choi CH, Chopdat N, Connor SJ, Desai D, Flanagan E, Kobayashi T, Lai AYH, Leong RW, Leow AHR, Leung WK, Limsrivilai J, Muzellina VN, Peddi K, Ran Z, Wei SC, Sollano J, Teo MMH, Wu K, Ye BD, Ooi CJ. Optimizing 5-aminosalicylate for moderate ulcerative colitis: expert recommendations from the Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition. Intest Res 2025; 23:37-55. [PMID: 39492666 PMCID: PMC11834365 DOI: 10.5217/ir.2024.00089] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/18/2024] [Revised: 08/08/2024] [Accepted: 08/09/2024] [Indexed: 11/05/2024] Open
Abstract
The lack of clear definition and classification for "moderate ulcerative colitis (UC)" creates ambiguity regarding the suitability of step-up versus top-down treatment approaches. In this paper, experts address crucial gaps in assessing and managing moderate UC. The Asia-Pacific, Middle East, and Africa Inflammatory Bowel Disease Coalition comprised 24 experts who convened to share, discuss and vote electronically on management recommendations for moderate UC. Experts emphasized that the goal of treating UC is to attain clinical, biomarker, and endoscopic remission using cost-effective strategies such as 5-aminosalicylates (5-ASAs), well-tolerated therapy that can be optimized to improve outcomes. Experts agreed that 5-ASA therapy could be optimized by maximizing dosage (4 g/day for induction of remission), combining oral and topical administration, extending treatment duration beyond 8 weeks, and enhancing patient adherence through personalized counselling and reduced pill burden. Treatment escalation should ideally be reserved for patients with predictors of aggressive disease or those who do not respond to 5-ASA optimization. Premature treatment escalation to advanced therapies (including biologics and oral small molecules) may have long-term health and financial consequences. This paper provides consensus-based expert recommendations and a treatment algorithm, based on current evidence and practices, to assist decision-making in real-world settings.
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Affiliation(s)
- Filiz Akyüz
- Department of Gastroenterology, Istanbul Faculty of Medicine, Istanbul University, Istanbul, Türkiye
| | - Yoon Kyo An
- Department of Gastroenterology, Mater Hospital Brisbane, Brisbane, Australia
| | - Jakob Begun
- Department of Gastroenterology, Mater Hospital Brisbane, Brisbane, Australia
| | - Satimai Aniwan
- Division of Gastroenterology, King Chulalongkorn Memorial Hospital, Chulalongkorn University, Bangkok, Thailand
| | - Huu Hoang Bui
- Department of Gastroenterology, University Medical Center, University of Medicine and Pharmacy at Ho Chi Minh City, Ho Chi Minh City, Vietnam
| | - Webber Chan
- The Gastroenterology Group, Gleneagles Hospital, Singapore
| | - Chang Hwan Choi
- Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Korea
| | - Nazeer Chopdat
- Department of Gastroenterology, Baragwanath Hospital, University of the Witwatersrand, Johannesburg, South Africa
| | - Susan J Connor
- Department of Gastroenterology, Liverpool Hospital, Sydney, Australia
- South Western Clinical School, University of New South Wales, Sydney, Australia
| | - Devendra Desai
- Division of Medical Gastroenterology, P. D. Hinduja Hospital, Mumbai, India
| | - Emma Flanagan
- Department of Gastroenterology, St. Vincent’s Hospital, Melbourne, Australia
| | - Taku Kobayashi
- Center for Advanced IBD Research and Treatment, Kitasato University Kitasato Institute Hospital, Tokyo, Japan
| | - Allen Yu-Hung Lai
- Global Health Program, College of Public Health, National Taiwan University, Taipei, Taiwan
- Ferring Pharmaceuticals, Singapore
| | - Rupert W Leong
- Department of Gastroenterology, Concord Hospital, Sydney, Australia
| | | | - Wai Keung Leung
- Department of Medicine, University of Hong Kong, Hong Kong, China
| | - Julajak Limsrivilai
- Deparment of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand
| | - Virly Nanda Muzellina
- Gastrointestinal Endoscopy Center, Cipto Mangunkusumo General Hospital, Jakarta, Indonesia
- Universitas Indonesia, Jakarta, Indonesia
| | - Kiran Peddi
- Department of Gastroenterology, Yashoda Hospital, Hyderabad, India
| | - Zhihua Ran
- Department of Gastroenterology, Zhoupu Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Shu Chen Wei
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jose Sollano
- Faculty of Medicine and Surgery, University of Santo Tomas, Manila, Philippines
| | | | - Kaichun Wu
- Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, China
| | - Byong Duk Ye
- Department of Gastroenterology and Inflammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea
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Abdu-Allah HHM, El-Nagar MKS, Qayed WS, Salem OIA, Kafafy AHN, El-Awady R, Nicola MA. N-Substituted-5- [(2,5-Dihydroxybenzyl)amino]salicylamides as Lavendustin Analogs: Antiproliferative Activity, COMPARE Analyses, Mechanistic, Docking, ADMET and Toxicity Studies. Chem Biol Drug Des 2025; 105:e70052. [PMID: 39865457 DOI: 10.1111/cbdd.70052] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/21/2024] [Revised: 11/26/2024] [Accepted: 01/07/2025] [Indexed: 01/28/2025]
Abstract
Target cyclooxygenase 2 (COX-2) and 5-lipoxygenase (5-LOX) inhibitors; 5-([2,5-Dihydroxybenzyl]amino)salicylamides (Compounds 1-11) were examined for potential anticancer activity, with a trial to assess the underlying possible mechanisms. Compounds were assessed at a single dose against 60 cancer cell lines panel and those with the highest activity were tested in the five-dose assay. COMPARE analysis was conducted to explore potential mechanisms underlying their biological activity. In vitro epidermal growth factor receptor (EGFR) inhibitory activity was performed, as well as cell cycle and apoptosis assays, in addition to molecular docking to rationalize the potential of these compounds as potent EGFR inhibitors. The compounds revealed broad-spectrum anticancer activity against most cancer cell lines, particularly those of leukemia. Compound 9 showed the maximum growth inhibition (99.65%) against leukemia HL-60 (TB) cell line. Compound 5 produced the uppermost cytotoxic activity (62.28%) against non-small cell lung cancer cell line (NCI-H522), and the most potent antiproliferative and cytotoxic activities against the same cell line in the five-dose assay. Flow cytometry of cell cycle distribution on NCI-H522 showed arrest of cells at different phases of the cycle by Compounds 4, 5, 9-11. These compounds induced apoptosis in NCI-H522, particularly Compounds 4 and 5. They showed a remarkable in vitro EGFR inhibitory activity that was comparable to erlotinib, and a predicted ADME pharmacokinetic profile. In conclusion, the N-substituted aminosalicylamides exhibited considerable anticancer activity. The pattern of N-substitution is important in their activity. The compounds exhibited polypharmacology; one of the targets is the EGFR, as supported by molecular docking.
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Affiliation(s)
- Hajjaj H M Abdu-Allah
- Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt
| | - Mohamed K S El-Nagar
- Pharmaceutical Chemistry Department, Faculty of Pharmacy, University of Sadat City, Egypt
| | - Wesam S Qayed
- Medicinal Chemistry Department, Faculty of Pharmacy, Assiut University, Assiut, Egypt
| | - Ola I A Salem
- Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt
| | - Abdel-Hamid N Kafafy
- Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Assiut University, Assiut, Egypt
| | - Raafat El-Awady
- Sharjah Institute for Medical Research and College of Pharmacy, University of Sharjah, Sharjah, UAE
| | - Mariam A Nicola
- Department of Pharmacology and Toxicology, Faculty of Pharmacy, Assiut University, Assiut, Egypt
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Rivera Antonio A, Padilla Martínez I, Márquez-Flores Y, Juárez Solano A, Torres Ramos M, Rosales Hernández M. Protective effect of (E)-(2,4-dihydroxy)-α-aminocinnamic acid, a hydroxy cinnamic acid derivative, in an ulcerative colitis model induced by TNBS. Biosci Rep 2024; 44:BSR20240797. [PMID: 39268608 PMCID: PMC11461179 DOI: 10.1042/bsr20240797] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2024] [Revised: 09/02/2024] [Accepted: 09/10/2024] [Indexed: 09/17/2024] Open
Abstract
Ulcerative colitis (UC) is a multifactorial disease that causes long-lasting inflammation and ulcers in the digestive tract. UC is the most common form of inflammatory bowel disease (IBD). The current treatment for mild-to-moderate UC involves the use of 5-aminosalicylates (5-ASA), but much of this compound is unabsorbed and metabolized by N-acetylation. Several efforts have since been made to evaluate new molecules from synthetic or natural sources. Recently, it was reported that (E)-(5-chloro-2-hydroxy)-α-aminocinnamic acid (2c) and (E)-(2,4-dihydroxy)-α-aminocinnamic acid (2f) are as good or better myeloperoxidase (MPO) inhibitors and antioxidants than 5-ASA. Then, the present study aimed to evaluate the protective effects of 2c and 2f on a rat model of UC induced by 2,4,6-trinitrobenzene sulfonic acid (TNBS). The results showed that TNBS caused the induction of colonic ulcers, as well as a significant increase in MPO activity and malondialdehyde (MDA) and a decrease in glutathione (GSH) content. The administration of 2f, 2c and 5-ASA, decreased the ulcers presence, inhibited MPO peroxidation activity and MPO presence (as determined by immunofluorescence), and increased GSH and reduced MDA content. However, 2f was better than 2c and 5-ASA, then, the principal mechanism by which 2f presented a protective effect in a UC model induced by TNBS in rats is by inhibiting MPO activity and due to its antioxidant activity.
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Affiliation(s)
- Astrid Mayleth Rivera Antonio
- Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomas, Ciudad de México 11340, México
| | - Itzia Irene Padilla Martínez
- Laboratorio de Química Supramolecular y Nanociencias, Unidad Profesional Interdisciplinaria de Biotecnología, Instituto Politécnico Nacional, Avenida Acueducto s/n, Barrio la Laguna Ticomán, Ciudad de México 07340, México
| | - Yazmín Karina Márquez-Flores
- Departamento de Farmacia, Escuela Nacional de Ciencias Biológicas, Campus Zacatenco, Instituto Politécnico Nacional, Av. Wilfrido Massieu s/n Col. Zacatenco, C.P. 07738, Ciudad de México, México
| | - Alan Hipólito Juárez Solano
- Dirección de investigación del Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez. Av. Insurgentes sur #3877, col. La Fama. Tlalpan, Ciudad de México. C.P. 14269. México
| | - Mónica A. Torres Ramos
- Dirección de investigación del Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez. Av. Insurgentes sur #3877, col. La Fama. Tlalpan, Ciudad de México. C.P. 14269. México
| | - Martha Cecilia Rosales Hernández
- Laboratorio de Biofísica y Biocatálisis, Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Plan de San Luis y Salvador Díaz Mirón s/n, Casco de Santo Tomas, Ciudad de México 11340, México
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Fanizza J, Bencardino S, Allocca M, Furfaro F, Zilli A, Parigi TL, Fiorino G, Peyrin-Biroulet L, Danese S, D'Amico F. Inflammatory Bowel Disease and Colorectal Cancer. Cancers (Basel) 2024; 16:2943. [PMID: 39272800 PMCID: PMC11394070 DOI: 10.3390/cancers16172943] [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: 07/29/2024] [Revised: 08/21/2024] [Accepted: 08/22/2024] [Indexed: 09/15/2024] Open
Abstract
Patients with inflammatory bowel diseases (IBDs), including both ulcerative colitis (UC) and Crohn's disease (CD), are at a higher risk of developing colorectal cancer (CRC). However, advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have led to a decrease in the incidence of CRC among IBD patients. Currently, the management of patients with IBD who have a history of or ongoing active malignancy is an unmet need. This involves balancing the risk of cancer recurrence/progression with the potential exacerbation of IBD if the medications are discontinued. The objective of this review is to provide an updated summary of the epidemiology, causes, risk factors, and surveillance approaches for CRC in individuals with IBD, and to offer practical guidance on managing IBD patients with history of previous or active cancer.
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Affiliation(s)
- Jacopo Fanizza
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Sarah Bencardino
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Mariangela Allocca
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Federica Furfaro
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Alessandra Zilli
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Tommaso Lorenzo Parigi
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Gionata Fiorino
- IBD Unit, Department of Gastroenterology and Digestive Endoscopy, San Camillo-Forlanini Hospital, 00152 Rome, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- INSERM, NGERE, University of Lorraine, F-54000 Nancy, France
- INFINY Institute, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- FHU-CURE, Nancy University Hospital, F-54500 Vandœuvre-lès-Nancy, France
- Groupe Hospitalier Privè Ambroise Parè-Hartmann, Paris IBD Center, 92200 Neuilly sur Seine, France
- Division of Gastroenterology and Hepatology, McGill University Health Center, Montreal, QC H4A 3J1, Canada
| | - Silvio Danese
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
| | - Ferdinando D'Amico
- Department of Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital and Vita-Salute San Raffaele University, 20132 Milan, Italy
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9
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Adamowicz M, Abramczyk J, Kilanczyk E, Milkiewicz P, Łaba A, Milkiewicz M, Kempinska-Podhorodecka A. Modulation of miR-155-5p signalling via 5-ASA for the prevention of high microsatellite instability: an in vitro study using human epithelial cell lines. J Physiol Biochem 2024; 80:573-583. [PMID: 38985369 PMCID: PMC11502576 DOI: 10.1007/s13105-024-01033-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2024] [Accepted: 06/28/2024] [Indexed: 07/11/2024]
Abstract
5-aminosalicylic acid (5-ASA) is a first-line treatment for maintaining colitis remission. It is a highly effective, safe, and well-tolerated drug with anti-inflammatory and chemo-preventive properties. While patients with primary sclerosing cholangitis (PSC) with concomitant ulcerative colitis are treated with 5-ASA, the molecular mechanisms underlying the drug's chemo-preventive effects are not entirely understood. We previously reported that bile acids and lipopolysaccharide-induced miR-155 expression was associated with downregulating mismatch repair (MMR) proteins in CACO-2 cell lines. Therefore, in this investigation, a set of in vitro functional studies was performed to show the possible mechanisms behind the epigenetic relationship between miR-155 and 5-ASA's prevention of high microsatellite instability (MSI-H). In transient transfection with miR-155Mimic, which behaves like endogenous miRNA, we confirmed the relationships between miR-155 and its target MMR in three human intestinal epithelial cell lines: CACO-2, NCM460D and HT-29. We have shown, for the first time, that 5-ASA modulates MLH1, MSH2, MSH6 in miR-155 transfected cells. These findings underline that chemoprotective 5-ASA therapy can effectively attenuate the expression of miR-155 and potentially prevent a development of MSI-H in a subset of colorectal cancers associated with PSC.
