|
1
|
Yao X, Chen Y, Li Y, Mo J, Liu X, Wang P, Jia D, Li H, Guo C. Chrysin ameliorates dextran sulfate-induced ulcerative colitis in mice by modulating inflammation and gut microbiota. Int J Colorectal Dis 2025; 40:57. [PMID: 40035853 PMCID: PMC11880046 DOI: 10.1007/s00384-025-04843-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/17/2025] [Indexed: 03/06/2025]
Abstract
BACKGROUND Inflammatory bowel disease (IBD) encompasses chronic inflammation of the colon and rectum, posing significant health challenges. Previous studies have shown potential therapeutic effects of natural compounds on IBD. Chrysin, a naturally occurring flavonoid, has been suggested to modulate inflammatory pathways and gut microbiota, but its comprehensive impact on ulcerative colitis remains inadequately explored. METHODS This study employed a dextran sulfate sodium (DSS)-induced ulcerative colitis model in mice to investigate the effects of Chrysin. Using network pharmacology, we identified key signaling pathways potentially influenced by Chrysin. Experimental approaches included measuring disease activity index scores, serum levels of TNF-α, and assessing colon damage histologically. Transcriptomic and microbiome analyses were conducted to examine changes in gene expression and gut bacterial populations, respectively. Additionally, metabolomic profiling was used to identify alterations in colon metabolites. RESULTS Chrysin treatment significantly mitigated weight loss and reduced disease activity index scores in DSS-induced mice. There was a notable decrease in serum TNF-α levels and less histological damage in the colon. Transcriptomic analysis revealed significant alterations in gene expression within the NF-κB and IL-17 signaling pathways. Microbiome analysis showed significant shifts in the populations of Bacteroidetes and Firmicutes. Metabolomics analysis identified changes in 298 colon metabolites, implicating several essential metabolic pathways. CONCLUSIONS The findings suggest that Chrysin exerts a dual-action therapeutic effect on ulcerative colitis by reducing inflammation and modulating the gut microbiota. These multifaceted impacts highlight Chrysin's potential utility as a novel therapeutic agent in the clinical management of IBD, offering valuable insights into its mechanisms of action and paving the way for future clinical trials.
Collapse
Affiliation(s)
- Xin Yao
- Affiliated Banan Hospital of Chongqing Medical University, Long Zhou Wan Street, Yunan District, Chongqing, 401320, China
| | - Yao Chen
- Affiliated Banan Hospital of Chongqing Medical University, Long Zhou Wan Street, Yunan District, Chongqing, 401320, China
| | - Yang Li
- Affiliated Banan Hospital of Chongqing Medical University, Long Zhou Wan Street, Yunan District, Chongqing, 401320, China
| | - Jieyu Mo
- Affiliated Banan Hospital of Chongqing Medical University, Long Zhou Wan Street, Yunan District, Chongqing, 401320, China
| | - Xia Liu
- Affiliated Banan Hospital of Chongqing Medical University, Long Zhou Wan Street, Yunan District, Chongqing, 401320, China
| | - Peng Wang
- Xinqiao Hospital, Army Medical University, No.183 Xinqiao Road, Chongqing, 400037, China
| | - Daqi Jia
- Affiliated Banan Hospital of Chongqing Medical University, Long Zhou Wan Street, Yunan District, Chongqing, 401320, China.
| | - Huaqiang Li
- Affiliated Banan Hospital of Chongqing Medical University, Long Zhou Wan Street, Yunan District, Chongqing, 401320, China.
| | - Chunfang Guo
- Affiliated Banan Hospital of Chongqing Medical University, Long Zhou Wan Street, Yunan District, Chongqing, 401320, China.
| |
Collapse
|
|
2
|
Khalifa A, Alkuwayti MA, Abdallah BM, Ali EM, Ibrahim HIM. Probiotic and Rice-Derived Compound Combination Mitigates Colitis Severity. Pharmaceuticals (Basel) 2024; 17:1463. [PMID: 39598375 PMCID: PMC11597685 DOI: 10.3390/ph17111463] [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: 08/24/2024] [Revised: 10/07/2024] [Accepted: 10/30/2024] [Indexed: 11/29/2024] Open
Abstract
BACKGROUND This study investigated the ability of Enterococcus lactis (E. lactis) and Hasawi rice protein lysate (HPL) to suppress colitis induced by dextran sulfate sodium (DSS) in miceColitis is characterized by inflammation of the colon, and exploring potential therapeutic agents could lead to improved management strategies. METHODS Male mice were subjected to DSS treatment to induce colitis, followed by supplementation with E. lactis and/or HPL. The study assessed various parameters, including disease activity index (DAI) scores, gut permeability measured using FITC-dextran, and superoxide dismutase (SOD) activity in excised colon tissues from both treated and untreated control groups. RESULTS E. lactis supplementation significantly alleviated DSS-induced colitis, as evidenced by improved DAI scores and enhanced gut permeability. Notably, E. lactis combined with HPL (0.1 mg/108) exhibited superior tolerance to a 0.5% pancreatin solution compared to E. lactis alone. Both E. lactis and the combination treatment significantly increased SOD activity (5.6 ± 0.23 SOD U/mg protein for E. lactis and 6.7 ± 0.23 SOD U/mg protein for the combination) relative to the Azoxymethane (AOM)/DSS group, suggesting a reduction in oxidative stress. Additionally, pro-inflammatory markers were significantly reduced in the group receiving both E. lactis and HPL compared to the E. lactis-only group. Levels of proteins associated with cell death, such as PCNA, PTEN, VEGF, COX-2, and STAT-3, were significantly decreased by 14.8% to 80% following E. lactis supplementation, with the combination treatment showing the most pronounced effects. CONCLUSIONS These findings suggest E. lactis supplementation may be beneficial for colitis, with HPL potential to enhance its effectiveness.
Collapse
Affiliation(s)
- Ashraf Khalifa
- Biological Science Department, College of Science, King Faisal University, P.O. Box 400, Al-Ahsa 31982, Saudi Arabia
- Botany and Microbiology Department, Faculty of Science, Beni-Suef University, Beni-Suef 62511, Egypt
| | - Mayyadah Abdullah Alkuwayti
- Biological Science Department, College of Science, King Faisal University, P.O. Box 400, Al-Ahsa 31982, Saudi Arabia
| | - Basem M. Abdallah
- Biological Science Department, College of Science, King Faisal University, P.O. Box 400, Al-Ahsa 31982, Saudi Arabia
| | - Enas M. Ali
- Biological Science Department, College of Science, King Faisal University, P.O. Box 400, Al-Ahsa 31982, Saudi Arabia
| | - Hairul Islam M. Ibrahim
- Biological Science Department, College of Science, King Faisal University, P.O. Box 400, Al-Ahsa 31982, Saudi Arabia
- Molecular Biology Division, Pondicherry Centre for Biological Sciences and Educational Trust, Pondicherry 605004, India
| |
Collapse
|
|
3
|
D'Amico F, Magro F, Dignass A, Al Awadhi S, Gutierrez Casbas A, Queiroz NSF, Rydzewska G, Duk Ye B, Ran Z, Hart A, Jairath V, Fiorino G, Peyrin-Biroulet L, Danese S. Practical management of mild-to-moderate ulcerative colitis: an international expert consensus. Expert Rev Gastroenterol Hepatol 2024; 18:421-430. [PMID: 39225555 DOI: 10.1080/17474124.2024.2397650] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/01/2024] [Accepted: 08/24/2024] [Indexed: 09/04/2024]
Abstract
INTRODUCTION Although there are well-defined guidelines for the management of mild-to-moderate ulcerative colitis (UC), there are still unmet needs. For this reason, we conducted an international expert consensus to standardize the management of patients with mild-to-moderate UC and provide practical guidance to clinicians. AREAS COVERED Based on Delphi methodology, 15 statements were approved after two rounds of voting, addressing several aspects of disease management from sequencing to treatment duration, from monitoring to optimization techniques and safety profile. EXPERT OPINION Growing knowledge of mild-to-moderate UC has led to the development of new ambitious outcomes such as histological remission and disease clearance. Furthermore, noninvasive tools for patient monitoring such as fecal calprotectin and intestinal ultrasound are now available. Their implementation in clinical practice will allow clinicians to tightly monitor disease activity and promptly adapt treatment, avoiding complications and disease progression and targeting better disease control.
Collapse
Affiliation(s)
- Ferdinando D'Amico
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
| | - Fernando Magro
- CINTESIS@RISE, Faculty of Medicine, The University of Porto, Porto, Portugal
| | - Axel Dignass
- Department of Medicine I, Agaplesion Markus Hospital, Goethe University, Frankfurt/Main, Germany
| | | | - Ana Gutierrez Casbas
- Department of Gastroenterology, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas (CIBERehd), Madrid, España
- Department of Gastroenterology, Hospital General Universitario de Alicante, Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL), Alicante, España
| | | | - Grażyna Rydzewska
- Department of Gastroenterology and Internal Medicine, National Medical Institute of Ministry of Interior and Administration, Warsaw, Poland
| | - Byong Duk Ye
- Department of Gastroenterology and Inflammatory Bowel Disease Center, AsanMedical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea
| | - Zhihua Ran
- Department of Gastroenterology Zhou Pu Hospital, Shanghai University of Medicine & Health Sciences, Shanghai, China
| | - Ailsa Hart
- Inflammatory Bowel Disease Unit, St Mark's Hospital, London, UK
| | - Vipul Jairath
- Departments of Gastroenterology and Medicine, Western University Schulich School of Medicine & Dentistry, London, Ontario, Canada
| | - Gionata Fiorino
- IBD Unit, Department of Gastroenterology and Digestive Endoscopy, San Camillo-Forlanini Hospital, Rome, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- Department of Gastroenterology, Inserm, NGERE, University of Lorraine, Nancy, France
- Department of Gastroenterology, INFINY Institute, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- Department of Gastroenterology, FHU-CURE, Nancy University Hospital, Vandœuvre-lès-Nancy, France
- Department of Gastroenterology, Groupe Hospitalier privé Ambroise Paré - Hartmann, Paris IBD center, Neuilly sur Seine, France
- Department of Gastroenterology, Division of Gastroenterology and Hepatology, McGill University Health Centre, Montreal, QC, Canada
| | - Silvio Danese
- Gastroenterology and Endoscopy, IRCCS San Raffaele Hospital, Milan, Italy
- Gastroenterology and Endoscopy, Vita-Salute San Raffaele University, Milan, Italy
| |
Collapse
|
|
4
|
Mark-Christensen A, Kristiansen EB, Myrelid P, Laurberg S, Erichsen R. Appendectomy and Risk of Advanced Colorectal Neoplasia in Inflammatory Bowel Disease: A Nationwide Population-based Cohort Study. Inflamm Bowel Dis 2024; 30:877-883. [PMID: 37523678 DOI: 10.1093/ibd/izad141] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/23/2023] [Indexed: 08/02/2023]
Abstract
BACKGROUND The aim of this study was to examine the association between appendectomy and advanced colorectal neoplasia (aCRN) in patients with inflammatory bowel disease (IBD). METHODS Inflammatory bowel disease patients diagnosed in Denmark in the period 1977 to 2017 were identified from the Danish National Patient Registry. Inflammatory bowel disease patients who underwent appendectomy were matched with up to 10 IBD patients without appendectomy and followed until aCRN, death, or emigration. Absolute risks of aCRN were calculated, treating death and bowel resections as competing risks. Stratified Cox regression was used to calculate adjusted hazard ratios (aHRs) of aCRN, comparing IBD patients with appendectomy to IBD patients without appendectomy. RESULTS We identified 3789 IBD patients with appendectomy and 37 676 IBD patients without appendectomy. A total of 573 patients (1.4%) developed aCRN, with an absolute risk of aCRN at 20 years of 4.9% (95% confidence interval [CI], 2.9%-7.7%) for ulcerative colitis (UC) patients with appendectomy after UC diagnosis compared with 2.8% (95% CI, 2.3%-3.3%) for UC patients without appendectomy. Appendectomy after UC was associated with an increased rate of aCRN 5 to 10 years (aHR, 2.5; 95% CI, 1.1-5.5) and 10 to 20 years after appendectomy (aHR, 2.3; 95% CI, 1.0-5.5). Appendectomy prior to UC diagnosis was not associated with an increased rate of aCRN, and Crohn's disease was not associated with the rate of aCRN, regardless of timing or histological diagnosis of the appendix specimen. CONCLUSIONS Although appendectomy may have a positive effect on the clinical course of UC, our study suggests that this may come at the expense of a higher risk of aCRN.