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Affiliation(s)
- Monika Adamowicz
- Department of Medical Biology, Pomeranian Medical University in Szczecin, Szczecin, 70-111, Poland
| | - Joanna Abramczyk
- Department of Medical Biology, Pomeranian Medical University in Szczecin, Szczecin, 70-111, Poland
| | - Ewa Kilanczyk
- Department of Medical Biology, Pomeranian Medical University in Szczecin, Szczecin, 70-111, Poland
| | - Piotr Milkiewicz
- Liver and Internal Medicine Unit, Medical University of Warsaw, Warszawa, Poland
- Translational Medicine Group, Pomeranian Medical University in Szczecin, Szczecin, Poland
| | - Alicja Łaba
- Department of Medical Biology, Pomeranian Medical University in Szczecin, Szczecin, 70-111, Poland
| | - Malgorzata Milkiewicz
- Department of Medical Biology, Pomeranian Medical University in Szczecin, Szczecin, 70-111, Poland
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10
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Rais T, Riaz R, Siddiqui T, Shakeel A, Khan A, Zafar H. Innovations in colorectal cancer treatment: trifluridine and tipiracil with bevacizumab for improved outcomes - a review. Front Oncol 2024; 14:1296765. [PMID: 39070141 PMCID: PMC11272516 DOI: 10.3389/fonc.2024.1296765] [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: 10/06/2023] [Accepted: 06/14/2024] [Indexed: 07/30/2024] Open
Abstract
Colorectal cancer ranks second in cancer-related deaths throughout the world. At the time of diagnosis, at least 20% of the patients with CRC had already developed metastases. Treating and effectively managing metastatic colorectal cancer remains an unsolved task for the health sector. Research and clinical trials have been done to find the best possible solution for patients diagnosed with metastatic colorectal cancer. The approval of the combination therapy of trifluridine and tipiracil with bevacizumab for previously treated metastatic colorectal cancer (CRC) by the Food and Drug Administration (FDA) is a remarkable breakthrough in CRC treatment. Our goal through this article is to give detailed knowledge about the pathogenesis of CRC, its prevalence, and its clinical features. Here, we have also discussed the past medical treatments that have been used for treating mCRC, including the anti-EGFR therapy, aflibercept, ramucirumab, and regorafenib. However, the focus of this document is to assess the combination of LONSURF (trifluridine/tipiracil) and bevacizumab by reviewing the clinical trials and relevant research.
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Affiliation(s)
- Taruba Rais
- Internal Medicine, Dow University of Health Sciences (DUHS), Karachi, Pakistan
| | - Rumaisa Riaz
- Internal Medicine, Dow University of Health Sciences (DUHS), Karachi, Pakistan
| | - Tasmiyah Siddiqui
- Internal Medicine, Dow University of Health Sciences (DUHS), Karachi, Pakistan
| | - Amna Shakeel
- Internal Medicine, Dow University of Health Sciences (DUHS), Karachi, Pakistan
| | - Afsheen Khan
- Internal Medicine, Dow University of Health Sciences (DUHS), Karachi, Pakistan
| | - Habiba Zafar
- Internal Medicine, Jinnah Sindh Medical University (JSMU), Karachi, Pakistan
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11
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Liu M, Zhong XS, Krishnachaitanya SS, Ou R, Dashwood RH, Powell DW, Li Q. Erlotinib suppresses tumorigenesis in a mouse model of colitis-associated cancer. Biomed Pharmacother 2024; 175:116580. [PMID: 38723513 PMCID: PMC11883833 DOI: 10.1016/j.biopha.2024.116580] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/08/2024] [Revised: 03/28/2024] [Accepted: 04/10/2024] [Indexed: 06/03/2024] Open
Abstract
Colitis-associated cancer (CAC) in inflammatory bowel diseases exhibits more aggressive behavior than sporadic colorectal cancer; however, the molecular mechanisms remain unclear. No definitive preventative agent against CAC is currently established in the clinical setting. We investigated the molecular mechanisms of CAC in the azoxymethane/dextran sulfate sodium (AOM/DSS) mouse model and assessed the antitumor efficacy of erlotinib, a small molecule inhibitor of the epidermal growth factor receptor (EGFR). Erlotinib premixed with AIN-93 G diet at 70 or 140 parts per million (ppm) inhibited tumor multiplicity significantly by 96%, with ∼60% of the treated mice exhibiting zero polyps at 12 weeks. Bulk RNA-sequencing revealed more than a thousand significant gene alterations in the colons of AOM/DSS-treated mice, with KEGG enrichment analysis highlighting 46 signaling pathways in CAC development. Erlotinib altered several signaling pathways and rescued 40 key genes dysregulated in CAC, including those involved in the Hippo and Wnt signaling. These findings suggest that the clinically-used antitumor agent erlotinib might be repurposed for suppression of CAC, and that further studies are warranted on the crosstalk between dysregulated Wnt and EGFR signaling in the corresponding patient population.
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Affiliation(s)
- Max Liu
- Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, TX, USA
| | - Xiaoying S Zhong
- Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, TX, USA
| | - Srikruthi S Krishnachaitanya
- Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, TX, USA
| | - Rongliwen Ou
- Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, TX, USA; Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, China
| | - Roderick H Dashwood
- Center for Epigenetics & Disease Prevention, Texas A&M School of Medicine, Houston, TX, USA
| | - Don W Powell
- Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, TX, USA
| | - Qingjie Li
- Division of Gastroenterology, Department of Internal Medicine, University of Texas Medical Branch at Galveston, Galveston, TX, USA.
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12
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Walsh M, Rahman S, Gologorsky R, Tsikitis VL. Colorectal Neoplasia in the Setting of Inflammatory Bowel Disease. Surg Clin North Am 2024; 104:673-684. [PMID: 38677829 DOI: 10.1016/j.suc.2023.12.006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 04/29/2024]
Abstract
Inflammatory bowel disease (IBD) is associated with an increased risk of colorectal cancer (colorectal adenocarcinoma [CRC]) compared with the general population. IBD-related CRC is related to poorer outcomes than non-IBD-related CRC, and it accounts for 10% to 15% of death in patients with IBD. As such, screening guidelines have been made specific to this population recommending shorter intervals of endoscopic screening to detect dysplasia and CRC relative to the general population. Advances in endoscopic technology allow for improved visualization of dysplasia, which has led to widespread adoption of dye-spray chromoendoscopy with targeted biopsy.
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Affiliation(s)
- Maura Walsh
- Department of General Surgery, Oregon Health Sciences University, 3181 Southwest Sam Jackson Park Road L-579, Portland, OR 97239, USA.
| | - Shahrose Rahman
- Department of Surgery, Oregon Health Sciences University, 3181 Southwest Sam Jackson Park Road L-579, Portland, OR 97239, USA
| | - Rebecca Gologorsky
- Oregon Health Sciences University, 3181 Southwest Sam Jackson Park Road L-579, Portland, OR 97239, USA
| | - Vassiliki Liana Tsikitis
- Department of Surgery, Oregon Health Sciences University, 3181 Southwest Sam Jackson Park Road L-579, Portland, OR 97239, USA
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13
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Ogurchenok NE, Khalin KD, Bryukhovetskiy IS. Chemoprophylaxis of precancerous lesions in patients who are at a high risk of developing colorectal cancer (Review). MEDICINE INTERNATIONAL 2024; 4:25. [PMID: 38628384 PMCID: PMC11019464 DOI: 10.3892/mi.2024.149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/05/2023] [Accepted: 03/07/2024] [Indexed: 04/19/2024]
Abstract
The diagnostics of colorectal cancer (CRC) and precancerous lesions in the colon is one of the most urgent matters to be considered for the modern protocols of complex examination, recommended for use from the age of 45 years, and including both instrumental and laboratory methods of research: Colonoscopy, CT colonography, flexible sigmoidoscopy, fecal occult blood test, fecal immunohistochemistry test and stool DNA test Nevertheless, the removal of those precancerous lesions does not solve the issue, and, apart from the regular endoscopic monitoring of patients who are at a high risk of developing CRC, the pharmacological treatment of certain key pathogenic mechanisms leading to the development of CRC is required. The present review to discusses the function of β-catenin in the transformation of precancerous colorectal lesions into CRC, when collaborating with PI3K/AKT/mTOR signaling pathway and other mechanisms. The existing methods for the early diagnostics and prevention of discovered anomalies are described and categorized. The analysis of the approaches to chemoprophylaxis of CRC, depending on the results of endoscopic, morphological and molecular-genetic tests, is presented.
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Affiliation(s)
- Nonna E. Ogurchenok
- Far Eastern Federal University, School of Medicine and Life Sciences, FEFU Medical Center, Russky Island, 690091 Vladivostok, Russian Federation
- Primorskiy Regional Clinical Hospital N1, Medical Center, Russky Island, 690091 Vladivostok, Russian Federation
| | - Konstantin D. Khalin
- Far Eastern Federal University, School of Medicine and Life Sciences, FEFU Medical Center, Russky Island, 690091 Vladivostok, Russian Federation
- Far Eastern Federal University, Medical Center, Russky Island, 690091 Vladivostok, Russian Federation
| | - Igor S. Bryukhovetskiy
- Far Eastern Federal University, Medical Center, Russky Island, 690091 Vladivostok, Russian Federation
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14
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Meštrović A, Kumric M, Bozic J. Discontinuation of therapy in inflammatory bowel disease: Current views. World J Clin Cases 2024; 12:1718-1727. [PMID: 38660068 PMCID: PMC11036474 DOI: 10.12998/wjcc.v12.i10.1718] [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: 12/31/2023] [Revised: 02/25/2024] [Accepted: 03/14/2024] [Indexed: 04/02/2024] Open
Abstract
The timely introduction and adjustment of the appropriate drug in accordance with previously well-defined treatment goals is the foundation of the approach in the treatment of inflammatory bowel disease (IBD). The therapeutic approach is still evolving in terms of the mechanism of action but also in terms of the possibility of maintaining remission. In patients with achieved long-term remission, the question of de-escalation or discontinuation of therapy arises, considering the possible side effects and economic burden of long-term therapy. For each of the drugs used in IBD (5-aminosalycaltes, immunomodulators, biological drugs, small molecules) there is a risk of relapse. Furthermore, studies show that more than 50% of patients who discontinue therapy will relapse. Based on the findings of large studies and meta-analysis, relapse of disease can be expected in about half of the patients after therapy withdrawal, in case of monotherapy with aminosalicylates, immunomodulators or biological therapy. However, longer relapse-free periods are recorded with withdrawal of medication in patients who had previously been on combination therapies immunomodulators and anti-tumor necrosis factor. It needs to be stressed that randomised clinical trials regarding withdrawal from medications are still lacking. Before making a decision on discontinuation of therapy, it is important to distinguish potential candidates and predictive factors for the possibility of disease relapse. Fecal calprotectin level has currently been identified as the strongest predictive factor for relapse. Several other predictive factors have also been identified, such as: High Crohn's disease activity index or Harvey Bradshaw index, younger age (< 40 years), longer disease duration (> 40 years), smoking, young age of disease onset, steroid use 6-12 months before cessation. An important factor in the decision to withdraw medication is the success of re-treatment with the same or other drugs. The decision to discontinue therapy must be based on individual approach, taking into account the severity, extension, and duration of the disease, the possibility of side adverse effects, the risk of relapse, and patient's preferences.
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Affiliation(s)
- Antonio Meštrović
- Department of Gastroenterology, University Hospital of Split, Split 21000, Croatia
| | - Marko Kumric
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
| | - Josko Bozic
- Department of Pathophysiology, University of Split School of Medicine, Split 21000, Croatia
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15
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Hajjar R, Oliero M, Fragoso G, Ajayi AS, Alaoui AA, Vennin Rendos H, Calvé A, Cuisiniere T, Gerkins C, Thérien S, Taleb N, Dagbert F, Sebajang H, Loungnarath R, Schwenter F, Ratelle R, Wassef R, De Broux E, Richard C, Santos MM. Modulating Gut Microbiota Prevents Anastomotic Leak to Reduce Local Implantation and Dissemination of Colorectal Cancer Cells after Surgery. Clin Cancer Res 2024; 30:616-628. [PMID: 38010363 DOI: 10.1158/1078-0432.ccr-23-1601] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/28/2023] [Revised: 08/10/2023] [Accepted: 11/21/2023] [Indexed: 11/29/2023]
Abstract
PURPOSE Anastomotic leak (AL) is a major complication in colorectal cancer surgery and consists of the leakage of intestinal content through a poorly healed colonic wound. Colorectal cancer recurrence after surgery is a major determinant of survival. We hypothesize that AL may allow cancer cells to escape the gut and lead to cancer recurrence and that improving anastomotic healing may prevent local implantation and metastatic dissemination of cancer cells. EXPERIMENTAL DESIGN We investigated the association between AL and postoperative outcomes in patients with colorectal cancer. Using mouse models of poor anastomotic healing, we assessed the processes of local implantation and dissemination of cancer cells. The effect of dietary supplementation with inulin and 5-aminosalicylate (5-ASA), which activate PPAR-γ in the gut, on local anastomotic tumors was assessed in mice undergoing colonic surgery. Inulin and 5-ASA were also assessed in a mouse model of liver metastasis. RESULTS Patients experiencing AL displayed lower overall and oncologic survival than non-AL patients. Poor anastomotic healing in mice led to larger anastomotic and peritoneal tumors. The microbiota of patients with AL displays a lower capacity to activate the antineoplastic PPAR-γ in the gut. Modulation of gut microbiota using dietary inulin and 5-ASA reinforced the gut barrier and prevented anastomotic tumors and metastatic spread in mice. CONCLUSIONS Our findings reinforce the hypothesis that preventing AL is paramount to improving oncologic outcomes after colorectal cancer surgery. Furthermore, they pave the way toward dietary targeting of PPAR-γ as a novel way to enhance healing and diminish cancer recurrence.