Collapse
Affiliation(s)
- Anders Mark-Christensen
- Department of Clinical Epidemiology, Aarhus University Hospital, Denmark
- Department of Surgery, Svendborg Hospital OUH, Denmark
| | | | - Pär Myrelid
- Department of Surgery, Linköping University Hospital, Linköping, Sweden
- Department of Biomedical and Clinical Sciences, Division of Surgery, Linköping University, Linköping, Sweden
| | - Søren Laurberg
- Department of Surgery, Aarhus University Hospital, Aarhus, Denmark
| | - Rune Erichsen
- Department of Clinical Epidemiology, Aarhus University Hospital, Denmark
- Department of Surgery, Randers Regional Hospital, Randers, Denmark
| |
Collapse
|
|
5
|
Ungaro RC, Kadali H, Zhang W, Adsul S, Reinisch W. Impact of Concomitant 5-Aminosalicylic Acid Therapy on Vedolizumab Efficacy and Safety in Inflammatory Bowel Disease: Post Hoc Analyses of Clinical Trial Data. J Crohns Colitis 2023; 17:1949-1961. [PMID: 37492976 PMCID: PMC10798864 DOI: 10.1093/ecco-jcc/jjad113] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Indexed: 07/27/2023]
Abstract
BACKGROUND AND AIMS The benefit of continuing 5-aminosalicylic acid [5-ASA] treatment when escalating to advanced therapies in patients with inflammatory bowel disease [IBD] is unclear. Vedolizumab is a gut-selective monoclonal anti-α4β7-integrin antibody used to treat moderate to severe IBD. Clinical trial data were analysed post hoc to assess the impact of 5-ASA co-treatment on vedolizumab efficacy and safety in patients with IBD. METHODS Data were analysed from patients aged 18-80 years with moderate to severe ulcerative colitis [UC]/Crohn's disease [CD] receiving intravenous [IV]/subcutaneous [SC] vedolizumab. Efficacy data were from four studies [GEMINI 1 and 2 and VISIBLE 1 and 2]; safety data were from seven studies [GEMINI 1‒3 and long-term, VISIBLE 1, 2, and open-label extension]. The impact of 5-ASA co-treatment on clinical and endoscopic outcomes at Weeks 6 and 52 was assessed using multivariate analysis (adjusted odds ratios [aORs] with 95% confidence intervals [CIs]). RESULTS There were no significant differences in UC clinical remission [Mayo score ≤2, no subscore >1] rates with vs without 5-ASA at Week 6 [20.7% vs 20.4%, respectively; aOR 0.77, 95% CI 0.43-1.38] or at Week 52 [45.1% vs 40.6%; aOR 1.14, 0.70-1.86], and in CD clinical remission [CD activity index score ≤150] rates at Week 6 [41.4% vs 35.1%; 1.26, 0.86-1.85] or at Week 52 [49.6% vs 37.8%; 1.35, 0.91-1.99]. The incidence of enteric and all infections in vedolizumab IV/SC-treated patients was low with and without 5-ASA. CONCLUSION Continuation of concomitant oral 5-ASA after starting vedolizumab had no significant impact on clinical and endoscopic outcomes. CLINICAL TRIAL IDENTIFIERS GEMINI 1: NCT00783718, EudraCT 2008-002782-32; GEMINI 2: NCT00783692, EudraCT 2008-00278-33; GEMINI 3: NCT01224171, EudraCT 2009-016488-12; GEMINI long-term safety study: NCT00790933, EudraCT 2008-002784-14; VISIBLE 1: NCT02611830, EudraCT 2015-000480-14; VISIBLE 2: NCT02611817, EudraCT 2015-000481-58; VISIBLE open-label extension: NCT02620046, EudraCT 2015-000482-31.
Collapse
Affiliation(s)
- Ryan C Ungaro
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Harisha Kadali
- Takeda, Global Patient Safety and Evaluation, Cambridge, MA, USA
| | - Wenwen Zhang
- Takeda, Statistical and Quantitative Sciences, Cambridge, MA, USA
| | - Shashi Adsul
- Takeda, Global Medical Affairs, Cambridge, MA, USA
| | - Walter Reinisch
- Medical University of Vienna, Department of Internal Medicine III, Vienna, Austria
| |
Collapse
|
|
6
|
Yang X, Zeng D, Li C, Yu W, Xie G, Zhang Y, Lu W. Therapeutic potential and mechanism of functional oligosaccharides in inflammatory bowel disease: a review. FOOD SCIENCE AND HUMAN WELLNESS 2023. [DOI: 10.1016/j.fshw.2023.03.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/08/2023]
|
|
7
|
Wang T, Wang P, Yin L, Wang X, Shan Y, Yi Y, Zhou Y, Liu B, Wang X, Lü X. Dietary Lactiplantibacillus plantarum KX041 attenuates colitis-associated tumorigenesis and modulates gut microbiota. FOOD SCIENCE AND HUMAN WELLNESS 2023. [DOI: 10.1016/j.fshw.2023.02.012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 03/29/2023]
|
|
8
|
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.
Collapse
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
| |
Collapse
|
|
9
|
Wu H, Wu Z, Qiu Y, Zhao F, Liao M, Zhong Z, Chen J, Zeng Y, Liu R. Supplementing a specific synbiotic suppressed the incidence of AOM/DSS-induced colorectal cancer in mice. iScience 2023; 26:106979. [PMID: 37378327 PMCID: PMC10291512 DOI: 10.1016/j.isci.2023.106979] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2022] [Revised: 04/11/2023] [Accepted: 05/24/2023] [Indexed: 06/29/2023] Open
Abstract
In this study, we evaluated the effect of a specific synbiotic on CAC (AOM/DSS-induced colitis-associated cancer). We confirmed that the synbiotic intervention was able to protect the intestinal barrier and inhibit CAC occurrence via upregulating tight junction proteins and anti-inflammatory cytokines, and downregulating pro-inflammatory cytokines. Moreover, the synbiotic significantly improved the disorder of the colonic microbiota of CAC mice, promoted the formation of SCFAs and the production of secondary bile acids, and alleviated the accumulation of primary bile acids in the CAC mice. Meanwhile, the synbiotic could significantly inhibit the abnormal activation of the intestinal Wnt/β-catenin signaling pathway significantly related to IL-23. In a word, the synbiotic can inhibit the occurrence and development of colorectal tumors and it may be a functional food to prevent inflammation-related colon tumors, and the research also provided a theoretical basis for improving the intestinal microecological environment through diet therapy.
Collapse
Affiliation(s)
- Huixia Wu
- Department of Medical Laboratory, School of Medicine, Hunan Normal University, Changsha 410013, China
| | - Zhengchun Wu
- Department of Hepatobiliary and Intestinal Surgery, Hunan Cancer Hospital and the Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China
| | - Yilan Qiu
- School of Life Science, Hunan Normal University, Changsha 410018, China
- Changsha Tianan Biotechnology Co., Ltd., Changsha 410018, China
| | - Fangjian Zhao
- Medical Laboratory, The First Affiliated Hospital of Hunan Normal University, Changsha 410018, China
| | - Minjing Liao
- Department of Medical Laboratory, School of Medicine, Hunan Normal University, Changsha 410013, China
| | - Zhihong Zhong
- Department of Medical Laboratory, School of Medicine, Hunan Normal University, Changsha 410013, China
| | - Jian Chen
- Medical Laboratory, The First Affiliated Hospital of Hunan Normal University, Changsha 410018, China
| | - Yiliang Zeng
- Shaoshan Changbaitong Biological Technology Co., Ltd., Shaoshan 411100, China
| | - Rushi Liu
- Department of Medical Laboratory, School of Medicine, Hunan Normal University, Changsha 410013, China
| |
Collapse
|
|
10
|
Horio Y, Uchino M, Igeta M, Nagano K, Kusunoki K, Kuwahara R, Kimura K, Kataoka K, Beppu N, Ikeda M, Ikeuchi H. Risk factors for the postoperative recurrence of ulcerative colitis-associated colorectal cancer. Int J Colorectal Dis 2023; 38:113. [PMID: 37138034 DOI: 10.1007/s00384-023-04410-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 04/16/2023] [Indexed: 05/05/2023]
Abstract
PURPOSE Although ulcerative colitis-associated colorectal cancer (UC-CRC) has been described, there are few reports regarding recurrent cases of UC-CRC. In this study, we investigated the risk factors for UC-CRC recurrence. METHODS Recurrence-free survival (RFS) was determined for 144 stage I to III cancer patients among 210 UC-CRC patients from August 2002 to August 2019. The Kaplan‒Meier method was used to obtain the cumulative RFS rate, and the Cox proportional hazard model was used to extract recurrence risk factors. The interaction term between cancer stage and prognostic factors specific to UC-CRC was evaluated using the Cox model. The Kaplan‒Meier method was applied by cancer stage to the UC-CRC-specific prognostic factors for which interaction effects were indicated. RESULTS There were 18 cases of recurrence involving patients with stage I to III cancer, and the recurrence rate was 12.5%. The cumulative 5-year RFS rate was 87.5%. Multivariable analysis showed that age at surgery (hazard ratio (HR): 0.95, 95% CI: 0.91-0.99, p = 0.02), undifferentiated carcinoma (HR: 4.42, 95% CI: 1.13-17.24, p = 0.03), lymph node metastasis (HR: 4.11, 95% CI: 1.08-15.69, p = 0.03), and vascular invasion (HR: 8.01, 95% CI: 1.54-41.65, p = 0.01) were significant risk factors for recurrence. Patients with stage III CRC in the young adult (age < 50 years) group had a significantly worse prognosis than those in the adult (age ≥ 50 years) group (p < 0.01). CONCLUSION Age at surgery was identified as a risk factor for UC-CRC recurrence. Young adult patients with stage III cancer may have a poor prognosis.
Collapse
Affiliation(s)
- Yuki Horio
- Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan.
- Department of Gastrointestinal Surgery, Hyogo Medical University, 1-1, Mukogawa-Cho, Hyogo, 663-8501, Nishinomiya, Japan.
| | - Motoi Uchino
- Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan
| | - Masataka Igeta
- Department of Biostatistics, Hyogo Medical University, Hyogo, Japan
| | - Kentaro Nagano
- Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan
| | - Kurando Kusunoki
- Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan
| | - Ryuichi Kuwahara
- Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan
| | - Kei Kimura
- Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan
| | - Kozo Kataoka
- Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan
| | - Naohito Beppu
- Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan
| | - Masataka Ikeda
- Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan
| | - Hiroki Ikeuchi
- Department of Gastroenterological Surgery, Hyogo Medical University, Hyogo, Japan
| |
Collapse
|
|
11
|
Viola A, Demarzo MG, Abbruzzese A, Muscianisi M, Chiappetta MF, Costantino G, Ksissa O, Alibrandi A, Fries W. Low Adherence is Associated with Chronic Active Disease in Ulcerative Colitis: A Retrospective Study from a Single Referral Center. Patient Prefer Adherence 2023; 17:807-816. [PMID: 36992866 PMCID: PMC10041981 DOI: 10.2147/ppa.s390349] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/26/2022] [Accepted: 02/18/2023] [Indexed: 03/31/2023] Open
Abstract
PURPOSE New therapeutic approaches for ulcerative colitis (UC) are now available, but there is still no robust evidence for predictors of poor outcomes. We aimed to evaluate the factors associated with a chronic active UC disease course. PATIENTS AND METHODS Data of all UC outpatients followed for at least 3 years after diagnosis between 2005 and 2018 were retrospectively collected. The primary aim was to identify risk factors for chronic active disease 3 years after diagnosis. Moreover, the following variables were investigated: proximal disease extension or disease regression, proctocolectomy, early use of biologics (BIO) or immunomodulators (IMM), hospitalization, colorectal cancer, and adherence. We defined adherence as both, taking the prescribed therapy and constancy in scheduled follow-up visits. RESULTS A total of 345 UC patients followed for a median period of 82 months were included. Patients with extensive colitis at diagnosis had a higher rate of chronic active disease 3 years after diagnosis (p<0.012) together with a higher rate of surgery (p<0.001) at maximum follow-up. Patients with pancolitis showed significant disease regression over time (51%) without differences in treatment. The only factor associated with chronic active disease was non-adherence (p < 0.03; OR 0.49, 95% CI: 0.26-0.95). Adherent patients developed chronic active disease (p<0.025) less frequently but did receive more frequent IMM (p<0.045) or BIO (p<0.009) therapy. CONCLUSION Patients diagnosed with pancolitis were more likely to have chronic active disease and to undergo colectomy. The only predictor for developing chronically active UC regardless of disease extension was the lack of adherence to therapy within the first 3 years after diagnosis, underlining the importance of tight control of UC patients and the need to timely identify potential risk factors for non-adherence.
Collapse
Affiliation(s)
- Anna Viola
- Department of Clinical and Experimental Medicine, IBD-Unit, University of Messina, Messina, Italy
| | - Maria Giulia Demarzo
- Department of Clinical and Experimental Medicine, IBD-Unit, University of Messina, Messina, Italy
- Department of Internal Medicine, Ospedale Policlinico San Martino-IRCCS per l’Oncologia, Gastroenterology Unit, University of Genoa, Genoa, Italy
| | - Alfredo Abbruzzese
- Department of Clinical and Experimental Medicine, IBD-Unit, University of Messina, Messina, Italy
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
| | - Marco Muscianisi
- Department of Clinical and Experimental Medicine, IBD-Unit, University of Messina, Messina, Italy
| | - Michele Francesco Chiappetta
- Department of Clinical and Experimental Medicine, IBD-Unit, University of Messina, Messina, Italy
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
| | - Giuseppe Costantino
- Department of Clinical and Experimental Medicine, IBD-Unit, University of Messina, Messina, Italy
| | - Omar Ksissa
- Department of Clinical and Experimental Medicine, IBD-Unit, University of Messina, Messina, Italy
- Department of Health Promotion, Mother & Child Care, Internal Medicine & Medical Specialties, PROMISE, Gastroenterology & Hepatology Unit, University of Palermo, Palermo, Italy
| | - Angela Alibrandi
- Department of Economics; Unit of Statistical and Mathematical Sciences, University of Messina, Messina, Italy
| | - Walter Fries
- Department of Clinical and Experimental Medicine, IBD-Unit, University of Messina, Messina, Italy
| |
Collapse
|
|
12
|
Patton EA, Cunningham P, Noneman M, Helms HP, Martinez-Muniz G, Sumal AS, Dhameja MK, Unger CA, Alahdami AK, Enos RT, Chatzistamou I, Velázquez KT. Acute Administration of Ojeok-san Ameliorates Pain-like Behaviors in Pre-Clinical Models of Inflammatory Bowel Diseases. Nutrients 2023; 15:nu15071559. [PMID: 37049400 PMCID: PMC10096710 DOI: 10.3390/nu15071559] [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: 02/07/2023] [Revised: 03/20/2023] [Accepted: 03/21/2023] [Indexed: 04/14/2023] Open
Abstract
(1) Background: Gastrointestinal pain and fatigue are the most reported concerns of patients with inflammatory bowel disease (IBD). Commonly prescribed drugs focus on decreasing excessive inflammation. However, up to 20% of IBD patients in an "inactive" state experience abdominal pain. The medicinal herb Ojeok-san (OJS) has shown promise in the amelioration of visceral pain. However, no research on OJS has been conducted in preclinical models of IBD. The mechanism by which OJS promotes analgesia is still elusive, and it is unclear if OJS possesses addictive properties. (2) Aims: In this study, we examined the potential of OJS to promote analgesic effects and rewarding behavior. Additionally, we investigated if tumor necrosis factor alpha (TNFα) from macrophages is a primary culprit of IBD-induced nociception. (3) Methods: Multiple animal models of IBD were used to determine if OJS can reduce visceral nociception. TNFα-macrophage deficient mice were used to investigate the mechanism of action by which OJS reduces nociceptive behavior. Mechanical sensitivity and operant conditioning tests were used to determine the analgesic and rewarding effects of OJS. Body weight, colon length/weight, blood in stool, colonic inflammation, and complete blood count were assessed to determine disease progression. (4) Results: OJS reduced the evoked mechanical nociception in the dextran sulphate sodium model of colitis and IL-10 knockout (KO) mice and delayed aversion to colorectal distension in C57BL/6 mice. No rewarding behavior was observed in OJS-treated IL-10 KO and mdr1a KO mice. The analgesic effects of OJS are independent of macrophage TNFα levels and IBD progression. (5) Conclusions: OJS ameliorated elicited mechanical and visceral nociception without producing rewarding effects. The analgesic effects of OJS are not mediated by macrophage TNFα.