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Affiliation(s)
- Roy Hajjar
- Nutrition and Microbiome Laboratory, Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada
- Digestive Surgery Service, Department of Surgery, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada
- Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Canada
| | - Manon Oliero
- Nutrition and Microbiome Laboratory, Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada
| | - Gabriela Fragoso
- Nutrition and Microbiome Laboratory, Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada
| | - Ayodeji Samuel Ajayi
- Nutrition and Microbiome Laboratory, Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada
| | - Ahmed Amine Alaoui
- Nutrition and Microbiome Laboratory, Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada
- Digestive Surgery Service, Department of Surgery, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada
- Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Canada
| | - Hervé Vennin Rendos
- Nutrition and Microbiome Laboratory, Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada
| | - Annie Calvé
- Nutrition and Microbiome Laboratory, Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada
| | - Thibault Cuisiniere
- Nutrition and Microbiome Laboratory, Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada
| | - Claire Gerkins
- Nutrition and Microbiome Laboratory, Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada
| | - Sophie Thérien
- Digestive Surgery Service, Department of Surgery, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada
| | - Nassima Taleb
- Digestive Surgery Service, Department of Surgery, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada
| | - François Dagbert
- Digestive Surgery Service, Department of Surgery, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada
- Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Canada
| | - Herawaty Sebajang
- Digestive Surgery Service, Department of Surgery, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada
- Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Canada
| | - Rasmy Loungnarath
- Digestive Surgery Service, Department of Surgery, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada
- Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Canada
| | - Frank Schwenter
- Digestive Surgery Service, Department of Surgery, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada
- Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Canada
| | - Richard Ratelle
- Digestive Surgery Service, Department of Surgery, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada
- Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Canada
| | - Ramses Wassef
- Digestive Surgery Service, Department of Surgery, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada
- Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Canada
| | - Eric De Broux
- Digestive Surgery Service, Department of Surgery, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada
- Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Canada
| | - Carole Richard
- Digestive Surgery Service, Department of Surgery, Centre hospitalier de l'Université de Montréal (CHUM), Montréal, Canada
- Department of Surgery, Faculty of Medicine, Université de Montréal, Montréal, Canada
| | - Manuela M Santos
- Nutrition and Microbiome Laboratory, Institut du cancer de Montréal and Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montréal, Canada
- Department of Medicine, Faculty of Medicine, Université de Montréal, Montréal, Canada
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16
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Zhang H, Shi Y, Lin C, He C, Wang S, Li Q, Sun Y, Li M. Overcoming cancer risk in inflammatory bowel disease: new insights into preventive strategies and pathogenesis mechanisms including interactions of immune cells, cancer signaling pathways, and gut microbiota. Front Immunol 2024; 14:1338918. [PMID: 38288125 PMCID: PMC10822953 DOI: 10.3389/fimmu.2023.1338918] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 12/26/2023] [Indexed: 01/31/2024] Open
Abstract
Inflammatory bowel disease (IBD), characterized primarily by gastrointestinal inflammation, predominantly manifests as Crohn's disease (CD) and ulcerative colitis (UC). It is acknowledged that Inflammation plays a significant role in cancer development and patients with IBD have an increased risk of various cancers. The progression from inflammation to carcinogenesis in IBD is a result of the interplay between immune cells, gut microbiota, and carcinogenic signaling pathways in epithelial cells. Long-term chronic inflammation can lead to the accumulation of mutations in epithelial cells and the abnormal activation of carcinogenic signaling pathways. Furthermore, Immune cells play a pivotal role in both the acute and chronic phases of IBD, contributing to the transformation from inflammation to tumorigenesis. And patients with IBD frequently exhibit dysbiosis of the intestinal microbiome. Disruption of the gut microbiota and subsequent immune dysregulation are central to the pathogenesis of both IBD and colitis associated colorectal cancer (CAC). The proactive management of inflammation combined with regular endoscopic and tumor screenings represents the most direct and effective strategy to prevent the IBD-associated cancer.
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Affiliation(s)
- Haonan Zhang
- Inflammatory Bowel Diseases Research Center, Department of Gastroenterology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Yulu Shi
- Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Chanchan Lin
- Department of Gastroenterology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou, Fujian, China
| | - Chengcheng He
- Inflammatory Bowel Diseases Research Center, Department of Gastroenterology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Shanping Wang
- Inflammatory Bowel Diseases Research Center, Department of Gastroenterology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Qingyuan Li
- Guangdong Provincial Key Laboratory of Gastroenterology, Department of Gastroenterology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
| | - Yan Sun
- Inflammatory Bowel Diseases Research Center, Department of Gastroenterology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
| | - Mingsong Li
- Inflammatory Bowel Diseases Research Center, Department of Gastroenterology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, China
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17
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Ozawa N, Yokobori T, Osone K, Bilguun EO, Okami H, Shimoda Y, Shiraishi T, Okada T, Sano A, Sakai M, Sohda M, Miyazaki T, Ide M, Ogawa H, Yao T, Oyama T, Shirabe K, Saeki H. MAdCAM-1 targeting strategy can prevent colitic cancer carcinogenesis and progression via suppression of immune cell infiltration and inflammatory signals. Int J Cancer 2024; 154:359-371. [PMID: 37676657 DOI: 10.1002/ijc.34722] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2023] [Revised: 05/19/2023] [Accepted: 06/13/2023] [Indexed: 09/08/2023]
Abstract
Chronic inflammation caused by infiltrating immune cells can promote colitis-associated dysplasia/colitic cancer in ulcerative colitis (UC) by activating inflammatory cytokine signalling through the IL-6/p-STAT3 and TNFα/NF-κB pathways. Mucosal addressin cell adhesion molecule-1 (MAdCAM-1) expressed on high endothelial venules promotes the migration of immune cells from the bloodstream to the gut via interaction with α4β7 integrin expressed on the immune cells. MAdCAM-1, has therefore drawn interest as a novel therapeutic target for treating active UC. However, the role of MAdCAM-1-positive endothelial cells in immune cell infiltration in dysplasia/colitic cancers remains unclear. We evaluated the expression of MAdCAM-1, CD31 and immune cell markers (CD8, CD68, CD163 and FOXP3) in samples surgically resected from 11 UC patients with dysplasia/colitic cancer and 17 patients with sporadic colorectal cancer (SCRC), using immunohistochemical staining. We used an azoxymethane/dextran sodium sulphate mouse model (AOM/DSS mouse) to evaluate whether dysplasia/colitic cancer could be suppressed with an anti-MAdCAM-1 blocking antibody by preventing immune cell infiltration. The number of MAdCAM-1-positive vessels and infiltrating CD8+ , CD68+ and CD163+ immune cells was significantly higher in dysplasia/colitic cancer than in normal, SCRC and UC mucosa. In AOM/DSS mice, the anti-MAdCAM-1 antibody reduced the number, mean diameter, depth of tumours, Ki67 positivity, number of CD8+ , CD68+ and CD163+ immune cells and the IL-6/p-STAT3 and TNF-α/NF-κB signalling. Our results indicate that targeting MAdCAM-1 is a promising strategy for controlling not only UC severity but also carcinogenesis and tumour progression by regulating inflammation/immune cell infiltration in patients with UC.
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Affiliation(s)
- Naoya Ozawa
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
| | - Takehiko Yokobori
- Division of Integrated Oncology Research, Gunma University, Initiative for Advanced Research (GIAR), Maebashi, Gunma, Japan
| | - Katsuya Osone
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
| | - Erkhem-Ochir Bilguun
- Division of Integrated Oncology Research, Gunma University, Initiative for Advanced Research (GIAR), Maebashi, Gunma, Japan
| | - Haruka Okami
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
| | - Yuki Shimoda
- Department of Diagnostic Pathology, Gunma University Graduate School of Medicine
| | - Takuya Shiraishi
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
| | - Takuhisa Okada
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
| | - Akihiko Sano
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
| | - Makoto Sakai
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
| | - Makoto Sohda
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
| | - Tatsuya Miyazaki
- Department of Gastroenterological Surgery, Maebashi Red Cross Hospital, Maebashi, Gunma, Japan
| | - Munenori Ide
- Department of Pathology Diagnosis, Maebashi Red Cross Hospital, Maebashi, Gunma, Japan
| | - Hiroomi Ogawa
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
| | - Takashi Yao
- Department of Human Pathology, Juntendo University Graduate School of Medicine, Bunkyouku, Tokyo, Japan
| | - Tetsunari Oyama
- Department of Diagnostic Pathology, Gunma University Graduate School of Medicine
| | - Ken Shirabe
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
| | - Hiroshi Saeki
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Gunma, Japan
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18
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Gravina AG, Pellegrino R, Cipullo M, Palladino G, Imperio G, Ventura A, Auletta S, Ciamarra P, Federico A. May ChatGPT be a tool producing medical information for common inflammatory bowel disease patients' questions? An evidence-controlled analysis. World J Gastroenterol 2024; 30:17-33. [PMID: 38293321 PMCID: PMC10823903 DOI: 10.3748/wjg.v30.i1.17] [Citation(s) in RCA: 16] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/04/2023] [Revised: 12/07/2023] [Accepted: 12/28/2023] [Indexed: 01/06/2024] Open
Abstract
Artificial intelligence is increasingly entering everyday healthcare. Large language model (LLM) systems such as Chat Generative Pre-trained Transformer (ChatGPT) have become potentially accessible to everyone, including patients with inflammatory bowel diseases (IBD). However, significant ethical issues and pitfalls exist in innovative LLM tools. The hype generated by such systems may lead to unweighted patient trust in these systems. Therefore, it is necessary to understand whether LLMs (trendy ones, such as ChatGPT) can produce plausible medical information (MI) for patients. This review examined ChatGPT's potential to provide MI regarding questions commonly addressed by patients with IBD to their gastroenterologists. From the review of the outputs provided by ChatGPT, this tool showed some attractive potential while having significant limitations in updating and detailing information and providing inaccurate information in some cases. Further studies and refinement of the ChatGPT, possibly aligning the outputs with the leading medical evidence provided by reliable databases, are needed.
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Affiliation(s)
- Antonietta Gerarda Gravina
- Division of Hepatogastroenterology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Raffaele Pellegrino
- Division of Hepatogastroenterology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Marina Cipullo
- Division of Hepatogastroenterology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Giovanna Palladino
- Division of Hepatogastroenterology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Giuseppe Imperio
- Division of Hepatogastroenterology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Andrea Ventura
- Division of Hepatogastroenterology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Salvatore Auletta
- Division of Hepatogastroenterology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Paola Ciamarra
- Division of Hepatogastroenterology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples 80138, Italy
| | - Alessandro Federico
- Division of Hepatogastroenterology, Department of Precision Medicine, University of Campania Luigi Vanvitelli, Naples 80138, Italy
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19
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Jayasooriya N, Pollok RC, Blackwell J, Bottle A, Petersen I, Creese H, Saxena S. Adherence to 5-aminosalicylic acid maintenance treatment in young people with ulcerative colitis: a retrospective cohort study in primary care. Br J Gen Pract 2023; 73:e850-e857. [PMID: 37666511 PMCID: PMC10498382 DOI: 10.3399/bjgp.2023.0006] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/03/2023] [Accepted: 05/16/2023] [Indexed: 09/06/2023] Open
Abstract
BACKGROUND Maintenance treatment with 5-aminosalicylic acid (5-ASA) is recommended in ulcerative colitis (UC), but accurate estimates of discontinuation and adherence in adolescents transitioning to young adulthood are lacking. AIM To determine rates and risk factors for discontinuation and adherence to oral 5-ASA in adolescents and young adults 1 year following diagnosis of UC. DESIGN AND SETTING Observational cohort study using the UK Clinical Practice Research Datalink among adolescents and young adults (aged 10-24 years) diagnosed with UC between 1 January 1998 and 1 May 2016. METHOD Time to oral 5-ASA discontinuation (days) and adherence rates (proportion of days covered) were calculated during the first year of treatment using Kaplan-Meier survival analysis. Cox regression models were built to estimate the impact of sociodemographic and health-related risk factors. RESULTS Among 607 adolescents and young adults starting oral 5-ASA maintenance treatment, one-quarter (n = 152) discontinued within 1 month and two- thirds (n = 419) within 1 year. Discontinuation was higher among those aged 18-24 years (74%) than younger age groups (61% and 56% in those aged 10-14 and 15-17 years, respectively). Adherence was lower among young adults than adolescents (69% in those aged 18-24 years versus 80% in those aged 10-14 years). Residents in deprived versus affluent postcodes were more likely to discontinue treatment (adjusted hazard ratio [aHR] 1.46, 95% confidence interval [CI] = 1.10 to 1.92). Early corticosteroid use for an acute flare lowered the likelihood of oral 5-ASA discontinuation (aHR 0.68, 95% CI = 0.51 to 0.90). CONCLUSION The first year of starting long-term therapies in adolescents and young adults diagnosed with UC is a critical window for active follow-up of maintenance treatment, particularly in those aged 18-24 years and those living in deprived postcodes.