Collapse
Affiliation(s)
- Emma A Patton
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA
| | - Patrice Cunningham
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA
| | - Matthew Noneman
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA
| | - Henry P Helms
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA
| | - Gustavo Martinez-Muniz
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA
| | - Aman S Sumal
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA
| | - Milan K Dhameja
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA
| | - Christian A Unger
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA
| | - Ahmed K Alahdami
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA
| | - Reilly T Enos
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA
| | - Ioulia Chatzistamou
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA
| | - Kandy T Velázquez
- Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC 29209, USA
| |
Collapse
|
|
13
|
Wei X, Leng X, Li G, Wang R, Chi L, Sun D. Advances in research on the effectiveness and mechanism of Traditional Chinese Medicine formulas for colitis-associated colorectal cancer. Front Pharmacol 2023; 14:1120672. [PMID: 36909166 PMCID: PMC9995472 DOI: 10.3389/fphar.2023.1120672] [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: 12/10/2022] [Accepted: 02/13/2023] [Indexed: 02/25/2023] Open
Abstract
Inflammatory bowel disease (IBD) can progress into colitis-associated colorectal cancer (CAC) through the inflammation-cancer sequence. Although the mechanism of carcinogenesis in IBD has not been fully elucidated, the existing research indicates that CAC may represent a fundamentally different pathogenesis pattern of colorectal cancer. At present, there is no proven safe and effective medication to prevent IBD cancer. In recent years, Chinese medicine extracts and Chinese medicine monomers have been the subject of numerous articles about the prevention and treatment of CAC, but their clinical application is still relatively limited. Traditional Chinese Medicine (TCM) formulas are widely applied in clinical practice. TCM formulas have demonstrated great potential in the prevention and treatment of CAC in recent years, although there is still a lack of review. Our work aimed to summarize the effects and potential mechanisms of TCM formulas for the prevention and treatment of CAC, point out the issues and limitations of the current research, and provide recommendations for the advancement of CAC research in the future. We discovered that TCM formulas regulated many malignant biological processes, such as inflammation-mediated oxidative stress, apoptosis, tumor microenvironment, and intestinal microecology imbalance in CAC, through a review of the articles published in databases such as PubMed, SCOPUS, Web of Science, Embase, and CNKI. Several major signal transduction pathways, including NF-κB, STAT3, Wnt/β-catenin, HIF-1α, and Nrf2, were engaged. TCM formula may be a promising treatment candidate to control the colitis-cancer transformation, however further high-quality research is required.
Collapse
Affiliation(s)
- Xiunan Wei
- College of First Clinical Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Xiaohui Leng
- Weifang Traditional Chinese Hospital, Weifang, China
| | - Gongyi Li
- College of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Ruting Wang
- College of Chinese Medicine, Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Lili Chi
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| | - Dajuan Sun
- Affiliated Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China
| |
Collapse
|
|
14
|
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: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [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.
Collapse
|
|
15
|
Effects of Cheonggukjang (Fermented Soybean) on the Development of Colitis-Associated Colorectal Cancer in Mice. Foods 2023; 12:foods12020383. [PMID: 36673473 PMCID: PMC9858590 DOI: 10.3390/foods12020383] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2022] [Revised: 01/09/2023] [Accepted: 01/11/2023] [Indexed: 01/15/2023] Open
Abstract
Colorectal cancer (CRC) is the third most common type of cancer and is caused by multiple factors. Chronic inflammation, known to cause inflammatory bowel disease (IBD), is closely associated with CRC. Cheonggukjang (CJ), a traditional Korean fermented soybean, is a functional food with anti-inflammatory effects in the intestines, but its anti-cancer effects have not yet been explored. In this study, we investigated the cancer-protective effects of cheonggukjang in an azoxymethane/DSS (AOM/DSS)-induced colitis-associated colorectal cancer (CAC) mouse model. The CJ alleviated AOM/DSS-induced pathological symptoms such as colonic shortening, increased spleen weight, tumor formation, and histological changes. It also modulated pro-inflammatory and anti-inflammatory cytokine levels via the suppression of NF-κB and inflammatory mediator signaling pathways. Furthermore, the CJ improved intestinal integrity by regulating mucin-associated and tight junction proteins. In addition, it suppressed tumor growth by regulating apoptosis and proliferation. These results highlight the anti-tumor effects of CJ in an AOM/DSS-induced CAC mouse model.
Collapse
|
|
16
|
Copper-olsalazine metal-organic frameworks as a nanocatalyst and epigenetic modulator for efficient inhibition of colorectal cancer growth and metastasis. Acta Biomater 2022; 152:495-506. [PMID: 36087871 DOI: 10.1016/j.actbio.2022.08.076] [Citation(s) in RCA: 23] [Impact Index Per Article: 7.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/05/2022] [Revised: 08/16/2022] [Accepted: 08/31/2022] [Indexed: 11/23/2022]
Abstract
Despite the extensive explorations of nanoscale metal-organic frameworks (nanoMOFs) in drug delivery, the intrinsic bioactivity of nanoMOFs, such as anticancer activity, is severely underestimated owing to the overlooked integration of the hierarchical components including nanosized MOFs and molecular-level organic ligands and metal-organic complexes. Herein, we propose a de novo design of multifunctional bioactive nanoMOFs ranging from molecular to nanoscale level, and demonstrate this proof-of-concept by a copper-olsalazine (Olsa, a clinically approved drug for inflammatory bowel disease, here as a bioactive linker and DNA hypomethylating agent) nanoMOF displaying a multifaceted anticancer mechanism: (1) Cu-Olsa nanoMOF-mediated redox dyshomeostasis for enhanced catalytic tumor therapy, (2) targeting downregulation of cyclooxygenase-2 by the organic complex of Cu2+ and Olsa, and (3) Olsa-mediated epigenetic regulation. Cu-Olsa nanoMOF displayed an enzyme-like catalytic activity to generate cancericidal species ·OH and 1O2 from rich H2O2 in tumors, improved the expression of tumor suppressors TIMP3 and AXIN2 by epigenetic modulation, and fulfilled selective inhibition of colorectal cancer cells over normal cells. The hyaluronic acid-modified nanoMOF further verified the efficient suppression of CT26 colorectal tumor growth and metastasis in murine models. Overall, these results suggest that Olsa-based MOF presents a platform of epigenetic therapy-synergized nanomedicine for efficient cancer treatment and provides a powerful strategy for the design of intrinsically bioactive nanoMOFs. STATEMENT OF SIGNIFICANCE: Metal-organic frameworks (MOFs) with intrinsic bioactivities such as anticancer and antibacterial activity are of great interest. Herein, we reported a bioactive copper-olsalazine (Cu-Olsa) nanoMOF as a nanodrug for colorectal cancer treatment. This nanoMOF per se displayed enzyme-like catalytic activity to generate cancericidal species ·OH and 1O2 from rich H2O2 in tumors for nanocatalytic tumor therapy. Upon dissociation into small molecular copper-organic complex and olsalazine in cancer cells, COX-2 inhibition and epigenetic modulation were fulfilled for selective inhibition of colorectal cancer growth and metastasis.
Collapse
|
|
17
|
Colorectal Cancer in Ulcerative Colitis: Mechanisms, Surveillance and Chemoprevention. Curr Oncol 2022; 29:6091-6114. [PMID: 36135048 PMCID: PMC9498229 DOI: 10.3390/curroncol29090479] [Citation(s) in RCA: 44] [Impact Index Per Article: 14.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/11/2022] [Revised: 08/14/2022] [Accepted: 08/18/2022] [Indexed: 11/17/2022] Open
Abstract
Patients with ulcerative colitis (UC) are at a two- to three-fold increased risk of developing colorectal cancer (CRC) than the general population based on population-based data. UC-CRC has generated a series of clinical problems, which are reflected in its worse prognosis and higher mortality than sporadic CRC. Chronic inflammation is a significant contributor to the development of UC-CRC, so comprehending the relationship between the proinflammatory factors and epithelial cells together with downstream signaling pathways is the core to elucidate the mechanisms involved in developing of CRC. Clinical studies have shown the importance of early prevention, detection and management of CRC in patients with UC, and colonoscopic surveillance at regular intervals with multiple biopsies is considered the most effective way. The use of endoscopy with targeted biopsies of visible lesions has been supported in most populations. In contrast, random biopsies in patients with high-risk characteristics have been suggested during surveillance. Some of the agents used to treat UC are chemopreventive, the effects of which will be examined in cancers in UC in a population-based setting. In this review, we outline the current state of potential risk factors and chemopreventive recommendations in UC-CRC, with a specific focus on the proinflammatory mechanisms in promoting CRC and evidence for personalized surveillance.
Collapse
|
|
18
|
Akiyama S, Fukuda S, Steinberg JM, Suzuki H, Tsuchiya K. Characteristics of inflammatory bowel diseases in patients with concurrent immune-mediated inflammatory diseases. World J Gastroenterol 2022; 28:2843-2853. [PMID: 35978883 PMCID: PMC9280738 DOI: 10.3748/wjg.v28.i25.2843] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Revised: 03/10/2022] [Accepted: 05/28/2022] [Indexed: 02/06/2023] Open
Abstract
Patients with inflammatory bowel disease (IBD) are more likely to have concurrent immune-mediated inflammatory diseases (IMIDs) than those without IBD. IMIDs have been observed to alter the phenotype and outcomes of IBD in recent studies. Several studies have found that IBD patients with concurrent IMIDs may have more extensive or severe disease phenotypes, and are considered to be at increased risk of requiring biologics and IBD-related surgeries, suggesting that having multiple IMIDs is a poor prognostic factor for IBD. Furthermore, IBD patients with primary sclerosing cholangitis and Takayasu arteritis are reported to have unique endoscopic phenotypes, suggesting concurrent IMIDs can influence IBD phenotype with specific intestinal inflammatory distributions. In this review, we discuss the pathogenesis, disease phenotypes, and clinical outcomes in IBD patients with concomitant IMIDs.
Collapse
Affiliation(s)
- Shintaro Akiyama
- Department of Gastroenterology, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
| | - Soma Fukuda
- Department of Gastroenterology, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
| | - Joshua M Steinberg
- Inflammatory Bowel Disease, Gastroenterology of the Rockies, Denver, CO 80218, United States
| | - Hideo Suzuki
- Department of Gastroenterology, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
| | - Kiichiro Tsuchiya
- Department of Gastroenterology, University of Tsukuba, Tsukuba 305-8575, Ibaraki, Japan
| |
Collapse
|
|
19
|
Rivera AP, Flores Monar GV, Islam H, Puttagunta SM, Islam R, Kundu S, Jha SB, Sange I. Ulcerative Colitis-Induced Colorectal Carcinoma: A Deleterious Concatenation. Cureus 2022; 14:e22636. [PMID: 35371788 PMCID: PMC8959421 DOI: 10.7759/cureus.22636] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 02/26/2022] [Indexed: 12/13/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal ailment that encompasses Crohn's disease (CD) and ulcerative colitis (UC). UC is an idiopathic, chronic inflammatory condition of the colonic mucosa that begins in the rectum and progresses proximally in a continuous way over a portion of the entire colon. Chronic inflammation is linked to cancer, and IBD-related chronic colonic inflammation raises the risk of colorectal cancer. Chronic inflammation has been linked to cancer, and chronic colonic inflammation caused by IBD increases the risk of colorectal cancer (CRC). When CRC arises in people with IBD, unlike sporadic CRC, the lesions are difficult to identify due to mucosal alterations produced by inflammation. The total prevalence of IBD-associated CRC is increasing due to the rapidly increasing frequency of IBD. Screening and surveillance colonoscopy in IBD patients is considered to allow for the early diagnosis of dysplasia and cancer, improving the prognosis of IBD-related CRC by giving patients proactive therapy. This article has reviewed literature pertaining to the mechanisms related to CRC development in UC and its clinical and therapeutic implications.