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Affiliation(s)
- Nishani Jayasooriya
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
| | - Richard C Pollok
- Department of Gastroenterology, St George's University Hospitals NHS Foundation Trust, London, UK
| | | | - Alex Bottle
- School of Public Health, Imperial College London, London, UK
| | - Irene Petersen
- Department of Primary Care and Population Health, University College London, London, UK; Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark
| | - Hanna Creese
- School of Public Health, Imperial College London, London, UK
| | - Sonia Saxena
- School of Public Health, Imperial College London, London, UK
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20
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Schardey J, Lu C, Neumann J, Wirth U, Li Q, Jiang T, Zimmermann P, Andrassy J, Bazhin AV, Werner J, Kühn F. Differential Immune Infiltration Profiles in Colitis-Associated Colorectal Cancer versus Sporadic Colorectal Cancer. Cancers (Basel) 2023; 15:4743. [PMID: 37835436 PMCID: PMC10571767 DOI: 10.3390/cancers15194743] [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: 08/13/2023] [Revised: 09/21/2023] [Accepted: 09/24/2023] [Indexed: 10/15/2023] Open
Abstract
BACKGROUND Chronic inflammation is a significant factor in colorectal cancer (CRC) development, especially in colitis-associated CRC (CAC). T-cell exhaustion is known to influence inflammatory bowel disease (IBD) progression and antitumor immunity in IBD patients. This study aimed to identify unique immune infiltration characteristics in CAC patients. METHODS We studied 20 CAC and 20 sporadic CRC (sCRC) patients, who were matched by tumor stage, grade, and location. Immunohistochemical staining targeted various T-cell markers (CD3, CD4, CD8, and FOXP3), T-cell exhaustion markers (TOX and TIGIT), a B-cell marker (CD20), and a neutrophil marker (CD66b) in tumor and tumor-free mucosa from both groups. The quantification of the tumor immune stroma algorithm assessed immune-infiltrating cells. RESULTS CAC patients had significantly lower TOX+ cell infiltration than sCRC in tumors (p = 0.02) and paracancerous tissues (p < 0.01). Right-sided CAC showed increased infiltration of TOX+ cells (p = 0.01), FOXP3+ regulatory T-cells (p < 0.01), and CD20+ B-cells (p < 0.01) compared to left-sided CAC. In sCRC, higher tumor stages (III and IV) had significantly lower TIGIT+ infiltrate than stages I and II. In CAC, high CD3+ (p < 0.01) and CD20+ (p < 0.01) infiltrates correlated with improved overall survival. In sCRC, better survival was associated with decreased TIGIT+ cells (p < 0.038) and reduced CD8+ infiltrates (p = 0.02). CONCLUSION In CAC, high CD3+ and CD20+ infiltrates relate to improved survival, while this association is absent in sCRC. The study revealed marked differences in TIGIT and TOX expression, emphasizing distinctions between CAC and sCRC. T-cell exhaustion appears to have a different role in CAC development.
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Affiliation(s)
- Josefine Schardey
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Hospital Munich, 81377 Munich, Germany
| | - Can Lu
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Hospital Munich, 81377 Munich, Germany
- Department of Colorectal Surgery and Oncology (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education & Key Laboratory of Molecular Biology in Medical Sciences), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China
- Zhejiang Provincial Clinical Research Center for CANCER & Cancer Center of Zhejiang University, Zhejiang University School of Medicine, Hangzhou 310058, China
| | - Jens Neumann
- Department of Pathology, Ludwig-Maximilians University, 81377 Munich, Germany
| | - Ulrich Wirth
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Hospital Munich, 81377 Munich, Germany
| | - Qiang Li
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Hospital Munich, 81377 Munich, Germany
| | - Tianxiao Jiang
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Hospital Munich, 81377 Munich, Germany
| | - Petra Zimmermann
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Hospital Munich, 81377 Munich, Germany
| | - Joachim Andrassy
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Hospital Munich, 81377 Munich, Germany
| | - Alexandr V. Bazhin
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Hospital Munich, 81377 Munich, Germany
- German Cancer Consortium (DKTK), Partner Site Munich, 80336 Munich, Germany
| | - Jens Werner
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Hospital Munich, 81377 Munich, Germany
| | - Florian Kühn
- Department of General, Visceral and Transplant Surgery, Ludwig-Maximilians-University Hospital Munich, 81377 Munich, Germany
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21
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Okami H, Ozawa N, Sohda M, Yokobori T, Osone K, Erkhem-Ochir B, Dorjkhorloo G, Shiraishi T, Okada T, Sano A, Sakai M, Miyazaki T, Ogawa H, Yao T, Oike T, Sato H, Shirabe K, Shibata A, Saeki H. HLA Class I Expression Is Associated with DNA Damage and Immune Cell Infiltration into Dysplastic and Neoplastic Lesions in Ulcerative Colitis. Int J Mol Sci 2023; 24:13648. [PMID: 37686454 PMCID: PMC10487850 DOI: 10.3390/ijms241713648] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/26/2023] [Revised: 08/24/2023] [Accepted: 09/02/2023] [Indexed: 09/10/2023] Open
Abstract
Human leukocyte antigen class I (HLA-I) is considered a genetic pathogen for ulcerative colitis (UC). This study aimed to investigate the significance of DNA damage and HLA-I expression in infiltrating immune cells and immune checkpoint protein PD-L1 expression in dysplasia/colitic cancer (CC) and sporadic colorectal cancer (SCRC). We performed immunohistochemical staining for HLA-I, PD-L1, γH2AX (DNA damage marker), and immune cell markers such as CD8, FOXP3, CD68, and CD163 (in surgically resected specimens from 17 SCRC patients with 12 adjacent normal mucosa (NM) and 9 UC patients with 18 dysplasia/CC tumors. The ratio of membrane HLA-I-positive epithelial cells in UC and dysplasia/CC tissues was significantly higher than that in NM and SCRC. High HLA-I expression in dysplasia/CC was associated with high positivity of γH2AX and PD-L1 expression compared to SCRC. The infiltration of CD8-positive T cells and CD68-positive macrophages in HLA-I-high dysplasia/CC was significantly higher than in UC and SCRC. Dysplasia/CC specimens with DNA damage exhibited high levels of HLA-I-positive epithelial cells with high CD8- and CD68-positive immune cell infiltration compared to UC and SCRC specimens. Targeting DNA damage in UC may regulate immune cell infiltration, immune checkpoint proteins, and carcinogenesis by modulating DNA damage-induced HLA-I antigen presentation.
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Affiliation(s)
- Haruka Okami
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan; (H.O.); (N.O.); (K.O.); (G.D.); (T.S.); (T.O.); (A.S.); (M.S.); (H.O.); (K.S.); (H.S.)
| | - Naoya Ozawa
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan; (H.O.); (N.O.); (K.O.); (G.D.); (T.S.); (T.O.); (A.S.); (M.S.); (H.O.); (K.S.); (H.S.)
| | - Makoto Sohda
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan; (H.O.); (N.O.); (K.O.); (G.D.); (T.S.); (T.O.); (A.S.); (M.S.); (H.O.); (K.S.); (H.S.)
| | - Takehiko Yokobori
- Division of Integrated Oncology Research, Gunma University, Initiative for Advanced Research (GIAR), Maebashi 371-8511, Japan;
| | - Katsuya Osone
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan; (H.O.); (N.O.); (K.O.); (G.D.); (T.S.); (T.O.); (A.S.); (M.S.); (H.O.); (K.S.); (H.S.)
| | - Bilguun Erkhem-Ochir
- Division of Integrated Oncology Research, Gunma University, Initiative for Advanced Research (GIAR), Maebashi 371-8511, Japan;
| | - Gendensuren Dorjkhorloo
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan; (H.O.); (N.O.); (K.O.); (G.D.); (T.S.); (T.O.); (A.S.); (M.S.); (H.O.); (K.S.); (H.S.)
| | - Takuya Shiraishi
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan; (H.O.); (N.O.); (K.O.); (G.D.); (T.S.); (T.O.); (A.S.); (M.S.); (H.O.); (K.S.); (H.S.)
| | - Takuhisa Okada
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan; (H.O.); (N.O.); (K.O.); (G.D.); (T.S.); (T.O.); (A.S.); (M.S.); (H.O.); (K.S.); (H.S.)
| | - Akihiko Sano
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan; (H.O.); (N.O.); (K.O.); (G.D.); (T.S.); (T.O.); (A.S.); (M.S.); (H.O.); (K.S.); (H.S.)
| | - Makoto Sakai
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan; (H.O.); (N.O.); (K.O.); (G.D.); (T.S.); (T.O.); (A.S.); (M.S.); (H.O.); (K.S.); (H.S.)
| | - Tatsuya Miyazaki
- Department of Surgery Japanese Red Cross Maebashi Hospital, Maebashi 371-0811, Japan;
| | - Hiroomi Ogawa
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan; (H.O.); (N.O.); (K.O.); (G.D.); (T.S.); (T.O.); (A.S.); (M.S.); (H.O.); (K.S.); (H.S.)
| | - Takashi Yao
- Department of Human Pathology, Graduate School of Medicine, Juntendo University, Bunkyo-ku 113-8431, Japan;
| | - Takahiro Oike
- Department of Radiation Oncology, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan; (T.O.); (H.S.)
| | - Hiro Sato
- Department of Radiation Oncology, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan; (T.O.); (H.S.)
| | - Ken Shirabe
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan; (H.O.); (N.O.); (K.O.); (G.D.); (T.S.); (T.O.); (A.S.); (M.S.); (H.O.); (K.S.); (H.S.)
| | - Atsushi Shibata
- Division of Molecular Oncological Pharmacy, Faculty of Pharmacy, Keio University, Minato-ku 108-8345, Japan;
| | - Hiroshi Saeki
- Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi 371-8510, Japan; (H.O.); (N.O.); (K.O.); (G.D.); (T.S.); (T.O.); (A.S.); (M.S.); (H.O.); (K.S.); (H.S.)
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22
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Aust DE, Baretton GB, Sommer U. [Ulcerative colitis-associated carcinogenesis : An update]. PATHOLOGIE (HEIDELBERG, GERMANY) 2023; 44:294-300. [PMID: 37311872 DOI: 10.1007/s00292-023-01207-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Accepted: 05/16/2023] [Indexed: 06/15/2023]
Abstract
Ulcerative colitis (UC) is a chronic inflammatory bowel disease beginning in the rectum and gradually extending to the right-sided colon and the terminal ileum (backwash-ileitis). Its causes are still not completely understood. Genetic susceptibility, changes in the microbiota and immune response, as well as environmental factors are thought to influence the disease course.Patients with UC are at increased risk of developing colorectal cancer (CRC) when compared to an age-matched normal population. Cancer risk increases with early onset, duration, and extent of the disease, with development of strictures, intraepithelial neoplasia, and concomitant primary sclerosing cholangitis.In contrast to the sporadic adenoma-carcinoma-sequence, UC-related CRC develops through an inflammation-intraepithelial neoplasia-carcinoma-sequence, in which genetic alterations already occur in the inflamed epithelium before the development of intraepithelial neoplasia.This article summarizes the current state of knowledge regarding UC-related carcinogenesis and its possible impact on prevention and therapy.
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Affiliation(s)
- Daniela E Aust
- Institut für Pathologie, Universitätsklinikum Carl Gustav Carus Dresden an der TU Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland.
| | - Gustavo B Baretton
- Institut für Pathologie, Universitätsklinikum Carl Gustav Carus Dresden an der TU Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland
| | - Ulrich Sommer
- Institut für Pathologie, Universitätsklinikum Carl Gustav Carus Dresden an der TU Dresden, Fetscherstr. 74, 01307, Dresden, Deutschland
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23
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Sato Y, Tsujinaka S, Miura T, Kitamura Y, Suzuki H, Shibata C. Inflammatory Bowel Disease and Colorectal Cancer: Epidemiology, Etiology, Surveillance, and Management. Cancers (Basel) 2023; 15:4154. [PMID: 37627182 PMCID: PMC10452690 DOI: 10.3390/cancers15164154] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2023] [Revised: 07/13/2023] [Accepted: 08/16/2023] [Indexed: 08/27/2023] Open
Abstract
Patients with inflammatory bowel diseases (IBDs), such as ulcerative colitis and Crohn's disease, have an increased risk of developing colorectal cancer (CRC). Although advancements in endoscopic imaging techniques, integrated surveillance programs, and improved medical therapies have contributed to a decreased incidence of CRC in patients with IBD, the rate of CRC remains higher in patients with IBD than in individuals without chronic colitis. Patients with IBD-related CRCs exhibit a poorer prognosis than those with sporadic CRCs, owing to their aggressive histological characteristics and lower curative resection rate. In this review, we present an updated overview of the epidemiology, etiology, risk factors, surveillance strategies, treatment recommendations, and prognosis of IBD-related CRCs.
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Affiliation(s)
| | - Shingo Tsujinaka
- Division of Gastroenterological Surgery, Department of Surgery, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, Japan
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24
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Dan WY, Zhou GZ, Peng LH, Pan F. Update and latest advances in mechanisms and management of colitis-associated colorectal cancer. World J Gastrointest Oncol 2023; 15:1317-1331. [PMID: 37663937 PMCID: PMC10473934 DOI: 10.4251/wjgo.v15.i8.1317] [Citation(s) in RCA: 1] [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: 03/30/2023] [Revised: 07/03/2023] [Accepted: 07/25/2023] [Indexed: 08/10/2023] Open
Abstract
Colitis-associated colorectal cancer (CAC) is defined as a specific cluster of colorectal cancers that develop as a result of prolonged colitis in patients with inflammatory bowel disease (IBD). Patients with IBD, including ulcerative colitis and Crohn's disease, are known to have an increased risk of developing CAC. Although the incidence of CAC has significantly decreased over the past few decades, individuals with CAC have increased mortality compared to individuals with sporadic colorectal cancer, and the incidence of CAC increases with duration. Chronic inflammation is generally recognized as a major contributor to the pathogenesis of CAC. CAC has been shown to progress from colitis to dysplasia and finally to carcinoma. Accumulating evidence suggests that multiple immune-mediated pathways, DNA damage pathways, and pathogens are involved in the pathogenesis of CAC. Over the past decade, there has been an increasing effort to develop clinical approaches that could help improve outcomes for CAC patients. Colonoscopic surveillance plays an important role in reducing the risk of advanced and interval cancers. It is generally recommended that CAC patients undergo endoscopic removal or colectomy. This review summarizes the current understanding of CAC, particularly its epidemiology, mechanisms, and management. It focuses on the mechanisms that contribute to the development of CAC, covering advances in genomics, immunology, and the microbiome; presents evidence for management strategies, including endoscopy and colectomy; and discusses new strategies to interfere with the process and development of CAC. These scientific findings will pave the way for the management of CAC in the near future.
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Affiliation(s)
- Wan-Yue Dan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- Medical School, Nankai University, Tianjin 300071, China
| | - Guan-Zhou Zhou
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- Medical School, Nankai University, Tianjin 300071, China
| | - Li-Hua Peng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Fei Pan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
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25
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Seishima R, Okabayashi K, Ikeuchi H, Uchino M, Futami K, Noguchi T, Ohge H, Iseki Y, Watanabe K, Itabashi M, Okamoto K, Toiyama Y, Ogino T, Nakamura M, Yamada K, Wakai T, Sato Y, Kimura H, Takahashi K, Hida K, Kinugasa Y, Ishida F, Okuda J, Daito K, Koyama F, Ueno H, Yamamoto T, Yamamoto S, Hanai T, Maemoto A, Arakaki J, Komori K, Akagi Y, Shida D, Yamaguchi S, Matsuda K, Maeda K, Noake T, Nezu R, Sasaki S, Hasegawa J, Sunami E, Kanemitsu Y, Katsumata K, Uehara K, Kiyomatsu T, Suto T, Kazama S, Yamada T, Goi T, Ishihara S, Ajioka Y, Sugihara K. Effect of Biologics on the Risk of Advanced-Stage Inflammatory Bowel Disease-Associated Intestinal Cancer: A Nationwide Study. Am J Gastroenterol 2023; 118:1248-1255. [PMID: 36622356 DOI: 10.14309/ajg.0000000000002149] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/08/2022] [Accepted: 11/21/2022] [Indexed: 01/10/2023]
Abstract
INTRODUCTION The aim of this study was to evaluate the effect of biologics on the risk of advanced-stage inflammatory bowel disease (IBD)-associated intestinal cancer from a nationwide multicenter data set. METHODS The medical records of patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed with IBD-associated intestinal neoplasia (dysplasia or cancer) from 1983 to 2020 were included in this study. Therapeutic agents were classified into 3 types: biologics, 5-aminosalicylic acid, and immunomodulators. The pathological cancer stage was compared based on the drug used in both patients with CD and UC. RESULTS In total, 1,042 patients (214 CD and 828 UC patients) were included. None of the drugs were significantly associated with cancer stage in the patients with CD. In the patients with UC, an advanced cancer stage was significantly associated with less use of biologics (early stage: 7.7% vs advanced stage: 2.0%, P < 0.001), 5-aminosalicylic acid, and immunomodulators. Biologic use was associated with a lower incidence of advanced-stage cancer in patients diagnosed by regular surveillance (biologics [-] 24.5% vs [+] 9.1%, P = 0.043), but this was not the case for the other drugs. Multivariate analysis showed that biologic use was significantly associated with a lower risk of advanced-stage disease (odds ratio = 0.111 [95% confidence interval, 0.034-0.356], P < 0.001). DISCUSSION Biologic use was associated with a lower risk of advanced IBD-associated cancer in patients with UC but not with CD. The mechanism of cancer progression between UC and CD may be different and needs to be further investigated.
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Affiliation(s)
- Ryo Seishima
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Koji Okabayashi
- Department of Surgery, Keio University School of Medicine, Tokyo, Japan
| | - Hiroki Ikeuchi
- Department of Gastroenterological Surgery, Division of Inflammatory Bowel Disease, Hyogo Medical University, Hyogo, Japan
| | - Motoi Uchino
- Department of Gastroenterological Surgery, Division of Inflammatory Bowel Disease, Hyogo Medical University, Hyogo, Japan
| | - Kitaro Futami
- Department of Surgery, Fukuoka University Chikushi Hospital, Fukuoka, Japan
| | - Tatsuki Noguchi
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Hiroki Ohge
- Department of Infectious Diseases, Hiroshima University Hospital, Hiroshima, Japan
| | - Yasuhito Iseki
- Surgical Medicine, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Kazuhiro Watanabe
- Department of Surgery, Tohoku University School of Medicine, Miyagi, Japan
| | - Michio Itabashi
- Department of Surgery, Division of Inflammatory Bowel Disease Surgery, Tokyo Women's Medical University, Tokyo, Japan
| | - Kinya Okamoto
- Japan Community Health Care Organization, Tokyo Yamate Medical Center, Tokyo, Japan
| | - Yuji Toiyama
- Department of Gastrointestinal and Paediatric Surgery, Mie University Graduate School of Medicine, Mie, Tokyo
| | - Takayuki Ogino
- Department of Gastrointestinal Surgery, Osaka University Graduate School of Medicine, Osaka, Japan
| | - Masafumi Nakamura
- Kyushu University Department of Surgery and Oncology, Graduate School of Medical Sciences, Fukuoka, Japan
| | | | - Toshifumi Wakai
- Division of Digestive and General Surgery, Niigata University, Niigata, Japan
| | - Yu Sato
- Department of Surgery, Toho University Sakura Medical Center, Chiba, Japan
| | - Hideaki Kimura
- Inflammatory Bowel Disease Center, Yokohama City University Medical Center, Kanagawa, Japan
| | - Kenichi Takahashi
- Inflammatory Bowel Disease Center, Tohoku Rosai Hospital, Miyagi, Japan
| | - Koya Hida
- Department of Gastrointestinal Surgery, Kyoto University Graduate School of Medicine, Kyoto, Japan
| | - Yusuke Kinugasa
- Department of Gastrointestinal Surgery, Tokyo Medical and Dental University, Tokyo, Japan
| | - Fumio Ishida
- Digestive Disease Center, Showa University Northern Yokohama Hospital, Kanagawa, Japan
| | - Junji Okuda
- Cancer Center, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Koji Daito
- Department of Surgery, Faculty of Medicine, Kindai University, Osaka, Japan
| | | | - Hideki Ueno
- Department of Surgery, National Defense Medical College, Saitama, Japan
| | - Takayuki Yamamoto
- Japan Community Health Care Organization, Yokkaichi Hazu Medical Center, Mie, Japan
| | - Seiichiro Yamamoto
- Department of Digestive System Surgery, Tokai University School of Medicine, Kanagawa, Japan
| | - Tsunekazu Hanai
- Department of Surgery, School of Medicine, Fujita Health University, Aichi, Japan
| | - Atsuo Maemoto
- Institute of Biomedical Research, Sapporo-Higashi Tokushukai Hospital, Hokkaido, Japan
| | - Junya Arakaki
- Department of Surgery, Center for Gastroenterology, Urasoe General Hospital Okinawa, Japan
| | - Koji Komori
- Department of Gastroenterological Surgery, Aichi Cancer Center Hospital, Aichi, Japan
| | - Yoshito Akagi
- Department of Surgery, Kurume University School of Medicine, Fukuoka, Japan
| | - Dai Shida
- Department of Surgery, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan
| | - Shigeki Yamaguchi
- Department of Gastrointestinal Surgery, Saitama Medical University International Medical Center, Saitama, Japan
| | - Keiji Matsuda
- Department of Surgery, Teikyo University School of Medicine, Tokyo, Japan
| | - Kiyoshi Maeda
- Department of Gastroenterological Surgery, Osaka City General Hospital, Osaka, Japan
| | | | - Riichiro Nezu
- Department of Surgery, Nishinomiya Municipal Central Hospital, Hyogo, Japan
| | - Shin Sasaki
- Department of Coloproctological Surgery, Japanese Red Cross Medical Center, Tokyo, Japan
| | | | - Eiji Sunami
- Department of Surgery, Kyorin University, Tokyo, Japan
| | - Yukihide Kanemitsu
- Department of Colorectal Surgery, National Cancer Center Hospital, Tokyo, Japan
| | - Kenji Katsumata
- Department of Gastrointestinal and Paediatric Surgery, Tokyo Medical University, Tokyo, Japan
| | - Kei Uehara
- Division of Surgical Oncology, Department of Surgery, Nagoya University Graduate School of Medicine, Aichi, Japan
| | - Tomomichi Kiyomatsu
- Department of Surgery, National Center for Global Health and Medicine, Tokyo, Japan
| | - Takeshi Suto
- Department of Gastroenterological Surgery, Yamagata Prefectural Central Hospital, Yamagata, Japan
| | - Shinsuke Kazama
- Division of Gastroenterological Surgery, Saitama Cancer Center, Saitama, Japan
| | - Takeshi Yamada
- Department of Gastrointestinal and Hepato-Biliary-Pancreatic Surgery, Nippon Medical School, Tokyo, Japan
| | - Takenori Goi
- First Department of Surgery, Faculty of Medical Sciences, University of Fukui, Fukui, Japan
| | - Soichiro Ishihara
- Department of Surgical Oncology, The University of Tokyo, Tokyo, Japan
| | - Yoichi Ajioka
- Division of Molecular and Diagnostic Pathology, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan; and
| | - Kenichi Sugihara
- Department of Surgery, Tokyo Medical and Dental University, Tokyo, Japan
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Słoka J, Madej M, Strzalka-Mrozik B. Molecular Mechanisms of the Antitumor Effects of Mesalazine and Its Preventive Potential in Colorectal Cancer. Molecules 2023; 28:5081. [PMID: 37446747 DOI: 10.3390/molecules28135081] [Citation(s) in RCA: 10] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2023] [Revised: 06/18/2023] [Accepted: 06/27/2023] [Indexed: 07/15/2023] Open
Abstract
Chemoprevention is one of the ways to fight colorectal cancer, which is a huge challenge in oncology. Numerous pieces of evidence indicate that chronic inflammation in the course of Crohn's disease or ulcerative colitis (UC) is a significant cancer risk factor. Epidemiologic studies suggest that long-term use of non-steroidal anti-inflammatory drugs (NSAIDs), including mesalazine, has beneficial effects on colitis-associated colorectal cancer. Mesalazine is a first-line therapy for UC and is also widely used for maintaining remission in UC. Data showed that mesalazine has antiproliferative properties associated with cyclooxygenase (COX) inhibition but can also act through COX-independent pathways. This review summarizes knowledge about mesalazine's molecular mechanisms of action and chemopreventive effect by which it could interfere with colorectal cancer cell proliferation and survival.
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Affiliation(s)
- Joanna Słoka
- Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland
| | - Marcel Madej
- Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland
| | - Barbara Strzalka-Mrozik
- Department of Molecular Biology, Faculty of Pharmaceutical Sciences in Sosnowiec, Medical University of Silesia, 40-055 Katowice, Poland
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Conceição D, Saraiva MR, Rosa I, Claro I. Inflammatory Bowel Disease Treatment in Cancer Patients-A Comprehensive Review. Cancers (Basel) 2023; 15:3130. [PMID: 37370740 DOI: 10.3390/cancers15123130] [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: 04/30/2023] [Revised: 05/30/2023] [Accepted: 06/07/2023] [Indexed: 06/29/2023] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic disease for which medical treatment with immunomodulating drugs is increasingly used earlier to prevent disability. Additionally, cancer occurrence in IBD patients is increased for several reasons, either IBD-related or therapy-associated. Doctors are therefore facing the challenge of managing patients with IBD and a past or current malignancy and the need to balance the risk of cancer recurrence associated with immunosuppressive drugs with the potential worsening of IBD activity if they are withdrawn. This review aims to explore the features of different subtypes of cancer occurring in IBD patients to present current evidence on malignancy recurrence risk associated with IBD medical therapy along with the effects of cancer treatment in IBD and finally to discuss current recommendations on the management of these patients. Due to sparse data, a case-by-case multidisciplinary discussion is advised, including inputs from the gastroenterologist, oncologist, and patient.
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Affiliation(s)
- Daniel Conceição
- Department of Gastroenterology, Instituto Português de Oncologia de Lisboa Francisco Gentil, 1099-023 Lisboa, Portugal
| | - Margarida R Saraiva
- Department of Gastroenterology, Instituto Português de Oncologia de Lisboa Francisco Gentil, 1099-023 Lisboa, Portugal
| | - Isadora Rosa
- Department of Gastroenterology, Instituto Português de Oncologia de Lisboa Francisco Gentil, 1099-023 Lisboa, Portugal
| | - Isabel Claro
- Department of Gastroenterology, Instituto Português de Oncologia de Lisboa Francisco Gentil, 1099-023 Lisboa, Portugal
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Nardone OM, Zammarchi I, Santacroce G, Ghosh S, Iacucci M. Inflammation-Driven Colorectal Cancer Associated with Colitis: From Pathogenesis to Changing Therapy. Cancers (Basel) 2023; 15:cancers15082389. [PMID: 37190315 DOI: 10.3390/cancers15082389] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/20/2023] [Revised: 04/15/2023] [Accepted: 04/18/2023] [Indexed: 05/17/2023] Open
Abstract
Patients affected by inflammatory bowel disease (IBD) have a two-fold higher risk of developing colorectal cancer (CRC) than the general population. IBD-related CRC follows a different genetic and molecular pathogenic pathway than sporadic CRC and can be considered a complication of chronic intestinal inflammation. Since inflammation is recognised as an independent risk factor for neoplastic progression, clinicians strive to modulate and control disease, often using potent therapy agents to achieve mucosal healing and decrease the risk of colorectal cancer in IBD patients. Improved therapeutic control of inflammation, combined with endoscopic advances and early detection of pre-cancerous lesions through surveillance programs, explains the lower incidence rate of IBD-related CRC. In addition, current research is increasingly focused on translating emerging and advanced knowledge in microbiome and metagenomics into personalised, early, and non-invasive CRC screening tools that guide organ-sparing therapy in IBD patients. This review aims to summarise the existing literature on IBD-associated CRC, focusing on new insights into the alteration of the intestinal barrier and the interactions with the gut microbiome as the initial promoter. In addition, the role of OMIC techniques for precision medicine and the impact of the available IBD therapeutic armamentarium on the evolution to CRC will be discussed.