Collapse
Affiliation(s)
- Ana P Rivera
- Research, Universidad Americana (UAM) Facultad de Medicina, Managua, NIC
| | | | - Hamza Islam
- Research, Faisalabad Medical University, Faisalabad, PAK
| | | | - Rabia Islam
- Research, Faisalabad Medical University, Faisalabad, PAK
| | | | | | - Ibrahim Sange
- Research, K. J. Somaiya Medical College, Hospital and Research Center, Mumbai, IND
| |
Collapse
|
|
20
|
Suzuki K, Fujii H, Yamauchi T, Kato‐Hayashi H, Ishihara M, Iihara H, Hirose C, Nishida S, Funato M, Kobayashi R, Yasuda K, Ino Y, Tamaki H, Yamashita S, Iguchi K, Noguchi Y, Teramachi H, Takada J, Kubota M, Ibuka T, Araki H, Shimizu M, Suzuki A. Questionnaire survey to identify meal habits which influence adherence to oral 5‐aminosalicylic acid regimens in patients with ulcerative colitis. JOURNAL OF PHARMACY PRACTICE AND RESEARCH 2021. [DOI: 10.1002/jppr.1712] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Affiliation(s)
- Keiko Suzuki
- Department of Pharmacy Gifu University Hospital Gifu Japan
| | - Hironori Fujii
- Department of Pharmacy Gifu University Hospital Gifu Japan
| | | | | | | | | | - Chiemi Hirose
- Department of Pharmacy Gifu University Hospital Gifu Japan
| | - Shohei Nishida
- Department of Pharmacy Gifu University Hospital Gifu Japan
| | - Miyui Funato
- Department of Pharmacy Gifu University Hospital Gifu Japan
| | - Ryo Kobayashi
- Department of Pharmacy Gifu University Hospital Gifu Japan
| | - Koji Yasuda
- Department of Pharmacy Gifu University Hospital Gifu Japan
| | - Yoko Ino
- Gifu Pharmaceutical University Pharmacy Gifu Japan
| | | | | | | | | | | | - Jun Takada
- Department of Gastroenterology Gifu University Graduate School of Medicine Gifu Japan
| | - Masaya Kubota
- Department of Gastroenterology Gifu University Graduate School of Medicine Gifu Japan
| | - Takashi Ibuka
- Department of Gastroenterology Gifu University Graduate School of Medicine Gifu Japan
| | - Hiroshi Araki
- Department of Gastroenterology Gifu University Graduate School of Medicine Gifu Japan
| | - Masahito Shimizu
- Department of Gastroenterology Gifu University Graduate School of Medicine Gifu Japan
| | - Akio Suzuki
- Department of Pharmacy Gifu University Hospital Gifu Japan
| |
Collapse
|
|
21
|
Tripathi K, Dong J, Mishkin BF, Feuerstein JD. Patient Preference and Adherence to Aminosalicylates for the Treatment of Ulcerative Colitis. Clin Exp Gastroenterol 2021; 14:343-351. [PMID: 34511961 PMCID: PMC8412827 DOI: 10.2147/ceg.s237653] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2021] [Accepted: 08/14/2021] [Indexed: 12/11/2022] Open
Abstract
Ulcerative colitis (UC) is a chronic inflammatory disorder that requires sustained treatment for optimal outcomes. The 5-aminosalicylate (5-ASA) class of medications are first-line for the treatment of mild-to-moderate UC but suffer from suboptimal adherence rates in real-world settings. This review summarizes the literature on adherence and patient preference to 5-ASA in patients with UC. We begin by highlighting key studies that measure real-world adherence rates, as well as some of the pitfalls associated with certain techniques. We examine the data on the consequences of non-adherence, which range from decreased quality of life and higher risk of colorectal cancer at the individual level to increased costs to the overall healthcare system. We then turn to the reasons and risk factors for non-adherence and summarize the current understanding of the barriers towards adherence. Afterwards, we describe the research on patient preferences between 5-ASA formulations and dosing regimen. Finally, we summarize the evidence regarding interventions to improve 5-ASA adherence. While adherence remains a challenge in practice, understanding the current state of the field can better inform future efforts towards increasing adherence, and thus clinical outcomes, in UC.
Collapse
Affiliation(s)
- Kartikeya Tripathi
- Department of Gastroenterology, University of Massachusetts Medical School - Baystate Campus, Springfield, MA, USA
| | - Jeffrey Dong
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Brooke F Mishkin
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| | - Joseph D Feuerstein
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA
| |
Collapse
|
|
22
|
Blackwell J, Saxena S, Petersen I, Hotopf M, Creese H, Bottle A, Alexakis C, Pollok RC. Depression in individuals who subsequently develop inflammatory bowel disease: a population-based nested case-control study. Gut 2021; 70:1642-1648. [PMID: 33109601 DOI: 10.1136/gutjnl-2020-322308] [Citation(s) in RCA: 41] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/23/2020] [Revised: 10/01/2020] [Accepted: 10/04/2020] [Indexed: 12/20/2022]
Abstract
OBJECTIVE Depression is a potential risk factor for developing IBD. This association may be related to GI symptoms occurring before diagnosis. We aimed to determine whether depression, adjusted for pre-existing GI symptoms, is associated with subsequent IBD. DESIGN We conducted a nested case-control study using the Clinical Practice Research Datalink identifying incident cases of UC and Crohn's disease (CD) from 1998 to 2016. Controls without IBD were matched for age and sex. We measured exposure to prevalent depression 4.5-5.5 years before IBD diagnosis. We created two sub-groups with prevalent depression based on whether individuals had reported GI symptoms before the onset of depression. We used conditional logistic regression to derive ORs for the risk of IBD depending on depression status. RESULTS We identified 10 829 UC cases, 4531 CD cases and 15 360 controls. There was an excess of prevalent depression 5 years before IBD diagnosis relative to controls (UC: 3.7% vs 2.7%, CD 3.7% vs 2.9%). Individuals with GI symptoms prior to the diagnosis of depression had increased adjusted risks of developing UC and CD compared with those without depression (UC: OR 1.47, 95% CI 1.21 to 1.79; CD: OR 1.41, 95% CI 1.04 to 1.92). Individuals with depression alone had similar risks of UC and CD to those without depression (UC: OR 1.13, 95% CI 0.99 to 1.29; CD: OR 1.12, 95% CI 0.91 to 1.38). CONCLUSIONS Depression, in the absence of prior GI symptoms, is not associated with subsequent development of IBD. However, depression with GI symptoms should prompt investigation for IBD.
Collapse
Affiliation(s)
| | - Sonia Saxena
- School of Primary Care and Public Health, Imperial College, London, UK
| | - Irene Petersen
- Department of Primary Care and Population Health, University College London, London, UK.,Department of Clinical Epidemiology, Aarhus University, Aarhus, Denmark
| | - Matthew Hotopf
- Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.,South London and Maudsley NHS Foundation Trust, London, UK
| | - Hanna Creese
- School of Primary Care and Public Health, Imperial College, London, UK
| | - Alex Bottle
- School of Primary Care and Public Health, Imperial College, London, UK.,Dr Foster Unit, School of Primary Care and Public Health, Imperial College, London, UK
| | - Christopher Alexakis
- Gastroenterology, Royal Surrey County Hospital NHS Foundation Trust, Guildford, Surrey, UK
| | - Richard C Pollok
- Gastroenterology, St George's University of London, London, UK .,Institute of Infection and Immunity, University of London St George's, London, UK
| | | |
Collapse
|
|
23
|
Wang T, Zhang L, Wang P, Liu Y, Wang G, Shan Y, Yi Y, Zhou Y, Liu B, Wang X, Lü X. Lactobacillus coryniformis MXJ32 administration ameliorates azoxymethane/dextran sulfate sodium-induced colitis-associated colorectal cancer via reshaping intestinal microenvironment and alleviating inflammatory response. Eur J Nutr 2021; 61:85-99. [PMID: 34185157 DOI: 10.1007/s00394-021-02627-8] [Citation(s) in RCA: 29] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2021] [Accepted: 06/24/2021] [Indexed: 12/24/2022]
Abstract
PURPOSE Gut microbiota has been reported to contribute to either prevent or promote colorectal cancer (CRC), and treatment with probiotics might be a promising intervention method. The present study aimed to evaluate the potential anti-CRC effects of Lactobacillus coryniformis MXJ32 on a colitis-associated (CA)-CRC mouse model. METHODS The CA-CRC mouse model was induced by a single intraperitoneal injection of 10 mg/kg azoxymethane and followed by three 7-day cycles of 2% dextran sulfate sodium in drinking water with a 14-day recovery period. Mice were supplemented with L. coryniformis MXJ32 by oral gavage (1 × 109 CFU/day/mouse). The CA-CRC attenuating effects of this probiotic were assessed via intestinal barrier integrity, inflammation, and gut microenvironment. RESULTS Treatment with L. coryniformis MXJ32 could significantly inhibit the total number of tumors and the average tumor diameter. This probiotic administration prevented the damage of intestinal barrier function by enhancing the expression of tight junction proteins (Occludin, Claudin-1, and ZO-1) and recovering the loss of goblet cells. Moreover, L. coryniformis MXJ32 alleviated intestinal inflammation via down-regulating the expression of inflammatory cytokines (TNF-α, IL-1β, IL-6, IL-γ, and IL-17a) and chemokines (Cxcl1, Cxcl2, Cxcl3, Cxcl5, and Ccl7). In addition, L. coryniformis MXJ32 supplementation increased the abundance of some beneficial bacteria (such as SCFAs-producing bacteria, Lactobacillus, Bifidobacterium, Akkermansia, and Faecalibaculum) and decreased the abundance of some harmful bacteria (such as pro-inflammatory bacteria, Desulfovibrio and Helicobacter), which in turn attenuated the overexpression of inflammation. CONCLUSION Lactobacillus coryniformis MXJ32 could effectively ameliorate CA-CRC via regulating intestinal microenvironment, alleviating inflammation, and intestinal barrier damage, which further suggested that L. coryniformis MXJ32 could be considered as a functional food ingredient for the alleviation of CA-CRC.
Collapse
Affiliation(s)
- Tao Wang
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Leshan Zhang
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Panpan Wang
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Yilin Liu
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Gangtu Wang
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Yuanyuan Shan
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Yanglei Yi
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Yuan Zhou
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China
| | - Bianfang Liu
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China.
| | - Xin Wang
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China.
| | - Xin Lü
- College of Food Science and Engineering, Northwest Agriculture and Forestry University, No. 22 Xinong Road, Yangling District, Xianyang, 712100, Shaanxi, China.
| |
Collapse
|
|
24
|
Yalchin M, Baker AM, Graham TA, Hart A. Predicting Colorectal Cancer Occurrence in IBD. Cancers (Basel) 2021; 13:2908. [PMID: 34200768 PMCID: PMC8230430 DOI: 10.3390/cancers13122908] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/12/2021] [Revised: 05/27/2021] [Accepted: 06/01/2021] [Indexed: 12/13/2022] Open
Abstract
Patients with colonic inflammatory bowel disease (IBD) are at an increased risk of developing colorectal cancer (CRC), and are therefore enrolled into a surveillance programme aimed at detecting dysplasia or early cancer. Current surveillance programmes are guided by clinical, endoscopic or histological predictors of colitis-associated CRC (CA-CRC). We have seen great progress in our understanding of these predictors of disease progression, and advances in endoscopic technique and management, along with improved medical care, has been mirrored by the falling incidence of CA-CRC over the last 50 years. However, more could be done to improve our molecular understanding of CA-CRC progression and enable better risk stratification for patients with IBD. This review summarises the known risk factors associated with CA-CRC and explores the molecular landscape that has the potential to complement and optimise the existing IBD surveillance programme.
Collapse
Affiliation(s)
- Mehmet Yalchin
- Inflammatory Bowel Disease Department, St. Mark’s Hospital, Watford R.d., Harrow HA1 3UJ, UK
- Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse S.q., London EC1M 6BQ, UK; (A.-M.B.); (T.A.G.)
| | - Ann-Marie Baker
- Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse S.q., London EC1M 6BQ, UK; (A.-M.B.); (T.A.G.)
| | - Trevor A. Graham
- Centre for Genomics and Computational Biology, Barts Cancer Institute, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse S.q., London EC1M 6BQ, UK; (A.-M.B.); (T.A.G.)
| | - Ailsa Hart
- Inflammatory Bowel Disease Department, St. Mark’s Hospital, Watford R.d., Harrow HA1 3UJ, UK
| |
Collapse
|
|
25
|
He R, Han C, Li Y, Qian W, Hou X. Cancer-Preventive Role of Bone Marrow-Derived Mesenchymal Stem Cells on Colitis-Associated Colorectal Cancer: Roles of Gut Microbiota Involved. Front Cell Dev Biol 2021; 9:642948. [PMID: 34150751 PMCID: PMC8212064 DOI: 10.3389/fcell.2021.642948] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2020] [Accepted: 02/26/2021] [Indexed: 01/07/2023] Open
Abstract
BACKGROUND Mesenchymal stem cells (MSCs) treatment showed promising results in inflammatory bowel disease in both rodent models and patients. Nevertheless, previous studies conducted conflicting results on preclinical tumor models treated with MSCs concerning their influence on tumor initiation and progression. This study is designed to demonstrate the role of bone marrow-derived MSCs and the potential mechanism in the colitis-associated colon cancer (CAC) model. METHODS Bone marrow-derived MSCs were isolated from green fluorescent protein-transgenic mice, cultured, and identified by flow cytometry. Azoxymethane and dextran sulfate sodium were administrated to establish the CAC mouse model, and MSCs were infused intraperitoneally once per week. The mice were weighed weekly, and colon length, tumor number, and average tumor size were assessed after the mice were killed. MSC localization was detected by immunofluorescence staining; tumor cell proliferation and apoptosis were measured by immunohistochemistry staining of Ki-67 and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end labeling assay, respectively. The colonic tumor tissues were isolated for RNA-seq, and fecal samples were collected for 16S ribosomal RNA sequencing of the microbiome. RESULTS After injection intraperitoneally, MSCs migrated to the intestine and inhibited the initiation of colitis-associated colorectal cancer. This inhibition effect was marked by less weight loss, longer colon length, and reduced tumor numbers. Moreover, MSCs reduced tumor cell proliferation and induced tumor cell apoptosis. Furthermore, MSCs could inhibit chronic inflammation assessed by RNA-sequencing and promote gut microbiome normalization detected by 16S ribosomal RNA sequencing. CONCLUSION The results proved that MSCs could migrate to the colon, inhibit chronic inflammation, and regulate gut microbiome dysbiosis to suppress the development of CAC.
Collapse
Affiliation(s)
| | | | | | | | - Xiaohua Hou
- Division of Gastroenterology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| |
Collapse
|
|
26
|
Asl MM, Asl JM, Naghitorabi M. Comparison of the effects of olsalazine and decitabine on the expression of CDH1 and uPA genes and cytotoxicity in MDA-MB-231 breast cancer cells. Res Pharm Sci 2021; 16:278-285. [PMID: 34221061 PMCID: PMC8216162 DOI: 10.4103/1735-5362.314826] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/22/2020] [Revised: 11/28/2020] [Accepted: 04/19/2021] [Indexed: 11/29/2022] Open
Abstract
Background and purpose: Since DNA methyltransferase enzymes play a key role in DNA methylation, they can be used as a target to alter epigenetic changes and treat cancer. Recent studies have shown that olsalazine, through its potent inhibitory effect on the DNA methyltransferase enzyme, can be a good option. The aim of this study was to investigate the effects of olsalazine on cell viability and expression of CDH1 and uPA genes in MDA-MB-231 cells compared with decitabine. Experimental approach: The cytotoxicity of the drugs was determined using a standard MTT assay. MDA-MB-231 cells were treated with olsalazine and decitabine with concentrations less than IC50 to evaluate the effect of drugs on the expression of genes. RNA was extracted from the cells after 24 and 48 h and CDH1and uPA gene expression were evaluated by quantitative real-time polymerase chain reaction method. Findings/Results: The cytotoxicity of the two drugs was comparable. The IC50 values at 24 h were 4000 and 4500 μM for olsalazine and decitabine, respectively. The IC50 values of both drugs were about 300 μM at 48 h. Statistical analyzes showed a significant increase in CDH1 expression after 24-48 h treatment with olsalazine, and 48 h treatment with decitabine, without any significant increase in uPA expression. Conclusion and implications: Our results showed that olsalazine has cellular toxicity comparable to decitabine in MDA-MB-231 cells. Also compared to decitabine, olsalazine causes a greater increase in expression of CDH1 without any significant increase in uPA expression. Therefore, it appears to be a good candidate for cancer treatment.