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Affiliation(s)
- Olga Maria Nardone
- Department of Public Health, University Federico II of Naples, 80131 Naples, Italy
| | - Irene Zammarchi
- Department of Medicine, University College of Cork, T12 R229 Cork, Ireland
| | | | - Subrata Ghosh
- Department of Medicine, University College of Cork, T12 R229 Cork, Ireland
| | - Marietta Iacucci
- Department of Medicine, University College of Cork, T12 R229 Cork, Ireland
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Eder P, Łodyga M, Gawron-Kiszka M, Dobrowolska A, Gonciarz M, Hartleb M, Kłopocka M, Małecka-Wojciesko E, Radwan P, Reguła J, Zagórowicz E, Banasiewicz T, Durlik M, Rydzewska G. Guidelines for the management of ulcerative colitis. Recommendations of the Polish Society of Gastroenterology and the Polish National Consultant in Gastroenterology. PRZEGLAD GASTROENTEROLOGICZNY 2023; 18:1-42. [PMID: 37007752 PMCID: PMC10050986 DOI: 10.5114/pg.2023.125882] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 02/24/2023] [Indexed: 03/17/2023]
Abstract
This paper is an update of the diagnostic and therapeutic recommendations of the National Consultant for Gastroenterology and the Polish Society of Gastroenterology from 2013. It contains 49 recommendations for the diagnosis and treatment, both pharmacological and surgical, of ulcerative colitis in adults. The guidelines were developed by a group of experts appointed by the Polish Society of Gastroenterology and the National Consultant in the field of Gastroenterology. The methodology related to the GRADE methodology was used to assess the quality of available evidence and the strength of therapeutic recommendations. The degree of expert support for the proposed statements was assessed on a 6-point Likert scale. Voting results, together with comments, are included with each statement.
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Affiliation(s)
- Piotr Eder
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, Poznan University Clinical Hospital, Poznan, Poland
| | - Michał Łodyga
- Department of Internal Medicine, Faculty of Health Science, Medical University of Warsaw, Warsaw, Poland
| | - Magdalena Gawron-Kiszka
- Department of Gastroenterology and Hepatology, Medical University of Silesia, Katowice, Poland
| | - Agnieszka Dobrowolska
- Department of Gastroenterology, Dietetics and Internal Medicine, Poznan University of Medical Sciences, Poznan University Clinical Hospital, Poznan, Poland
| | - Maciej Gonciarz
- Department of Gastroenterology and Internal Medicine, Military Institute of Medicine, Warsaw, Poland
| | - Marek Hartleb
- Department of Gastroenterology and Hepatology, Medical University of Silesia, Katowice, Poland
| | - Maria Kłopocka
- Department of Gastroenterology and Nutrition Disorders, Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University in Torun, Poland
| | | | - Piotr Radwan
- Chair and Department of Gastroenterology with Endoscopy Unit, Medical University of Lublin, Lublin, Poland
| | - Jarosław Reguła
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Edyta Zagórowicz
- Department of Oncological Gastroenterology, Maria Sklodowska-Curie National Research Institute of Oncology, Warsaw, Poland
- Department of Gastroenterology, Hepatology and Clinical Oncology, Centre of Postgraduate Medical Education, Warsaw, Poland
| | - Tomasz Banasiewicz
- Department of General, Endocrinological and Gastroenterological Oncology Surgery, Poznan University of Medical Sciences, Poznan University Clinical Hospital, Poznan, Poland
| | - Marek Durlik
- Department of Gastroenterological Surgery and Transplantology, National Medical Institute of Ministry of Inferior and Administration, Warsaw, Poland
| | - Grażyna Rydzewska
- Department of Gastroenterology with the Inflammatory Bowel Disease Subdivision, National Medical Institute of Ministry of Inferior and Administration, Warsaw, Poland
- Collegium Medicum, Jan Kochanowski University, Kielce, Poland
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Newman P, Muscat J. Potential Role of Non-Steroidal Anti-Inflammatory Drugs in Colorectal Cancer Chemoprevention for Inflammatory Bowel Disease: An Umbrella Review. Cancers (Basel) 2023; 15:cancers15041102. [PMID: 36831446 PMCID: PMC9954537 DOI: 10.3390/cancers15041102] [Citation(s) in RCA: 5] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/12/2022] [Revised: 01/31/2023] [Accepted: 02/02/2023] [Indexed: 02/11/2023] Open
Abstract
Inflammatory Bowel Disease (IBD) is a category of autoimmune diseases that targets the destruction of the gastrointestinal system and includes both Crohn's Disease and Ulcerative Colitis (UC). Patients with IBD are at a higher risk of developing colorectal cancer (CRC) throughout their lives due to chronically increased inflammation. Nonsteroidal anti-inflammatory drugs (NSAIDs) are potential chemopreventative agents that can inhibit the development of CRC in persons without IBD. However, the use of NSAIDs for CRC chemoprevention in IBD patients is further complicated by NSAIDs' induction of damage to the bowel mucosal layer and ulcer formation. There has been a push in new research on chemopreventative properties of certain NSAIDs for IBD. The purpose of this umbrella review is to investigate the potential of low-dose NSAID compounds as chemopreventative agents for patients with IBD. This paper will also suggest future areas of research in the prevention of CRC for patients with IBD.
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Laredo V, García-Mateo S, Martínez-Domínguez SJ, López de la Cruz J, Gargallo-Puyuelo CJ, Gomollón F. Risk of Cancer in Patients with Inflammatory Bowel Diseases and Keys for Patient Management. Cancers (Basel) 2023; 15:871. [PMID: 36765829 PMCID: PMC9913122 DOI: 10.3390/cancers15030871] [Citation(s) in RCA: 33] [Impact Index Per Article: 16.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/12/2023] [Revised: 01/26/2023] [Accepted: 01/27/2023] [Indexed: 02/01/2023] Open
Abstract
Chronic inflammation in patients with Inflammatory Bowel Disease (IBD) leads to an increased risk of colorectal cancer, small bowel cancer, intestinal lymphoma and cholangiocarcinoma. However, treatments for IBD have also been associated with an increased risk of neoplasms. Patients receiving Thiopurines (TPs) have an increased risk of hematologic malignancies, non-melanoma skin cancer, urinary tract neoplasms and cervical cancer. Anti-TNFs have been associated with a higher risk of neoplasms, mainly lymphomas and melanomas; however, the data are controversial, and some recent studies do not confirm the association. Nevertheless, other biologic agents, such as ustekinumab and vedolizumab, have not shown an increased risk of any neoplasm to date. The risk of malignancies with tofacitinib exists, but its magnitude and relationship with previous treatment with TPs is not defined, so more studies from daily clinical practice are needed. Although biologic therapy seems to be safe for patients with current cancer or a prior history of cancer, as has been demonstrated in other chronic inflammatory conditions, prospective studies in this specific population are needed. Until that time, it is crucial to manage such conditions via the combined clinical expertise of the gastroenterologist and oncologist.
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Affiliation(s)
- Viviana Laredo
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
| | - Sandra García-Mateo
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
| | - Samuel J. Martínez-Domínguez
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
| | - Julia López de la Cruz
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
| | - Carla J. Gargallo-Puyuelo
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
| | - Fernando Gomollón
- Department of Gastroenterology, Lozano Blesa University Hospital, 50009 Zaragoza, Spain
- Aragón Health Research Institute (IIS Aragón), 50009 Zaragoza, Spain
- School of Medicine, University of Zaragoza, 50009 Zaragoza, Spain
- CIBER for Liver and Digestive Diseases (CIBERehd), 28029 Madrid, Spain
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Gonzalez M, Stephens M. 5-Aminosalicylate Therapy. PEDIATRIC INFLAMMATORY BOWEL DISEASE 2023:339-347. [DOI: 10.1007/978-3-031-14744-9_25] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/02/2025]
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Hsiao SW, Yen HH, Chen YY. Chemoprevention of Colitis-Associated Dysplasia or Cancer in Inflammatory Bowel Disease. Gut Liver 2022; 16:840-848. [PMID: 35670121 PMCID: PMC9668496 DOI: 10.5009/gnl210479] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/16/2021] [Revised: 11/20/2021] [Accepted: 12/07/2021] [Indexed: 08/27/2023] Open
Abstract
The association between inflammatory bowel disease and colorectal cancer is well known. Although the overall incidence of inflammatory bowel disease has declined recently, patients with this disease still have a 1.7-fold increased risk of colorectal cancer. The risk factors for developing colorectal cancer include extensive colitis, young age at diagnosis, disease duration, primary sclerosing cholangitis, chronic colonic mucosal inflammation, dysplasia lesion, and post-inflammatory polyps. In patients with inflammatory bowel disease, control of chronic inflammation and surveillance colonoscopies are important for the prevention of colorectal cancer. The 2017 guidelines from the European Crohn's and Colitis Organisation suggest that colonoscopies to screen for colorectal cancer should be performed when inflammatory bowel disease symptoms have lasted for 8 years. Current evidence supports the use of chemoprevention therapy with mesalamine to reduce the risk of colorectal cancer in patients with ulcerative colitis. Other compounds, including thiopurine, folic acid, statin, and tumor necrosis factor-α inhibitor, are controversial. Large surveillance cohort studies with longer follow-up duration are needed to evaluate the impact of drugs on colorectal cancer risks.
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Affiliation(s)
- Shun-Wen Hsiao
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
- Division of Gastroenterology, Yuanlin Christian Hospital, Changhua, Taiwan
| | - Hsu-Heng Yen
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
- General Education Center, Chienkuo Technology University, Changhua, Taiwan
- Department of Electrical Engineering, Chung Yuan Christian University, Taoyuan, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Yang-Yuan Chen
- Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan
- Division of Gastroenterology, Yuanlin Christian Hospital, Changhua, Taiwan
- Department of Hospitality Management, MingDao University, Changhua, Taiwan
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Marabotto E, Kayali S, Buccilli S, Levo F, Bodini G, Giannini EG, Savarino V, Savarino EV. Colorectal Cancer in Inflammatory Bowel Diseases: Epidemiology and Prevention: A Review. Cancers (Basel) 2022; 14:cancers14174254. [PMID: 36077786 PMCID: PMC9454776 DOI: 10.3390/cancers14174254] [Citation(s) in RCA: 26] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/02/2022] [Revised: 08/27/2022] [Accepted: 08/29/2022] [Indexed: 12/24/2022] Open
Abstract
Simple Summary Colorectal cancer (CRC) is one of the most serious potential complications of inflammatory bowel diseases (IBDs). The aging of patients affected by IBDs makes this issue a challenge that will increasingly be faced by clinicians in clinical practice, especially in light of the poorer prognosis for CRC in this group of people when compared with the general population. In this review, we summarize the current epidemiology, risk factors and various prevention strategies proposed for CRC in patients with IBDs. Abstract Colorectal cancer (CRC) is currently the third most frequent form of malignancy and the second in terms of mortality. Inflammatory bowel diseases (IBDs) are recognized risk factors for this type of cancer. Despite a worldwide increase in the incidence of CRC, the risk of CRC-related death in IBD patients has declined over time, probably because of successful surveillance strategies, the use of more effective drugs in the management of remission and improved indications to colectomy. This notwithstanding, CRC 5-year survival in patients with IBD is poorer than in the general population. This review provides a summary of the epidemiological features, risk factors and various prevention strategies proposed for CRC in IBD patients. Moreover, there is a special focus on reporting and highlighting the various prevention strategies proposed by the most important international scientific societies, both in terms of chemoprevention and endoscopic surveillance. Indeed, in conducting the analysis, we have given attention to the current primary, secondary and tertiary prevention guidelines, attempting to emphasize unresolved research and clinical problems related to this topic in order to improve diagnostic strategies and management.
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Affiliation(s)
- Elisa Marabotto
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, University of Genoa, 16132 Genoa, Italy
| | - Stefano Kayali
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, University of Genoa, 16132 Genoa, Italy
- Correspondence:
| | - Silvia Buccilli
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, University of Genoa, 16132 Genoa, Italy
| | - Francesca Levo
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, University of Genoa, 16132 Genoa, Italy
| | - Giorgia Bodini
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, University of Genoa, 16132 Genoa, Italy
| | - Edoardo G. Giannini
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, University of Genoa, 16132 Genoa, Italy
| | - Vincenzo Savarino
- Gastroenterology Unit, Department of Internal Medicine, IRCCS Ospedale Policlinico San Martino, University of Genoa, 16132 Genoa, Italy
| | - Edoardo Vincenzo Savarino
- Department of Surgery, Oncology and Gastroenterology, University of Padua, 35137 Padua, Italy
- Gastroenterology Unit, Azienda Ospedale Università di Padova, 35128 Padua, Italy
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Analysis of the Therapeutic Effect of Changyanning on Intestinal Flora in Inflammatory Bowel Disease. CONTRAST MEDIA & MOLECULAR IMAGING 2022; 2022:3757763. [PMID: 35845725 PMCID: PMC9242759 DOI: 10.1155/2022/3757763] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 05/11/2022] [Revised: 06/06/2022] [Accepted: 06/07/2022] [Indexed: 11/29/2022]
Abstract
Research Purposes. Inflammatory bowel disease (IBD) is an autoimmune disease coinduced by genes, environment, and immune response, mainly including ulcerative colitis (UC) and Crohn's disease (CD). There are a large number and variety of intestinal bacteria in the human intestinal tract. These bacteria maintain a balance with the human environment and participate in the normal physiological processes of the human body. They play a unique role in defending against pathogen invasion, maintaining the homeostasis of the human immune system and metabolizing substances. Intestinal flora imbalance may be one of the pathogenic factors of IBD, and restoring the disturbed intestinal flora has become a research hotspot in the prevention and treatment of IBD. Changyanning is mainly composed of Dijincao grass, yellow hairy ear grass, camphor tree roots, maple leaves, and so on. Clinical studies have shown that Changyanning alone or in combination has a significant effect on ulcerative colitis, but the treatment mechanism is not yet clear. In this study, we established an IBD animal model to explore the therapeutic mechanism of Changyanning on inflammatory bowel disease and its effect on intestinal flora. Research Methods. Male C57BL/6 SPF mice were given free access to 4% dextran sulfate sodium (DSS) solution for 7 days to establish an ulcerative colitis model. After the model was established, different doses of Changyanning tablets, Changyanning granules, and sulfasalazine were given by gavage for 7 days. The relieving effects of the above drugs on the symptoms of inflammatory bowel disease were evaluated by evaluating the mouse/rat body weight, survival rate, disease activity index, colon length, pathological tissue score, and other indicators. Results. The DSS-induced IBD mouse model showed significant increases in weight loss, DAI score, and pathological score. Both Changyanning tablets and granules can relieve the weight loss of mice, restore the colon length, and protect the colon tissue structure of mice. In reducing DAI and pathological scores in mice, Changyanning granules had a better effect. In conclusion, Changyanning can significantly improve the quality of life of IBD model animals, relieve intestinal inflammatory response, and relieve colonic edema, ulceration, and necrosis. The results show that Changyanning has a certain therapeutic effect on IBD. This study also provides experimental evidence for the application of Changyanning in the treatment of IBD, which is of great significance to its clinical application. The trail is registered in ChiCTR with number (TRN) ChiCTR2000028830.
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Cai C, Lu J, Lai L, Song D, Shen J, Tong J, Zheng Q, Wu K, Qian J, Ran Z. Drug therapy and monitoring for inflammatory bowel disease: a multinational questionnaire investigation in Asia. Intest Res 2022; 20:213-223. [PMID: 35508955 PMCID: PMC9081996 DOI: 10.5217/ir.2021.00031] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/19/2021] [Accepted: 02/07/2022] [Indexed: 11/17/2022] Open
Abstract
Background/Aims The incidence and prevalence of inflammatory bowel disease (IBD) is rising in Asia recently. The study aimed to obtain a comprehensive understanding of the current status of drug therapy and monitoring for IBD in Asia. Methods A questionnaire investigation on drug therapy and monitoring for IBD was conducted right before the 6th Annual Meeting of Asian Organization for Crohn’s & Colitis. Questionnaires were provided to Asian physicians to fill out via emails between March and May 2018. Results In total, responses of 166 physicians from 129 medical centers were included for analysis. Among the surveyed regions, the most average number of IBD specialist gastroenterologists and nurses was 4.8 per center in Taiwan and 2.5 per center in Mainland China, respectively. 5-Aminosalicylic acid/sulfasalazine (99.4%) was the most preferred first-line choice for mild-moderate ulcerative colitis (UC), meanwhile corticosteroid (83.7%) was widely applied for severe UC. The first-line medication for Crohn’s disease (CD) markedly varied as corticosteroid (68.1%) was the most favored in Mainland China, Japan, and South Korea, followed by infliximab (52.4%) and azathioprine (47.0%). Step-up strategy was preferred in mild-moderate UC (96.4%), while 51.8% of the physicians selected top-down treatment for CD. Only 25.9% and 17.5% of the physicians could test blood concentration of infliximab and antibody to infliximab in their hospitals, respectively. Conclusions The current status of drug therapy and monitoring for IBD in Asia possesses commonalities as well as differences. Asian recommendations, IBD specialist teams and practice of therapeutic drug monitoring are required to improve IBD management in Asia.
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Ferretti F, Cannatelli R, Monico MC, Maconi G, Ardizzone S. An Update on Current Pharmacotherapeutic Options for the Treatment of Ulcerative Colitis. J Clin Med 2022; 11:jcm11092302. [PMID: 35566428 PMCID: PMC9104748 DOI: 10.3390/jcm11092302] [Citation(s) in RCA: 49] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2022] [Revised: 04/10/2022] [Accepted: 04/18/2022] [Indexed: 12/17/2022] Open
Abstract
The main goals of Ulcerative Colitis (UC) treatment are to both induce and maintain the clinical and endoscopic remission of disease, reduce the incidence of complications such as dysplasia and colorectal carcinoma and improve quality of life. Although a curative medical treatment for UC has not yet been found, new therapeutic strategies addressing specific pathogenetic mechanisms of disease are emerging. Notwithstanding these novel therapies, non-biological conventional drugs remain a mainstay of treatment. The aim of this review is to summarize current therapeutic strategies used as treatment for ulcerative colitis and to briefly focus on emerging therapeutic strategies, including novel biologic therapies and small molecules. To date, multiple therapeutic approaches can be adopted in UC and the range of available compounds is constantly increasing. In this era, the realization of well-designed comparative clinical trials, as well as the definition of specific therapeutic models, would be strongly suggested in order to achieve personalized management for UC patients.
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Majumder S, Shivaji UN, Kasturi R, Sigamani A, Ghosh S, Iacucci M. Inflammatory bowel disease-related colorectal cancer: Past, present and future perspectives. World J Gastrointest Oncol 2022; 14:547-567. [PMID: 35321275 PMCID: PMC8919014 DOI: 10.4251/wjgo.v14.i3.547] [Citation(s) in RCA: 22] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2021] [Revised: 04/21/2021] [Accepted: 02/27/2022] [Indexed: 02/06/2023] Open
Abstract
Inflammatory bowel disease-related colorectal cancer (IBD-CRC) is one of the most serious complications of IBD contributing to significant mortality in this cohort of patients. IBD is often associated with diet and lifestyle-related gut microbial dysbiosis, the interaction of genetic and environmental factors, leading to chronic gut inflammation. According to the “common ground hypothesis”, microbial dysbiosis and intestinal barrier impairment are at the core of the chronic inflammatory process associated with IBD-CRC. Among the many underlying factors known to increase the risk of IBD-CRC, perhaps the most important factor is chronic persistent inflammation. The persistent inflammation in the colon results in increased proliferation of cells necessary for repair but this also increases the risk of dysplastic changes due to chromosomal and microsatellite instability. Multiple pathways have been identified, regulated by many positive and negative factors involved in the development of cancer, which in this case follows the ‘inflammation-dysplasia-carcinoma’ sequence. Strategies to lower this risk are extremely important to reduce morbidity and mortality due to IBD-CRC, among which colonoscopic surveillance is the most widely accepted and implemented modality, forming part of many national and international guidelines. However, the effectiveness of surveillance in IBD has been a topic of much debate in recent years for multiple reasons — cost-benefit to health systems, resource requirements, and also because of studies showing conflicting long-term data. Our review provides a comprehensive overview of past, present, and future perspectives of IBD-CRC. We explore and analyse evidence from studies over decades and current best practices followed globally. In the future directions section, we cover emerging novel endoscopic techniques and artificial intelligence that could play an important role in managing the risk of IBD-CRC.
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Affiliation(s)
- Snehali Majumder
- Department of Clinical Research, Narayana Health, Bangalore 560099, Karnataka, India
| | - Uday Nagesh Shivaji
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, United Kingdom
| | - Rangarajan Kasturi
- Department of Gastroenterology, Narayana Health, Bangalore 560099, India
| | - Alben Sigamani
- Department of Clinical Research, Narayana Health, Bangalore 560099, Karnataka, India
| | - Subrata Ghosh
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, United Kingdom
| | - Marietta Iacucci
- National Institute for Health Research Birmingham Biomedical Research Centre, University Hospitals Birmingham, Birmingham B15 2TH, United Kingdom
- Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TH, United Kingdom
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Abstract
Most patients with colorectal cancer (CRC) were diagnosed in advanced stage and the prognosis is poor. Therefore, early detection and prevention of CRC are very important. As with other cancers, there is also the tertiary prevention for CRC. The primary prevention is etiological prevention, which is mainly the treatment of adenoma or inflammation for preventing the development into cancer. The secondary prevention is the early diagnosis and early treatment for avoiding progressing to advanced cancer. The tertiary prevention belongs to the broad category of prevention, mainly for advanced CRC, through surgical treatment and postoperative adjuvant chemotherapy, radiotherapy, targeted therapy, immunotherapy for preventing tumor recurrence or metastasis. This consensus is based on the recent domestic and international consensus guidelines and the latest progress of international researches in the past five years. This consensus opinion seminar was hosted by the Chinese Society of Gastroenterology and Cancer Collaboration Group of Chinese Society of Gastroenterology, and was organized by the Division of Gastroenterology and Hepatology & Shanghai Institute of Digestive Disease, Renji Hospital, School of Medicine, Shanghai Jiao Tong University. The consensus opinion contains 60 statement clauses, the standard and basis of the evidence-based medicine grade and voting grade of the statement strictly complied with the relevant international regulations and practice.
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Ranasinghe R, Mathai M, Zulli A. A synopsis of modern - day colorectal cancer: Where we stand. Biochim Biophys Acta Rev Cancer 2022; 1877:188699. [DOI: 10.1016/j.bbcan.2022.188699] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2021] [Revised: 01/30/2022] [Accepted: 02/14/2022] [Indexed: 02/07/2023]
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Olegovich Bokov D, Jalil AT, Alsultany FH, Mahmoud MZ, Suksatan W, Chupradit S, Qasim MT, Delir Kheirollahi Nezhad P. Ir-decorated gallium nitride nanotubes as a chemical sensor for recognition of mesalamine drug: a DFT study. MOLECULAR SIMULATION 2022. [DOI: 10.1080/08927022.2021.2025234] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/01/2023]
Affiliation(s)
- Dmitry Olegovich Bokov
- Institute of Pharmacy, Sechenov First Moscow State Medical University, Moscow, Russian Federation
- Laboratory of Food Chemistry, Federal Research Center of Nutrition, Biotechnology and Food Safety, Moscow, Russian Federation
| | - Abduladheem Turki Jalil
- Faculty of Biology and Ecology, Yanka Kupala State University of Grodno, Grodno, Belarus
- College of Technical Engineering, The Islamic University, Najaf, Iraq
- Department of Dentistry, Kut University College, Kut, Iraq
| | - Forat H. Alsultany
- Medical Physics Department, Al-Mustaqbal University College, Hillah, Iraq
| | - Mustafa Z. Mahmoud
- Department of Radiology and Medical Imaging, College of Applied Medical Sciences, Prince Sattam bin Abdulaziz University, Al-Kharj, Saudi Arabia
- Faculty of Health, University of Canberra, Canberra, Australia
| | - Wanich Suksatan
- Faculty of Nursing, HRH Princess Chulabhorn College of Medical Science, Chulabhorn Royal Academy, Bangkok, Thailand
| | - Supat Chupradit
- Faculty of Associated Medical Sciences, Department of Occupational Therapy, Chiang Mai University, Chiang Mai, Thailand
| | - Maytham T. Qasim
- Ministry of Education, Directorate Thi-Qar Education, Thi-Qar, Iraq
- Department of Anesthesia, College of Health and Medical Technololgy, Al-Ayen University, Thi-Qar, Iraq
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Yang H, Jiang Z, Liu L, Zeng Y, Ebadi AG. A DFT study on the Pd-decorated AlP quantum dots as chemical sensor for recognition of mesalamine drug. PHOSPHORUS SULFUR 2022. [DOI: 10.1080/10426507.2021.2013843] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Affiliation(s)
- Hongmei Yang
- College of Chemical Engineering and Resource Reuse, Wuzhou University, Wuzhou, Guangxi, China
| | - Zheng Jiang
- College of Chemical Engineering and Resource Reuse, Wuzhou University, Wuzhou, Guangxi, China
| | - Lingling Liu
- College of Chemical Engineering and Resource Reuse, Wuzhou University, Wuzhou, Guangxi, China
| | - Yanyun Zeng
- College of Chemical Engineering and Resource Reuse, Wuzhou University, Wuzhou, Guangxi, China
| | - Abdol Ghaffar Ebadi
- Department of Agriculture, Jouybar Branch, Islamic Azad University, Jouybar, Iran
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Herfarth H, Vavricka SR. 5-Aminosalicylic Acid Chemoprevention in Inflammatory Bowel Diseases: Is It Necessary in the Age of Biologics and Small Molecules? Inflamm Intest Dis 2022; 7:28-35. [PMID: 35224015 PMCID: PMC8820128 DOI: 10.1159/000518865] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2021] [Accepted: 08/03/2021] [Indexed: 11/01/2023] Open
Abstract
BACKGROUND Due to the increased incidence of colorectal cancer in inflammatory bowel diseases (IBDs), the value of chemoprevention for this patient group has been repeatedly debated in the past decade. This review describes available evidence and the current recommendations for chemoprevention in national and international guidelines IBD guidelines. SUMMARY 5-Aminosalicylic acid (5-ASA) compounds are the preferred therapeutic option for mild to moderate ulcerative colitis (UC). Aside from the known anti-inflammatory effects, their chemopreventive abilities have been described in vitro and in vivo. Pooling the increasing number of retrospective and population-based clinical studies over the last 15 years, 7 consecutive meta-analyses revealed partially conflicting results for the chemopreventive efficacy of 5-ASA, and thus, not all IBD guidelines currently recommend chemoprevention with mesalamine compounds. Accumulating evidence for decreasing the colorectal cancer (CRC) risk in support of thiopurines more recently shows a protective effect. This effect seems solely mediated by control of intestinal inflammation since, for this drug class, another mechanistic interference in IBD-associated CRC pathogenesis is not known. The results regarding chemopreventive efficacy for ursodeoxycholic acid or folic acid are equivocal, and the use of these medications to prevent CRC is not firmly established. Like UC, the risk of CRC is also significantly increased in patients with Crohn's disease (CD), especially Crohn's colitis. However, no published studies exclusively assess the effects of surveillance on the early detection of cancer or CRC chemoprevention in CD patients. In meta-analyses, which predominantly included UC patients, 5-ASA or thiopurines were not beneficial in small CD subgroups. The level of evidence for anti-TNFα agents, anti-integrin (e.g., vedolizumab), or anti-IL-12/IL-23 agents (e.g., ustekinumab) and Janus kinase inhibitors is currently too low or nonexistent to use them solely for chemoprevention in UC or CD patients. KEY MESSAGE Intestinal inflammation is one of the main risk factors for developing CRC in IBD, and all drugs that induce and maintain mucosal healing most likely also decrease the IBD-associated CRC risk. Thus, a therapeutic strategy of adding a 5-ASA therapy to a successfully mucosal healing-inducing therapy, for example, with a biologic or a small molecule merely to prevent CRC appears to be obsolete.