Collapse
Affiliation(s)
- Misagh Mohammadi Asl
- Toxicology Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, I.R. Iran
| | - Javad Mohammadi Asl
- Cancer, Petroleum and Environmental Pollutants Research Center, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, I.R. Iran
| | - Mojgan Naghitorabi
- Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, I.R. Iran.,Department of Pharmacognosy, School of Pharmacy, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, I.R. Iran
| |
Collapse
|
|
27
|
Oh NS, Lee JY, Kim YT, Kim SH, Lee JH. Cancer-protective effect of a synbiotic combination between Lactobacillus gasseri 505 and a Cudrania tricuspidata leaf extract on colitis-associated colorectal cancer. Gut Microbes 2020; 12:1785803. [PMID: 32663105 PMCID: PMC7524312 DOI: 10.1080/19490976.2020.1785803] [Citation(s) in RCA: 104] [Impact Index Per Article: 20.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023] Open
Abstract
Previously, a synbiotic combination of probiotic Lactobacillus gasseri 505 (LG) and a new prebiotic, Cudrania tricuspidata leaf extract (CT) in fermented milk, designated FCT, showed an in vitro immunomodulatory effect and antioxidant activity. Although synbiotic combination might have cancer-protective effects, these activities have not been fully validated in vivo. Ten-week treatment of LG, CT, or FCT to azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colitis-associated colorectal cancer (CAC) mouse model reduced both the incidence of colonic tumors and damage to the colonic mucosa effectively, suggesting a cancer-protective effect. To understand these, biomarkers associated with inflammation, colon barrier, apoptosis, and cancer cell proliferation were monitored in AOM/DSS group versus LG/CT/FCT groups. A synbiotic combination (FCT) down-regulated pro-inflammatory cytokines (TNF-α, IFN-γ, IL-1β, and IL-6) and inflammation-associated enzymes (iNOS and COX-2), and up-regulated anti-inflammatory cytokines (IL-4 and IL-10). In addition, colon barrier experiment revealed that biomarkers of mucus layer (MUC-2 and TFF3) and tight junction (occludin and ZO-1) were up-regulated. Subsequent apoptosis experiment showed that pro-apoptotic factors (p53, p21, and Bax) were up-regulated and anti-apoptotic factors (Bcl-2 and Bcl-xL) were down-regulated. Furthermore, comparative metagenome analysis of gut microbiota revealed that Staphylococcus decreased but Lactobacillus, Bifidobacterium, and Akkermansia increased, supporting their protective effects, accompanied by increased short-chain fatty acids (SCFAs). Taken together, the FCT administration showed cancer-protective effects by reducing the risk of colitis-associated colon cancer via regulation of inflammation, carcinogenesis, and compositional change of gut microbiota. Consequently, the synbiotic combination (FCT) could be a novel potential health-protective natural agent against CAC.
Collapse
Affiliation(s)
- Nam Su Oh
- Department of Food and Biotechnology, Korea University, Sejong, South Korea
| | - Ji Young Lee
- Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea
| | - You-Tae Kim
- Department of Food Science and Biotechnology, Graduate School of Biotechnology, Kyung Hee University, Yongin, South Korea
| | - Sae Hun Kim
- Department of Biotechnology, College of Life Sciences and Biotechnology, Korea University, Seoul, South Korea,Sae Hun Kim 145 Anam-ro, Seongbuk-gu, Seoul 02841, South Korea
| | - Ju-Hoon Lee
- Department of Food Science and Biotechnology, Graduate School of Biotechnology, Kyung Hee University, Yongin, South Korea,CONTACT Ju-Hoon Lee 1732 Deogyeong-daero, Giheung-gu, Yongin-si, Gyeonggi-do 17104, South Korea
| |
Collapse
|
|
28
|
Horio Y, Uchino M, Bando T, Sasaki H, Goto Y, Kuwahara R, Minagawa T, Takesue Y, Ikeuchi H. Incidence, Risk Factors and Outcomes of Cancer of the Anal Transitional Zone in Patients with Ulcerative Colitis. J Crohns Colitis 2020; 14:1565-1571. [PMID: 32365200 DOI: 10.1093/ecco-jcc/jjaa089] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
BACKGROUND AND AIMS Performing a mucosectomy with a hand-sewn ileal pouch-anal anastomosis [IPAA] for ulcerative colitis [UC] theoretically reduces the risk of carcinoma arising from the anal transitional zone [ATZ]. Although current guidelines suggest a stapled anastomosis due to the low incidence of cancer after pouch surgery in UC patients, only a few small series have addressed the oncological advantage of mucosectomy. Therefore, we aimed to investigate the incidence of ATZ/pouch cancer. METHODS A total of 1970 UC patients who underwent surgery between April 1987 and December 2018 were included. We retrospectively analysed the incidences of primary ATZ cancer in the original operative specimen and de novo ATZ/pouch cancer after surgery. Possible risk factors for primary ATZ cancer and the pouch survival rate were assessed. RESULTS Fourteen [6.4%] primary ATZ cancers developed in 220 UC-colorectal cancer [CRC] cases. Multiple (odds ratio [OR] = 8.79, 95% confidence interval [CI] 2.77-27.83, p < 0.01) and rectal [OR = 6.48, 95% CI 1.41-29.7, p = 0.01] cancers were identified as independent risk factors for primary ATZ cancer. Four of 1970 [0.2%] patients developed de novo ATZ/pouch cancer and dysplasia. The 10-year estimated cumulative pouch survival rate was not significantly different between stapled IPAA and hand-sewn IPAA cases [95.9% and 97.3%, p = 0.25]. CONCLUSION The risk of de novo ATZ/pouch cancer and dysplasia was rare. The decision to perform a hand-sewn or a stapled IAA should be made on a case-by-case basis. However, the relatively high incidence of primary ATZ cancer in UC patients with CRC suggests that mucosectomy should be recommended for this patient group.
Collapse
Affiliation(s)
- Yuki Horio
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Motoi Uchino
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Toshihiro Bando
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Hirofumi Sasaki
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Yoshiko Goto
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Ryuichi Kuwahara
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Tomohiro Minagawa
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Hyogo, Japan
| | - Yoshio Takesue
- Infection Control and Prevention, Hyogo College of Medicine, Hyogo, Japan
| | - Hiroki Ikeuchi
- Department of Inflammatory Bowel Disease, Division of Surgery, Hyogo College of Medicine, Hyogo, Japan
| |
Collapse
|
|
29
|
Blackwell J, Saxena S, Jayasooriya N, Bottle A, Petersen I, Hotopf M, Alexakis C, Pollok RC. Prevalence and duration of gastrointestinal symptoms before diagnosis of Inflammatory Bowel Disease and predictors of timely specialist review: a population-based study. J Crohns Colitis 2020; 15:jjaa146. [PMID: 32667962 DOI: 10.1093/ecco-jcc/jjaa146] [Citation(s) in RCA: 34] [Impact Index Per Article: 6.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2020] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Lack of timely referral and significant waits for specialist review amongst individuals with unresolved gastrointestinal (GI) symptoms can result in delayed diagnosis of Inflammatory Bowel Disease (IBD). AIMS To determine the frequency and duration of GI symptoms and predictors of timely specialist review before the diagnosis of both Crohn's Disease (CD) and ulcerative colitis (UC). METHODS Case-control study of IBD matched 1:4 for age and sex to controls without IBD using the Clinical Practice Research Datalink from 1998-2016. RESULTS We identified 19,555 cases of IBD, and 78,114 controls. 1 in 4 cases of IBD reported gastrointestinal symptoms to their primary care physician more than 6 months before receiving a diagnosis. There is a significant excess prevalence of GI symptoms in each of the 10 years before IBD diagnosis. GI symptoms were reported by 9.6% and 10.4% at 5 years before CD and UC diagnosis respectively compared to 5.8% of controls. Amongst patients later diagnosed with IBD, <50% received specialist review within 18 months from presenting with chronic GI symptoms. Patients with a previous diagnosis of irritable bowel syndrome or depression were less likely to receive timely specialist review (IBS: HR=0.77, 95%CI 0.60-0.99, depression: HR=0.77, 95%CI 0.60-0.98). CONCLUSIONS There is an excess of GI symptoms 5 years before diagnosis of IBD compared to the background population which are likely attributable to undiagnosed disease. Previous diagnoses of IBS and depression are associated with delays in specialist review. Enhanced pathways are needed to accelerate specialist referral and timely IBD diagnosis.
Collapse
Affiliation(s)
- J Blackwell
- Dept. Gastroenterology, St George's Healthcare NHS Trust, St George's University London, UK
| | - S Saxena
- School of Public Health, Imperial College London, London, UK
| | - N Jayasooriya
- Dept. Gastroenterology, St George's Healthcare NHS Trust, St George's University London, UK
| | - A Bottle
- School of Public Health, Imperial College London, London, UK
| | - I Petersen
- Dept. Primary Care and Population Health, University College London, London, UK
- Dept. Clinical Epidemiology, Aarhus University, Denmark
| | - M Hotopf
- Institute of Psychiatry, Kings College London, London, UK
- South London and Maudsley NHS Foundation Trust, London, UK
| | - C Alexakis
- Dept. Gastroenterology, St George's Healthcare NHS Trust, St George's University London, UK
| | - R C Pollok
- Dept. Gastroenterology, St George's Healthcare NHS Trust, St George's University London, UK
| |
Collapse
|
|
30
|
A Nucleotide Analog Prevents Colitis-Associated Cancer via Beta-Catenin Independently of Inflammation and Autophagy. Cell Mol Gastroenterol Hepatol 2020; 11:33-53. [PMID: 32497793 PMCID: PMC7593585 DOI: 10.1016/j.jcmgh.2020.05.012] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/25/2020] [Revised: 05/26/2020] [Accepted: 05/27/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Chronic bowel inflammation increases the risk of colon cancer; colitis-associated cancer (CAC). Thiopurine treatments are associated with a reduction in dysplasia and CAC in inflammatory bowel disease (IBD). Abnormal Wnt/β-catenin signalling is characteristic of >90% of colorectal cancers. Immunosuppression by thiopurines is via Rac1 GTPase, which also affects Wnt/β-catenin signalling. Autophagy is implicated in colonic tumors, and topical delivery of the thiopurine thioguanine (TG) is known to alleviate colitis and augment autophagy. This study investigated the effects of TG in a murine model of CAC and potential mechanisms. METHODS Colonic dysplasia was induced by exposure to azoxymethane (AOM) and dextran sodium sulfate (DSS) in wild-type (WT) mice and mice harboring intestinal epithelial cell-specific deletion of autophagy related 7 gene (Atg7ΔIEC). TG or vehicle was administered intrarectally, and the effect on tumor burden and β-catenin activity was assessed. The mechanisms of action of TG were investigated in vitro and in vivo. RESULTS TG ameliorated DSS colitis in wild-type but not Atg7ΔIEC mice, demonstrating that anti-inflammatory effects of locally delivered TG are autophagy-dependent. However, TG inhibited CAC in both wild-type and Atg7ΔIEC mice. This was associated with decreased β-catenin activation/nuclear translocation demonstrating that TG's inhibition of tumorigenesis occurred independently of anti-inflammatory and pro-autophagic actions. These results were confirmed in cell lines, and the dependency on Rac1 GTPase was demonstrated by siRNA knockdown and overexpression of constitutively active Rac1. CONCLUSIONS Our findings provide evidence for a new mechanism that could be exploited to improve CAC chemoprophylactic approaches.
Collapse
|
|
31
|
Kuai Y, Liu H, Liu D, Liu Y, Sun Y, Xie J, Sun J, Fang Y, Pan H, Han W. An ultralow dose of the NADPH oxidase inhibitor diphenyleneiodonium (DPI) is an economical and effective therapeutic agent for the treatment of colitis-associated colorectal cancer. Am J Cancer Res 2020; 10:6743-6757. [PMID: 32550901 PMCID: PMC7295061 DOI: 10.7150/thno.43938] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/14/2020] [Accepted: 05/11/2020] [Indexed: 12/31/2022] Open
Abstract
Long-term inflammatory stimulation is considered one of the most important causes of colorectal cancer. Diphenyleneiodonium (DPI), an NADPH oxidase inhibitor, can inhibit a variety of inflammatory responses. However, the systemic toxicity of DPI limits its clinical application. Whether DPI can inhibit colitis-associated colorectal cancer (CAC) at ultralow concentrations remains unknown. Methods: CAC was induced by azoxymethane (AOM) injection followed by treatment with dextran sulfate sodium (DSS), and DPI was intraperitoneally injected (i.p.) in the first cycle for 21 days. Colon tissue was collected and analyzed by western blotting. Immune cell infiltration and macrophage polarization were examined by immunohistochemistry, immunofluorescence, or real-time polymerase-chain reaction (PCR). Reactive oxygen species (ROS) production was measured by flow cytometry. Results: Ultralow dose DPI significantly ameliorated the DSS-induced colitis and attenuated the colon tumorigenesis in the mouse model of AOM/ DSS-induced CAC. Mechanistically, an ultralow dose of DPI inhibited the production of pro-inflammatory cytokines, (tumor necrosis factor (TNF)-α and interleukin (IL)-6), reduced the macrophage infiltration and classical polarization, and induced the ROS generation. These effects were found to be related to the inhibition of the phosphorylation of signal transducer and activator of transcription 3 (STAT3), mitogen-activated protein kinase (MAPK), and nuclear factor kappa B (NF -κB). Conclusion: The present study revealed that an ultralow dose of DPI, with no significant systemic toxicity involved, may be an effective way to prevent the occurrence and development of CAC.
Collapse
|
|
32
|
The Role of MicroRNAs upon Epithelial-to-Mesenchymal Transition in Inflammatory Bowel Disease. Cells 2019; 8:cells8111461. [PMID: 31752264 PMCID: PMC6912477 DOI: 10.3390/cells8111461] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2019] [Revised: 11/03/2019] [Accepted: 11/18/2019] [Indexed: 02/06/2023] Open
Abstract
Increasing evidence suggest the significance of inflammation in the progression of cancer, for example the development of colorectal cancer in Inflammatory Bowel Disease (IBD) patients. Long-lasting inflammation in the gastrointestinal tract causes serious systemic complications and breaks the homeostasis of the intestine, where the altered expression of regulatory genes and miRNAs trigger malignant transformations. Several steps lead from acute inflammation to malignancies: epithelial-to-mesenchymal transition (EMT) and inhibitory microRNAs (miRNAs) are known factors during multistage carcinogenesis and IBD pathogenesis. In this review, we outline the interactions between EMT components and miRNAs that may affect cancer development during IBD.
Collapse
|
|
33
|
Koh SJ, Kim JW, Kim BG, Lee KL, Kim DW, Kim JS. Matricellular protein periostin promotes colitis-associated colon tumorigenesis in mice. Carcinogenesis 2019; 40:102-111. [PMID: 30204842 DOI: 10.1093/carcin/bgy120] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/15/2018] [Revised: 08/27/2018] [Accepted: 09/07/2018] [Indexed: 12/28/2022] Open
Abstract
Periostin is expressed in inflamed colonic mucosa and colon cancer tissue; however, its role in the development of colitis-associated colon cancer (CAC) remains unclear. Wild-type and periostin-deficient (Postn-/-) mice were given a single intraperitoneal injection of azoxymethane at 12.5 mg/kg on day 0. Seven days later, 2% dextran sulfate sodium (DSS) was administered via drinking water for 5 days, followed by untreated, free water consumption for 16 days. This cycle was repeated three times. In vitro assays were performed using COLO205 and HCT116 cells. Small interfering RNA was used to inhibit Postn gene translation. Periostin expression was determined using colon samples from patients with CAC. Postn-/- mice exhibited lower tumor burden compared with wild-type mice. Exposure to azoxymethane/DSS resulted in extensive epithelial apoptosis in Postn-/- mice compared with that in wild-type mice. In addition, immunoreactivity for IκB kinase, β-catenin and COX2 was markedly reduced in Postn-/- mice. Expression of interleukin (IL)-1β and tumor necrosis factor α (TNF-α) significantly decreased, whereas that of IL-10 and transforming growth factor β (TGF-β) increased in peritoneal macrophages isolated from Postn-/- mice. Silencing of the Postn gene resulted in reduced cell viability, which was associated with caspase-3 activation, and this was reversed by treatment with recombinant periostin. Knockdown of Postn downregulated bcl-2, cIAP1, cFLIP-L, VEGF, Axin 2 and cyclin D1, and upregulated bak expression. Periostin expression was significantly increased in patients with CAC. Periostin aggravates CAC development, which suggests that periostin is a potential therapeutic target for the prevention of CAC in patients with inflammatory bowel disease.
Collapse
Affiliation(s)
- Seong-Joon Koh
- Department of Internal Medicine, Division of Gastroenteology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Ji Won Kim
- Department of Internal Medicine, Division of Gastroenteology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Byeong Gwan Kim
- Department of Internal Medicine, Division of Gastroenteology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Kook Lae Lee
- Department of Internal Medicine, Division of Gastroenteology, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Dae Woo Kim
- Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University Boramae Hospital, Seoul National University College of Medicine, Seoul, Korea
| | - Joo Sung Kim
- Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.,Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| |
Collapse
|
|
34
|
Huang R, Wang K, Gao L, Gao W. TIMP1 Is A Potential Key Gene Associated With The Pathogenesis And Prognosis Of Ulcerative Colitis-Associated Colorectal Cancer. Onco Targets Ther 2019; 12:8895-8904. [PMID: 31802901 PMCID: PMC6826183 DOI: 10.2147/ott.s222608] [Citation(s) in RCA: 20] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/09/2019] [Accepted: 10/09/2019] [Indexed: 12/24/2022] Open
Abstract
Purpose Colorectal cancer (CRC) is the third most frequently diagnosed cancer worldwide. As a high-risk factor for CRC, ulcerative colitis (UC) has been demonstrated to lead to epithelial dysplasia, DNA damage, and eventually cancer. There are approximately 18% of patients with UC may develop CRC. Patients and methods The gene expression profiles were retrieved from the Gene Expression Omnibus. The Database for Annotation, Visualization and Integrated Discovery was employed to conduct gene annotations. Protein-protein interaction network was constructed by the Search Tool for the Retrieval of Interacting Genes, and further analysed by the Molecular Complex Detection. The correlation between TIMP1 and prognosis was evaluated by the Gene Expression Profiling Interactive Analysis. To predict the potential functions of TIMP1, the GeneMANIA, Coremine, and FunRich were employed. After transfection with small interfering RNA targeting TIMP1, cell proliferation, migration, and apoptosis were determined by CCK-8, scratch wound, and Annexin V-FITC/PI assays, respectively. Results TIMP1, consistently overexpressed in the initiation and progression of UC-associated CRC (ucaCRC), was identified to be a potential biomarker for the prognosis of patients with CRC. Experimental results showed knockdown of TIMP1 could increase the migration, while did not affect the proliferation and apoptosis of RKO cells. The role of TIMP1 in the malignant transformation of ucaCRC was confirmed by using the protein/gene interactions and biological process annotation and validated by analysing the transcription factors targeting TIMP1. Conclusion TIMP1 is consistently upregulated in the pathological process of ucaCRC and can be a potential biomarker for the worse prognosis of CRC.
Collapse
Affiliation(s)
- Ru Huang
- Department of Heart Failure, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Kaijing Wang
- Department of Colorectal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Lei Gao
- Department of Heart Failure, Research Center for Translational Medicine, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
| | - Wei Gao
- Department of Colorectal Surgery, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People's Republic of China
| |
Collapse
|
|
35
|
Choi YI, Kim TJ, Park DK, Chung JW, Kim KO, Kwon KA, Kim YJ. Comparison of outcomes of continuation/discontinuation of 5-aminosalicylic acid after initiation of anti-tumor necrosis factor-alpha therapy in patients with inflammatory bowel disease. Int J Colorectal Dis 2019; 34:1713-1721. [PMID: 31471699 DOI: 10.1007/s00384-019-03368-1] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 08/16/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND Few maintenance therapeutic options are available for inflammatory bowel disease (IBD). Data on the effects of continuing 5-aminosalicylic acid (5-ASA) treatment in patients who commence on biologics as maintenance treatment remain scarce. We evaluated IBD patient outcomes after continuation/discontinuation of 5-ASA when biologics were administered as maintenance treatment. METHODS We retrospectively reviewed the clinical, laboratory, and imaging data of patients diagnosed with IBD (ulcerative colitis (UC), 763; Crohn's disease (CD), 537) in the Gil Medical Center (GMC) from February 2005 to June 2018. We divided patients administered with biologics as maintenance treatment into those who did and did not continue on 5-ASA and compared the efficacies of the two treatment options using the log-rank test and Cox proportional hazards models. RESULTS Of 1300 total IBD patients, 128 (UC, 63; CD, 65) were prescribed biologics as induction and maintenance treatments. The median follow-up period was 109.5 weeks. All cases were divided into those who did or did not combine 5-ASA with biologics as maintenance treatments. Kaplan-Meier analysis showed that the event-free survival (exacerbation of disease activity) of UC patients treated with biologics and 5-ASA (n = 42) was not significantly lower than that of those taking biologics alone (n = 21) (log rank test, P = 0.68). The same was true of CD patients (n = 42, biologics and 5-ASA; n = 23, biologics only) (log rank test, P = 0.87). CONCLUSIONS Continuation of 5-ASA after initiation of anti-tumor necrosis factor-alpha agents did not improve prognosis in Korean IBD patients compared with that of those who discontinued 5-ASA during maintenance treatment, particularly in patients who experienced more than two disease aggravations.
Collapse
Affiliation(s)
- Youn I Choi
- Department of Gastroenterology, Gil Medical Center, Gachon University, 405-760 1198 Guwol dong, Namdong-gu, Incheon, South Korea
| | - Tae Jun Kim
- Department of Gastroenterology, Gil Medical Center, Gachon University, 405-760 1198 Guwol dong, Namdong-gu, Incheon, South Korea
| | - Dong Kyun Park
- Department of Gastroenterology, Gil Medical Center, Gachon University, 405-760 1198 Guwol dong, Namdong-gu, Incheon, South Korea
| | - Jun-Won Chung
- Department of Gastroenterology, Gil Medical Center, Gachon University, 405-760 1198 Guwol dong, Namdong-gu, Incheon, South Korea
| | - Kyoung Oh Kim
- Department of Gastroenterology, Gil Medical Center, Gachon University, 405-760 1198 Guwol dong, Namdong-gu, Incheon, South Korea
| | - Kwang An Kwon
- Department of Gastroenterology, Gil Medical Center, Gachon University, 405-760 1198 Guwol dong, Namdong-gu, Incheon, South Korea
| | - Yoon Jae Kim
- Department of Gastroenterology, Gil Medical Center, Gachon University, 405-760 1198 Guwol dong, Namdong-gu, Incheon, South Korea.
| |
Collapse
|
|
36
|
Blackwell J, Saxena S, Alexakis C, Bottle A, Cecil E, Majeed A, Pollok RC. The impact of smoking and smoking cessation on disease outcomes in ulcerative colitis: a nationwide population-based study. Aliment Pharmacol Ther 2019; 50:556-567. [PMID: 31389044 DOI: 10.1111/apt.15390] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2019] [Revised: 03/29/2019] [Accepted: 06/06/2019] [Indexed: 12/19/2022]
Abstract
BACKGROUND Smokers are less likely to develop ulcerative colitis (UC) but the impact of smoking and subsequent cessation on clinical outcomes in UC is unclear. AIM To evaluate the effect of smoking status and smoking cessation on disease outcomes. METHODS Using a nationally representative clinical research database, we identified incident cases of UC during 2005-2016. Patients were grouped as never-smokers, ex-smokers and smokers based on smoking status recorded in the 2 years preceding UC diagnosis. We defined subgroups of persistent smokers and smokers who quit within 2 years after diagnosis. We compared the rates of overall corticosteroid use, corticosteroid-requiring flares, corticosteroid dependency, thiopurine use, hospitalisation and colectomy between these groups. RESULTS We identified 6754 patients with a new diagnosis of UC over the study period with data on smoking status, of whom 878 were smokers at diagnosis. Smokers had a similar risk of corticosteroid-requiring flares (OR 1.16, 95% CI 0.92-1.25), thiopurine use (HR 0.84, 95% CI 0.62-1.14), corticosteroid dependency (HR 0.85, 95% CI 0.60-1.11), hospitalisation (HR 0.92, 95% CI 0.72-1.18) and colectomy (HR 0.78, 95% CI 0.50-1.21) in comparison with never-smokers. Rates of flares, thiopurine use, corticosteroid dependency, hospitalisation and colectomy were not significantly different between persistent smokers and those who quit smoking after a diagnosis of UC. CONCLUSIONS Smokers and never-smokers with UC have similar outcomes with respect to flares, thiopurine use, corticosteroid dependency, hospitalisation and colectomy. Smoking cessation was not associated with worse disease course. The risks associated with smoking outweigh any benefits. UC patients should be counselled against smoking.
Collapse
Affiliation(s)
- Jonathan Blackwell
- Department of Gastroenterology, St George's Healthcare NHS Trust and St George's University, London, UK
| | - Sonia Saxena
- School of Public Health, Imperial College London, London, UK
| | - Christopher Alexakis
- Department of Gastroenterology, St George's Healthcare NHS Trust and St George's University, London, UK
| | - Alex Bottle
- School of Public Health, Imperial College London, London, UK
| | - Elizabeth Cecil
- School of Public Health, Imperial College London, London, UK
| | - Azeem Majeed
- School of Public Health, Imperial College London, London, UK
| | - Richard C Pollok
- Department of Gastroenterology, St George's Healthcare NHS Trust and St George's University, London, UK
| |
Collapse
|
|
37
|
Li W, Zhao X, Lv X, Han W, Wang H. Silibinin Retards Colitis-associated Carcinogenesis by Repression of Cdc25C in Mouse Model. Inflamm Bowel Dis 2019; 25:1187-1195. [PMID: 30753481 DOI: 10.1093/ibd/izz007] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Indexed: 02/07/2023]
Abstract
PURPOSE Silibinin possesses the efficacy of anticancer and anti-inflammation. We aimed to test whether silibinin could prevent colitis-associated carcinogenesis in mouse model. EXPERIMENTAL DESIGN Azoxymethane (AOM) and dextran sulfate sodium (DSS) were used to induce colitis-associated tumorigenesis in C57BL mice. Six-to-eight-week-old male mice were gavaged with 350 or 750 mg/kg of silibinin for 10 weeks right after DSS administration. The mice were then sacrificed, and colon tissues were measured for tumor multiplicity and size. Molecular changes about proliferation, apoptosis and inflammation were tested. RESULTS Silibinin feeding showed a dose-dependent inhibition on the size of tumor induced by AOM/DSS in mice. In addition, silibinin inhibited cell proliferation evidenced by a decrease (P < 0.05) in Ki-67 and proliferating cell nuclear antigen (PCNA). However, silibinin did not show any significant effect on inflammation, apoptosis, and the mRNA expression of cyclooxygenase-2 (COX-2), inducible nitric oxide synthase (iNOS), and vascular endothelial growth factor (VEGF). The experiments in vitro showed that silibinin induced cell cycle arrest at G2/M phase in CT-26 cells, a mouse colonic cancer cell line. Furthermore, silibinin reduced the expression of Cdc25C and blocked the dephosphorylation of CDK1 at multiple sites both in vitro and in vivo. CONCLUSIONS Silibinin targets Cdc25C/CDK1 pathway and mitigates colitis-associated tumorigenesis in mice. Thus, our findings indicate the chemopreventive potential of silibinin for inflammation-associated colon cancer.