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Affiliation(s)
- Hans Herfarth
- Division of Gastroenterology and Hepatology, University of North Carolina, Chapel Hill, North Carolina, USA
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Wan J, Wang X, Zhang Y, Xue X, Jia H, Wang M, Liang J, Wu K. OUP accepted manuscript. Gastroenterol Rep (Oxf) 2022; 10:goac019. [PMID: 35599745 PMCID: PMC9114755 DOI: 10.1093/gastro/goac019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2022] [Revised: 03/31/2022] [Accepted: 04/06/2022] [Indexed: 11/17/2022] Open
Abstract
Background Ulcerative colitis (UC) is a chronic lifelong disease. The disease extent of UC can progress over time. This study aimed to assess whether cumulative inflammatory burden (CIB) is associated with disease extension in distal UC (proctitis [E1] and left-sided colitis [E2]) patients, and to develop a quantified indicator of CIB. Methods In this retrospective study based on a prospective registry, distal UC patients receiving colonoscopies in Xijing Hospital (Xi’an, China) from January 2000 to May 2019 were studied. We developed a new score, namely the time-adjusted average Mayo endoscopic score (TA-MES), calculated as dividing the sum of the cumulative average MES over a period of surveillance time by the length of the endoscopic examination interval, to quantify the CIB. Cox regression was used to identify other potential risk factors. Results A total of 295 UC patients were followed for 1,487.02 patient-years. Among them, 140 patients (47.5%) experienced disease extension. Multivariate analysis showed that the TA-MES was significantly associated with disease extension in E1 (hazard ratio [HR], 2.90; 95% confidence interval [CI], 1.58–5.33, P = 0.001) and E2 (HR, 1.89; 95% CI, 1.16–3.09, P = 0.011) patients. Other risk factors included hemoglobin of <90 g/L and appendiceal skip inflammation; the protective factors included age, E2 at diagnosis, former smoking, and 5-aminosalicylic acid dose. Otherwise, MES at diagnosis, maximal MES, and mean MES failed to estimate the risk of disease extension. Conclusion TA-MES is a good quantified indicator of CIB and is independently associated with increased disease extension in distal UC patients. Whether the dynamic multiple scoring system could be used as a risk factor in other chronic relapsing–remitting diseases is a direction for future research.
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Affiliation(s)
- Jian Wan
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi, P. R. China
| | - Xuan Wang
- Department of Neurology, Xijing Hospital, Fourth Military Medical University, Xi’an, Shaanxi, P. R. China
| | - Yujie Zhang
- Department of Histology and Embryology, School of Basic Medicine, Xi’an Medical University, Xi’an, Shaanxi, P. R. China
| | - Xianmin Xue
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi, P. R. China
| | - Hui Jia
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi, P. R. China
| | - Min Wang
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi, P. R. China
| | - Jie Liang
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi, P. R. China
| | - Kaichun Wu
- State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an, Shaanxi, P. R. China
- Corresponding author. Xijing Hospital of Digestive Diseases, Fourth Military Medical University, 127 Changle West Road, Xi’an, Shaanxi 710032, P. R. China. Tel: +86-29-84771502; Fax: +86-29-82539041;
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Porter RJ, Arends MJ, Churchhouse AMD, Din S. Inflammatory Bowel Disease-Associated Colorectal Cancer: Translational Risks from Mechanisms to Medicines. J Crohns Colitis 2021; 15:2131-2141. [PMID: 34111282 PMCID: PMC8684457 DOI: 10.1093/ecco-jcc/jjab102] [Citation(s) in RCA: 74] [Impact Index Per Article: 18.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
The cumulative impact of chronic inflammation in patients with inflammatory bowel diseases predisposes to the development of inflammatory bowel disease-associated colorectal cancer [IBD-CRC]. Inflammation can induce mutagenesis, and the relapsing-remitting nature of this inflammation, together with epithelial regeneration, may exert selective pressure accelerating carcinogenesis. The molecular pathogenesis of IBD-CRC, termed the 'inflammation-dysplasia-carcinoma' sequence, is well described. However, the immunopathogenesis of IBD-CRC is less well understood. The impact of novel immunosuppressive therapies, which aim to achieve deep remission, is mostly unknown. Therefore, this timely review summarizes the clinical context of IBD-CRC, outlines the molecular and immunological basis of disease pathogenesis, and considers the impact of novel biological therapies.
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Affiliation(s)
- Ross J Porter
- Centre for Inflammation Research, Queen’s Medical Research Institute, University of Edinburgh, UK
- NHS Lothian Edinburgh IBD Unit, Western General Hospital, UK
| | - Mark J Arends
- Division of Pathology, Cancer Research UK Edinburgh Centre, Institute of Cancer & Genetics, Western General Hospital, University of Edinburgh, UK
| | | | - Shahida Din
- NHS Lothian Edinburgh IBD Unit, Western General Hospital, UK
- Corresponding author: Dr Shahida Din, Edinburgh IBD Unit, Anne Ferguson Building, Western General Hospital, Edinburgh EH4 2XU, UK. Tel: +44 (0) 131 537 1758;
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Tang-Fichaux M, Branchu P, Nougayrède JP, Oswald E. Tackling the Threat of Cancer Due to Pathobionts Producing Colibactin: Is Mesalamine the Magic Bullet? Toxins (Basel) 2021; 13:toxins13120897. [PMID: 34941734 PMCID: PMC8703417 DOI: 10.3390/toxins13120897] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2021] [Revised: 12/01/2021] [Accepted: 12/08/2021] [Indexed: 12/15/2022] Open
Abstract
Colibactin is a genotoxin produced primarily by Escherichia coli harboring the genomic pks island (pks+ E. coli). Pks+ E. coli cause host cell DNA damage, leading to chromosomal instability and gene mutations. The signature of colibactin-induced mutations has been described and found in human colorectal cancer (CRC) genomes. An inflamed intestinal environment drives the expansion of pks+ E. coli and promotes tumorigenesis. Mesalamine (i.e., 5-aminosalycilic acid), an effective anti-inflammatory drug, is an inhibitor of the bacterial polyphosphate kinase (PPK). This drug not only inhibits the production of intestinal inflammatory mediators and the proliferation of CRC cells, but also limits the abundance of E. coli in the gut microbiota and diminishes the production of colibactin. Here, we describe the link between intestinal inflammation and colorectal cancer induced by pks+ E. coli. We discuss the potential mechanisms of the pleiotropic role of mesalamine in treating both inflammatory bowel diseases and reducing the risk of CRC due to pks+ E. coli.
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Affiliation(s)
- Min Tang-Fichaux
- IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, 31024 Toulouse, France; (M.T.-F.); (P.B.); (J.-P.N.)
| | - Priscilla Branchu
- IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, 31024 Toulouse, France; (M.T.-F.); (P.B.); (J.-P.N.)
| | - Jean-Philippe Nougayrède
- IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, 31024 Toulouse, France; (M.T.-F.); (P.B.); (J.-P.N.)
| | - Eric Oswald
- IRSD, Université de Toulouse, INSERM, INRAE, ENVT, UPS, 31024 Toulouse, France; (M.T.-F.); (P.B.); (J.-P.N.)
- Service de Bactériology-Hygiène, Hôpital Purpan, CHU de Toulouse, 31059 Toulouse, France
- Correspondence:
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Lucafò M, Curci D, Franzin M, Decorti G, Stocco G. Inflammatory Bowel Disease and Risk of Colorectal Cancer: An Overview From Pathophysiology to Pharmacological Prevention. Front Pharmacol 2021; 12:772101. [PMID: 34744751 PMCID: PMC8563785 DOI: 10.3389/fphar.2021.772101] [Citation(s) in RCA: 64] [Impact Index Per Article: 16.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 10/06/2021] [Indexed: 12/14/2022] Open
Abstract
Increased risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) patients has been attributed to long-standing chronic inflammation, with the contribution of genetic alterations and environmental factors such as the microbiota. Moreover, accumulating data indicate that IBD-associated CRC (IBD-CRC) may initiate and develop through a pathway of tumorigenesis distinct from that of sporadic CRC. This mini-review summarizes the current knowledge of IBD-CRC, focusing on the main mechanisms underlying its pathogenesis, and on the important role of immunomodulators and biologics used to treat IBD patients in interfering with the inflammatory process involved in carcinogenesis.
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Affiliation(s)
- Marianna Lucafò
- Institute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy
| | - Debora Curci
- Institute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy
| | - Martina Franzin
- Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
| | - Giuliana Decorti
- Institute for Maternal and Child Health-IRCCS Burlo Garofolo, Trieste, Italy.,Department of Medical, Surgical and Health Sciences, University of Trieste, Trieste, Italy
| | - Gabriele Stocco
- Department of Life Sciences, University of Trieste, Trieste, Italy
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Ali Bilici, Çogal Y, Geçibesler İH, Kaya İ. Enzyme Catalyzed Synthesis of Water Soluble Mesalazine Oligomers and Evaluation of their Efficiency in Polypropylene Stabilization. POLYMER SCIENCE SERIES B 2021. [DOI: 10.1134/s1560090421060051] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/23/2022]
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Choi YY, Lee JK, Kim HS, Kim DW, Kim HM, Kang DR. Medications and the Risk of Colorectal Cancer in Patients with Inflammatory Bowel Diseases: Use of the Landmark Method. Yonsei Med J 2021; 62:997-1004. [PMID: 34672133 PMCID: PMC8542472 DOI: 10.3349/ymj.2021.62.11.997] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2021] [Revised: 08/02/2021] [Accepted: 08/09/2021] [Indexed: 12/30/2022] Open
Abstract
PURPOSE This study aimed to determine whether the use of drugs in the treatment of inflammatory bowel disease is related to the risk of colorectal cancer using a Cox proportional hazards model with the landmark method to minimize immortal time bias. MATERIALS AND METHODS This study was conducted as national cohort-based study using data from Korea's Health Insurance Corporation. Newly diagnosed patients with inflammatory bowel disease from 2006 to 2010 were monitored for colorectal cancer until 2015. Hazard ratios and 95% confidence intervals were calculated and compared with the incidence of colorectal cancer with or without medications by applying various landmark points. RESULTS In patients with Crohn's disease, the prevention of colorectal cancer in the group exposed to immunomodulators was significant in the basic Cox model; however, the effect was not statistically significant in the model using the landmark method. The preventive effect of 5-aminosalicylic acid in patients with ulcerative colitis was significant in the basic and 6-month landmark point application models, but not in the remaining landmark application models. CONCLUSION In patients with inflammatory bowel disease, the preventive effect of drug exposure on colorectal cancer varies depending on the application of the landmark method. Hence, the possibility of immortal time bias should be considered.
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Affiliation(s)
- Yoon Young Choi
- Artificial Intelligence Big Data Medical Center, Wonju College of Medicine, Yonsei University, Wonju, Korea
| | - Jung Kuk Lee
- Department of Biostatistics, Wonju College of Medicine, Yonsei University, Wonju, Korea
| | - Hyun-Soo Kim
- Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju, Korea
| | - Dong Wook Kim
- Department of Information and Statistics, Gyeongsang National University, Jinju, Korea
| | - Hee Man Kim
- Department of Internal Medicine, Wonju College of Medicine, Yonsei University, Wonju, Korea
| | - Dae Ryong Kang
- Department of Biostatistics, Wonju College of Medicine, Yonsei University, Wonju, Korea
- Department of Precision Medicine, Wonju College of Medicine, Yonsei University, Wonju, Korea.
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Wijnands AM, Mahmoud R, Lutgens MWMD, Oldenburg B. Surveillance and management of colorectal dysplasia and cancer in inflammatory bowel disease: Current practice and future perspectives. Eur J Intern Med 2021; 93:35-41. [PMID: 34481721 DOI: 10.1016/j.ejim.2021.08.010] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/04/2021] [Revised: 08/10/2021] [Accepted: 08/12/2021] [Indexed: 12/30/2022]
Abstract
Patients with inflammatory bowel disease (IBD) are at increased risk of developing colorectal cancer (CRC). Current guidelines recommend frequent surveillance colonoscopies for patients with at least left-sided ulcerative colitis, or Crohn's disease involving more than 30% of the colon. Surveillance allows for early detection and treatment of colorectal dysplasia and cancer. The first colonoscopy should be performed 8 to 10 years after onset of disease symptoms. European and British guidelines employ a risk-stratification algorithm that assigns patients to surveillance intervals of one, three or five years, whereas American guidelines recommend to perform surveillance every 1 to 3 years based on the (combined) presence of risk factors. Patients with concomitant primary sclerosing cholangitis are at an additionally increased risk, and should undergo annual surveillance starting immediately after the diagnosis. The current practice of surveillance is based on limited evidence, is resource intensive and cannot preclude the occurrence of interval carcinomas. Fortunately, advances in endoscopic techniques for mucosal visualisation, along with better control of inflammation, have resulted in a declining incidence of CRC in patients with IBD. Furthermore, advanced endoscopic resection techniques can be expected to result in a shift from surgical to endoscopic management of dysplastic lesions. In this review, we provide an up-to-date overview of colitis-associated CRC pathophysiology, epidemiology, surveillance practices, and management of dysplasia.
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Affiliation(s)
- Anouk M Wijnands
- Inflammatory Bowel Disease Centre, Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, the Netherlands
| | - Remi Mahmoud
- Inflammatory Bowel Disease Centre, Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, the Netherlands
| | - Maurice W M D Lutgens
- Department of Gastroenterology and Hepatology, Elisabeth-TweeSteden Hospital, Tilburg, the Netherlands
| | - Bas Oldenburg
- Inflammatory Bowel Disease Centre, Department of Gastroenterology and Hepatology, University Medical Centre Utrecht, Utrecht, the Netherlands.
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