Collapse
Affiliation(s)
- Weiwei Li
- State Key Laboratory of Molecular Oncology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xinhua Zhao
- State Key Laboratory of Molecular Oncology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Xue Lv
- State Key Laboratory of Molecular Oncology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Wenxiao Han
- State Key Laboratory of Molecular Oncology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hongying Wang
- State Key Laboratory of Molecular Oncology, National Cancer Center/ National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| |
Collapse
|
|
38
|
Ballester MP, Marti-Aguado D, Fullana M, Bosca-Watts MM, Tosca J, Romero E, Sanchez A, Navarro-Cortes P, Anton R, Mora F, Minguez M. Impact and risk factors of non-adherence to 5-aminosalicylates in quiescent ulcerative colitis evaluated by an electronic management system. Int J Colorectal Dis 2019; 34:1053-1059. [PMID: 30963247 DOI: 10.1007/s00384-019-03271-9] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 02/21/2019] [Indexed: 02/04/2023]
Abstract
BACKGROUND AND OBJECTIVE To determine the impact of non-adherence to 5-Aminosalicylates (5-ASA) on the risk of flares and to identify risk factors of non-adherence. METHODS Observational, cohort study of ulcerative colitis (UC) patients in clinical remission at least 6 months on 5-ASA monotherapy maintenance prescribed by an electronic management program. Adherence was considered when 80% of the prescribed 5-ASA had been dispensed at the pharmacy. The study analyzed the existence and degree of 5-ASA adherence, disease course, UC phenotypic expression, and 5-ASA dose and regimen, and consumption of non-UC chronic drugs during 2-year follow-up. RESULTS The study included 274 patients, 49% males with a median age of 38 (27-49) years old. Overall, 41% of patients were non-adherent to 5-ASA. Risk of flares was reduced in the adherent group (36% vs 54%; OR = 0,484; p = 0,004), mainly the mild ones (26% vs 38%; OR = 0,559; p = 0,031). Non-adherence was associated with younger age at diagnosis (32 (26-45) vs 41.5 (21-50), p = 0.000) and no-consumption of other chronic treatments (1.1 vs 2.1; OR = 1709; p = 0,048). CONCLUSION Non-adherence to 5-ASA evaluated by the pharmaceutical management system was at 41% with a higher risk of relapse. Younger patients and patients who do not receive non-UC chronic treatments showed lower adherence rate.
Collapse
Affiliation(s)
- M P Ballester
- IBD Unit, Digestive Disease Department, University Clinic Hospital of Valencia, University of Valencia, Blasco Ibañez Av. 17, 46010, Valencia, Spain
| | - D Marti-Aguado
- IBD Unit, Digestive Disease Department, University Clinic Hospital of Valencia, University of Valencia, Blasco Ibañez Av. 17, 46010, Valencia, Spain.
| | - M Fullana
- University of Valencia, Valencia, Spain
| | - M M Bosca-Watts
- IBD Unit, Digestive Disease Department, University Clinic Hospital of Valencia, University of Valencia, Blasco Ibañez Av. 17, 46010, Valencia, Spain
| | - J Tosca
- IBD Unit, Digestive Disease Department, University Clinic Hospital of Valencia, University of Valencia, Blasco Ibañez Av. 17, 46010, Valencia, Spain
| | - E Romero
- IBD Unit, Digestive Disease Department, University Clinic Hospital of Valencia, University of Valencia, Blasco Ibañez Av. 17, 46010, Valencia, Spain
| | - A Sanchez
- IBD Unit, Digestive Disease Department, University Clinic Hospital of Valencia, University of Valencia, Blasco Ibañez Av. 17, 46010, Valencia, Spain
| | - P Navarro-Cortes
- IBD Unit, Digestive Disease Department, University Clinic Hospital of Valencia, University of Valencia, Blasco Ibañez Av. 17, 46010, Valencia, Spain
| | - R Anton
- IBD Unit, Digestive Disease Department, University Clinic Hospital of Valencia, University of Valencia, Blasco Ibañez Av. 17, 46010, Valencia, Spain
| | - F Mora
- IBD Unit, Digestive Disease Department, University Clinic Hospital of Valencia, University of Valencia, Blasco Ibañez Av. 17, 46010, Valencia, Spain.,University of Valencia, Valencia, Spain
| | - M Minguez
- IBD Unit, Digestive Disease Department, University Clinic Hospital of Valencia, University of Valencia, Blasco Ibañez Av. 17, 46010, Valencia, Spain.,University of Valencia, Valencia, Spain
| |
Collapse
|
|
39
|
Waljee AK, Chaisidhivej N, Saini SD, Higgins PDR. De-escalation of IBD Therapy: When, Who, and How? CROHN'S & COLITIS 360 2019. [DOI: 10.1093/crocol/otz008] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Abstract
When patients with inflammatory bowel disease reach clinical remission with biologic therapy, a question that often comes up is, “when can I stop my biologic medication?” This is a question fraught with challenges for both physicians and patients. For physicians, there are valid concerns that stepping down from a successful therapy will lead to relapse and disease exacerbation, and that stepping down could lead to anti-biologic antibodies. For patients, the question is often driven by concerns about long-term side effects and costs of biologics. This review provides an overview of the rationale for, and risks of, withdrawal of IBD therapy. Selected studies have shown how to identify subsets of patients in whom de-escalation can be performed with low risk of relapse. Practical guidance on when and how to de-escalate IBD therapy is provided.
Collapse
Affiliation(s)
- Akbar K Waljee
- From VA Center for Clinical Management Research, Ann Arbor, MI
- University of Michigan Medical School, Institute for Healthcare Policy and Innovation, Ann Arbor, MI
- University of Michigan Medical School, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Ann Arbor, MI
| | | | - Sameer D Saini
- From VA Center for Clinical Management Research, Ann Arbor, MI
- University of Michigan Medical School, Institute for Healthcare Policy and Innovation, Ann Arbor, MI
- University of Michigan Medical School, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Ann Arbor, MI
| | - Peter D R Higgins
- University of Michigan Medical School, Department of Internal Medicine, Division of Gastroenterology and Hepatology, Ann Arbor, MI
| |
Collapse
|
|
40
|
Abstract
Unexplained iron-deficiency anemia is an important marker for colorectal cancer (CRC). Our objectives were as follows: (a) to assess whether the association between anemia and CRC can be detected on the 'Clinical Practice Research Datalink', (b) to evaluate the timing between laboratory changes and CRC detection, and (c) to analyze its association with survival. We conducted a case-control study on patients with an incident CRC diagnosis during 2008-2012 and a 1 : 1-matched control group. We compared anemia markers serum ferritin (SF), hemoglobin (Hb), mean corpuscular volume (MCV), and red blood cell count between cases and controls using conditional logistic regression. We assessed survival in CRC cases. SF values up to 20 ng/ml were associated with an odds ratio [OR (95% confidence interval)] of 10.66 (6.88-16.51) compared with SF values of 101-300 ng/ml when restricted to measurements up to 180 days before the CRC diagnosis. For measurements taken at 1 year or earlier before the diagnosis, the OR was 2.02 (1.57-2.61). For Hb values less than 9 g/dl compared with Hb values of 13.0-15.9 g/dl the corresponding ORs were 74.25 (34.69-158.91) and 2.19 (1.31-3.67), respectively. The corresponding ORs for MCV values up to 80 fl compared with MCV values of 86-95 fl were 13.94 (10.31-18.85) and 1.89 (1.51-2.36), respectively. Low levels of these markers were only weakly associated with survival. Hb, MCV, and SF levels substantially dropped only shortly before the CRC diagnosis. Although slightly more cases had anemia markers compared with controls at 1 year or earlier before the diagnosis, most cases still had normal values. The Clinical Practice Research Datalink is well-suited to detect associations between low Hb, MCV, and SF levels and CRC.
Collapse
|
|
41
|
Effect of Long-Term Mesalamine Therapy on Cancer-Associated Gene Expression in Colonic Mucosa of Patients with Ulcerative Colitis. Dig Dis Sci 2019; 64:740-750. [PMID: 30478770 DOI: 10.1007/s10620-018-5378-8] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2018] [Accepted: 11/13/2018] [Indexed: 01/20/2023]
Abstract
BACKGROUND The role of 5-aminosalicylic acid (5-ASA or mesalamine) in the prevention of colorectal cancer in ulcerative colitis (UC) patients was reported, but the effect on molecular targets in UC colon mucosa is unknown. AIM This observational study evaluates gene expression levels of 5-ASA targets using serial colon biopsy specimens from UC patients undergoing long-term 5-ASA therapy. METHODS Transcript levels were compared between colonoscopic biopsy specimens collected from 62 patients at initial and final follow-up colonoscopy at 2-6 years. All patients had mild-to-moderate UC and were undergoing long-term 5-ASA maintenance. Stepwise multiple linear regression analyses were performed to correlate changes in transcript levels with therapeutic response (Mayo clinical score endoscopy and DAI and/or Nancy histopathology score) and nonclinical variables. RESULTS The transcript levels of colorectal carcinogenesis-associated known 5-ASA target genes were significantly reduced after prolonged 5-ASA therapy (P < 0.005-0.03). Multiple linear regression models predicted significant association between transcript levels of Ki-67, NF-kB (p65), PPARγ, COX-2 and IL-8, CDC25A, and CXCL10 with duration of drug (5-ASA) exposure (P ≤ 0.05). Ki-67, NF-kB (p65), and CXCL10 transcripts were also correlated with reduced endoscopy sub-score (P ≤ 0.05). COX-2, IL-8, CDC25A, and TNF transcripts strongly correlated with DAI sub-scores (P ≤ 0.05). Only COX-2 and IL-8 transcript levels correlated (P ≤ 0.05) with Nancy histological score. CONCLUSION This study provides molecular evidence of changes in carcinogenesis-related targets/pathways in colon tissue during long-term 5-ASA maintenance therapy that may contribute to the observed chemopreventive effects of 5-ASA in UC patients.
Collapse
|
|
42
|
Yousefi‐Ahmadipour A, Rashidian A, Mirzaei MR, Farsinejad A, PourMohammadi‐Nejad F, Ghazi‐Khansari M, Ai J, Shirian S, Allahverdi A, Saremi J, Ebrahimi‐Barough S. Combination therapy of mesenchymal stromal cells and sulfasalazine attenuates trinitrobenzene sulfonic acid induced colitis in the rat: The S1P pathway. J Cell Physiol 2018; 234:11078-11091. [DOI: 10.1002/jcp.27944] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/10/2018] [Accepted: 10/25/2018] [Indexed: 12/15/2022]
Affiliation(s)
- Aliakbar Yousefi‐Ahmadipour
- Department of Tissue Engineering and Applied Cell Sciences School of Advanced Technologies in Medicine, Tehran University of Medical Sciences Tehran Iran
| | - Amir Rashidian
- Department of Pharmacology School of Medicine, Tehran University of Medical Sciences Tehran Iran
| | - Mohammad Reza Mirzaei
- Department of Clinical Biochemistry Faculty of Medicine Rafsanjan University of Medical Sciences Rafsanjan Iran
| | - Alireza Farsinejad
- Department of Hematology and Laboratory Sciences Faculty of Allied Medicine, Kerman University of Medical Sciences Kerman Iran
| | - Fatemeh PourMohammadi‐Nejad
- Department of Periodontics School of Dentistry, Rafsanjan University of Medical Sciences, Rafsanjan Kerman Iran
| | - Mahmoud Ghazi‐Khansari
- Department of Pharmacology School of Medicine, Tehran University of Medical Sciences Tehran Iran
| | - Jafar Ai
- Department of Tissue Engineering and Applied Cell Sciences School of Advanced Technologies in Medicine, Tehran University of Medical Sciences Tehran Iran
| | - Sadegh Shirian
- Department of Pathology School of Veterinary Medicine, Shahrekord University Shahrekord Iran
| | - Amir Allahverdi
- Department of Tissue Engineering and Applied Cell Sciences School of Advanced Technologies in Medicine, Tehran University of Medical Sciences Tehran Iran
| | - Jamileh Saremi
- Department of Tissue Engineering and Applied Cell Sciences School of Advanced Technologies in Medicine, Tehran University of Medical Sciences Tehran Iran
| | - Somayeh Ebrahimi‐Barough
- Department of Tissue Engineering and Applied Cell Sciences School of Advanced Technologies in Medicine, Tehran University of Medical Sciences Tehran Iran
| |
Collapse
|
|
43
|
Non-aspirin non-steroidal anti-inflammatory drugs in prevention of colorectal cancer in people aged 40 or older: A systematic review and meta-analysis. Cancer Epidemiol 2018; 58:52-62. [PMID: 30472477 DOI: 10.1016/j.canep.2018.11.002] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/31/2018] [Revised: 10/13/2018] [Accepted: 11/08/2018] [Indexed: 02/07/2023]
Abstract
There is still insufficient data about the risk-benefit profile about recommending non-aspirin, non-steroidal anti-inflammatory drugs (NA-NSAIDs) for colorectal cancer (CRC) prevention, especially in people aged 40 years or older. This study specifically addressed the association between regular NA-NSAIDs use and CRC risk in the population aged 40 years or older, performing a comprehensive systematic review and meta-analysis of all published studies on this topic until April 2018, by a search of PubMed, Scopus and Web of science databases and clinical trial registries. Two reviewers independently selected studies based on predefined inclusion criteria and assessed study quality using the Newcastle-Otawa scale. The data was combined with the random effects model. Potential heterogeneity was calculated as Q statistic and I2 value. A total of 23 studies involving more than 1 million subjects contributed to the analysis. Pooled odds ratio (OR) of NA-NSAIDs effects on CRC risk was 0.74 (0.67-0.81), I2 = 75.9%, p < 0.001. Heterogeneity was explained by a number of variables including the quality of the studies. Significant protective effects of NA-NSAIDs use were found for women (risk reduction of 19%), higher doses (risk reduction of 18%), distal colon cancer (risk reduction of 22%) and white people (risk reduction from 31% to 41%). From the results NA-NSAIDs use appears to be CRC chemopreventive for a specific subgroup of the population.
Collapse
|
|
44
|
Smoking Status at Diagnosis and Subsequent Smoking Cessation: Associations With Corticosteroid Use and Intestinal Resection in Crohn's Disease. Am J Gastroenterol 2018; 113:1689-1700. [PMID: 30323269 DOI: 10.1038/s41395-018-0273-7] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/15/2018] [Accepted: 07/31/2018] [Indexed: 02/07/2023]
Abstract
BACKGROUND The impact of smoking at diagnosis and subsequent smoking cessation on clinical outcomes in Crohn's disease (CD) has not been evaluated in a population-based cohort. METHODS Using a nationally representative clinical research database, we identified incident cases of CD between 2005 and 2014. We compared the following outcomes: overall corticosteroid (CS) use; flares requiring CS; CS dependency and intestinal surgery between smokers and non-smokers at time of CD diagnosis. Differences in these outcomes were also compared between persistent smokers and smokers who quit within 2 years of diagnosis. RESULTS We identified 3553 patients with a new CD diagnosis over the study period of whom 1121 (32%) were smokers. Smokers at CD diagnosis had significantly higher CS-use (56 versus 47%, p < 0.0001), proportionally more CS flares (>1 CS flare/year: 9 versus 6%, p < 0.0001), and higher CS dependency (27 versus 21%, p < 0.0001) than non-smokers. Regression analysis identified smoking at diagnosis to be associated with a higher risk of intestinal surgery (HR 1.64, 95% CI 1.16-2.52). There was a significantly higher proportion of 'quitters' who remained steroid-free through follow-up in comparison to 'persistent smokers' (45.4 versus 37.5%, respectively, p = 0.02). 'Quitters' also had lower rates of CS dependency compared to 'persistent smokers' (24 versus 33%, p = 0.008). CONCLUSIONS Smokers at CD diagnosis have higher CS-use, CS dependency and higher risk of intestinal surgery. Quitting smoking appears to have beneficial effects on disease related outcomes, including reducing CS dependency highlighting the importance of offering early smoking cessation support.
Collapse
|
|
45
|
Ma C, Ascoytia C, McCarrier KP, Martin M, Feagan BG, Jairath V. Physicians' Perspectives on Cost, Safety, and Perceived Efficacy Determine Aminosalicylate Use in Crohn's Disease. Dig Dis Sci 2018; 63:2555-2563. [PMID: 29959726 DOI: 10.1007/s10620-018-5181-6] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2018] [Accepted: 06/22/2018] [Indexed: 02/08/2023]
Abstract
BACKGROUND Aminosalicylates are the most commonly prescribed therapy in Crohn's disease (CD), despite uncertainty in the evidence to support their efficacy. AIMS To examine physicians' perspectives on aminosalicylate use for CD and explore the discordance between clinical practice and the evidence base. METHODS A qualitative interview study was performed amongst physicians with at least 4 years of independent experience in managing CD patients. Semi-structured telephone interviews were conducted using an exploratory interview guide. Interview transcripts were thematically analyzed to elucidate concepts pertaining to treatment strategies for CD, motivations for prescribing aminosalicylates, perceived benefits and harms of aminosalicylate use, and the relationship between the evidence and real-world prescribing practices. RESULTS A representative sample of thirty physicians from four different countries and multiple practice environments (university/teaching hospitals, public practice, private/community practice, and subspecialty gastroenterology clinics) participated. Nearly all physicians (93.3%, 28/30) reported prescribing aminosalicylates for CD. Aminosalicylates were endorsed as first-line therapy for mild CD by nearly half of participants (13/30, 43.3%). A favorable safety profile, possible efficacy in mild colonic CD, and patient reluctance to step-up to other therapies were primary motivators for aminosalicylate use. Almost half of respondents (46.7%) expressed that the evidence informing aminosalicylate efficacy in CD differed substantially from their own clinical experience. CONCLUSIONS Physicians' beliefs about efficacy in subgroups of CD patients, safety, and patient preferences primarily motivate aminosalicylate prescription in CD. There is a lack of confidence in published clinical trials, and a desire for more robust evidence to inform 5-ASA use in CD.
Collapse
Affiliation(s)
- Christopher Ma
- Division of Gastroenterology and Hepatology, University of Calgary, Calgary, AB, Canada.,Robarts Clinical Trials, Inc., London, ON, Canada
| | - Carla Ascoytia
- Health Research Associates, Inc., Mountlake Terrace, WA, USA
| | | | - Mona Martin
- Health Research Associates, Inc., Mountlake Terrace, WA, USA
| | - Brian G Feagan
- Robarts Clinical Trials, Inc., London, ON, Canada.,Department of Medicine, Western University, London, ON, Canada.,Department of Biostatistics and Epidemiology, Western University, London, ON, Canada
| | - Vipul Jairath
- Robarts Clinical Trials, Inc., London, ON, Canada. .,Department of Medicine, Western University, London, ON, Canada. .,Department of Biostatistics and Epidemiology, Western University, London, ON, Canada.
| |
Collapse
|
|
46
|
Pathirana WPNGW, Chubb SAP, Gillett MJ, Vasikaran SD. Faecal Calprotectin. Clin Biochem Rev 2018; 39:77-90. [PMID: 30828114 PMCID: PMC6370282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/09/2023]
Abstract
Calprotectin is a calcium- and zinc-binding protein of the S-100 protein family which is mainly found within neutrophils and throughout the human body. The presence of calprotectin in faeces is a consequence of neutrophil migration into the gastrointestinal tissue due to an inflammatory process. Faecal calprotectin concentrations demonstrate good correlation with intestinal inflammation and faecal calprotectin is used as a biomarker in gastrointestinal disorders. Faecal calprotectin is a very sensitive marker for inflammation in the gastrointestinal tract, and useful for the differentiation of inflammatory bowel disease (IBD) from irritable bowel syndrome (IBS). Faecal calprotectin is used for the diagnosis, monitoring disease activity, treatment guidance and prediction of disease relapse and post-operative recurrence in IBD. There may also potentially be a role for faecal calprotectin in the management of infectious gastroenteritis, acute appendicitis, peptic ulcer disease, cystic fibrosis, coeliac disease, transplant rejection and graft versus host disease. Further studies are needed to confirm its utility in these conditions. Analysis of faecal calprotectin consists of an extraction step followed by quantification by immunoassay. Over the past few decades, several assays and extraction devices including point-of-care methods have been introduced by manufacturers. The manufacturer-quoted cut-off values for different faecal calprotectin assays are generally similar. However, the sensitivities and specificities at a given cut-off, and therefore the optimum cut-off values, are different between assays. A reference standard for calprotectin is lacking. Therefore, assay standardisation is required for more accurate and traceable test results for faecal calprotectin.
Collapse
Affiliation(s)
- WPN Ganga W Pathirana
- Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Fiona Stanley Hospital, Murdoch, WA 6150, Australia
| | - SA Paul Chubb
- Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Fiona Stanley Hospital, Murdoch, WA 6150, Australia
- School of Medicine, Faculty of Health and Medical Sciences, The University of Western Australia, Crawley, WA 6009, Australia
| | - Melissa J Gillett
- Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Fiona Stanley Hospital, Murdoch, WA 6150, Australia
| | - Samuel D Vasikaran
- Department of Clinical Biochemistry, PathWest Laboratory Medicine WA, Fiona Stanley Hospital, Murdoch, WA 6150, Australia
| |
Collapse
|
|
47
|
Zhu Z, Mei Z, Guo Y, Wang G, Wu T, Cui X, Huang Z, Zhu Y, Wen D, Song J, He H, Xu W, Cui L, Liu C. Reduced Risk of Inflammatory Bowel Disease-associated Colorectal Neoplasia with Use of Thiopurines: a Systematic Review and Meta-analysis. J Crohns Colitis 2018; 12:546-558. [PMID: 29370346 DOI: 10.1093/ecco-jcc/jjy006] [Citation(s) in RCA: 47] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2017] [Accepted: 01/15/2018] [Indexed: 12/18/2022]
Abstract
BACKGROUND AND AIMS The association between thiopurines and colorectal neoplasia risk remains controversial in inflammatory bowel disease [IBD] patients. We performed a systematic review and meta-analysis examining this association. METHODS A comprehensive search of the PubMed, EMBASE and Cochrane Library databases was performed to identify relevant literature. Random-effects models were applied to calculate the pooled odds ratio [OR] and relative risk [RR] with corresponding 95% confidence intervals [CIs] among case-control and cohort studies. RESULTS Eleven cohort and 16 case-control studies involving 95397 patients were included in this study. Overall, the use of thiopurines was associated with a reduced risk of colorectal neoplasia both in case-control [OR = 0.49, 95% CI: 0.34-0.70] and cohort studies [RR = 0.96, 95% CI: 0.94-0.98]. Moreover, a protective effect of thiopurines against advanced neoplasia [high-grade dysplasia and cancer] [OR = 0.51, 95% CI: 0.31-0.84 for case-control studies; RR = 0.96, 95% CI: 0.94-0.98 for cohort studies] and colorectal cancer [CRC] [OR = 0.56, 95% CI: 0.34-0.93 for case-control studies; RR = 0.96, 95% CI: 0.94-0.98 for cohort studies] was also observed. Furthermore, when the analysis was conducted on patients at a high risk for colorectal neoplasia, the chemopreventive effect was confirmed in patients with long disease duration [> 8 years] but not in those with extensive colitis or primary sclerosing cholangitis. CONCLUSIONS This study demonstrated that thiopurine use was associated with a reduced risk of colorectal neoplasia, advanced neoplasia and CRC in IBD patients, especially those with long disease duration [> 8 years].
Collapse
Affiliation(s)
- Zhehui Zhu
- Department of Colon and Rectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- Shanghai Colorectal Cancer Research Center, Shanghai, PR China
| | - Zubing Mei
- Department of Anorectal Surgery, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, PR China
| | - Yuegui Guo
- Department of Colon and Rectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- Shanghai Colorectal Cancer Research Center, Shanghai, PR China
| | - Guanghui Wang
- Department of Colon and Rectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- Shanghai Colorectal Cancer Research Center, Shanghai, PR China
| | - Tingyu Wu
- Department of Colon and Rectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- Shanghai Colorectal Cancer Research Center, Shanghai, PR China
| | - Ximao Cui
- Department of Colon and Rectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- Shanghai Colorectal Cancer Research Center, Shanghai, PR China
| | - Zhenyu Huang
- Shanghai Colorectal Cancer Research Center, Shanghai, PR China
| | - Yilian Zhu
- Department of Colon and Rectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- Shanghai Colorectal Cancer Research Center, Shanghai, PR China
| | - Dongpeng Wen
- Department of Colon and Rectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- Shanghai Colorectal Cancer Research Center, Shanghai, PR China
| | - Jinglve Song
- Department of Colon and Rectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- Shanghai Colorectal Cancer Research Center, Shanghai, PR China
| | - Hailan He
- Department of Colon and Rectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- Shanghai Colorectal Cancer Research Center, Shanghai, PR China
| | - Weimin Xu
- Department of Colon and Rectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- Shanghai Colorectal Cancer Research Center, Shanghai, PR China
| | - Long Cui
- Department of Colon and Rectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- Shanghai Colorectal Cancer Research Center, Shanghai, PR China
| | - Chenying Liu
- Department of Colon and Rectal Surgery, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China
- Shanghai Colorectal Cancer Research Center, Shanghai, PR China
| |
Collapse
|
|
48
|
Doherty G, Katsanos KH, Burisch J, Allez M, Papamichael K, Stallmach A, Mao R, Berset IP, Gisbert JP, Sebastian S, Kierkus J, Lopetuso L, Szymanska E, Louis E. European Crohn's and Colitis Organisation Topical Review on Treatment Withdrawal ['Exit Strategies'] in Inflammatory Bowel Disease. J Crohns Colitis 2018; 12:17-31. [PMID: 28981623 DOI: 10.1093/ecco-jcc/jjx101] [Citation(s) in RCA: 143] [Impact Index Per Article: 20.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2017] [Accepted: 07/31/2017] [Indexed: 12/12/2022]
Abstract
Clinically effective therapies now exist for remission maintenance in both ulcerative colitis [UC] and Crohn's Disease [CD]. For each major class of IBD medications [5-aminosalicyclates, immunomodulators, and biologic agents], used alone or in combination, there is a risk of relapse following reduction or cessation of treatment. A consensus expert panel convened by the European Crohn's and Colitis Organisation [ECCO] reviewed the published literature and agreed a series of consensus practice points. The objective of the expert consensus is to provide evidence-based guidance for clinical practice so that physicians can make informed decisions in partnership with their patients. The likelihood of relapse with stopping each class of IBD medication is reviewed. Factors associated with an altered risk of relapse with withdrawal are evaluated, and strategies to monitor and allow early identification of relapse are considered. In general, patients in clinical, biochemical, and endoscopic remission are more likely to remain well when treatments are stopped. Reintroduction of the same treatment is usually, but not always, successful. The decision to stop a treatment needs to be individualized, and shared decision making with the patient should take place.
Collapse
Affiliation(s)
- Glen Doherty
- Centre for Colorectal Disease, St Vincent's University Hospital & University College Dublin, Dublin, Ireland
| | - Konstantinos H Katsanos
- Department of Gastroenterology and Hepatology, University and Medical School of Ioannina, Ioannina, Greece
| | - Johan Burisch
- Department of Gastroenterology, North Zealand University Hospital, Frederikssund, Denmark
| | - Matthieu Allez
- Department of Gastroenterology and Hepatology, Hôpital Saint-Louis, APHP, INSERM UMRS 1160, Université Denis Diderot, Paris, France
| | | | - Andreas Stallmach
- Department of Internal Medicine IV [Gastroenterology, Hepatology and Infectious Disease], University Hospital Jena, Jena, Germany
| | - Ren Mao
- Department of Gastroenterology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China
| | - Ingrid Prytz Berset
- Gastroenterology Department, Alesund Hospital, Helse More Romsdal Hospital Trust, Alesund, Norway
| | - Javier P Gisbert
- Department of Gastroenterology, Hospital Universitario de la Princesa, Instituto de Investigaciun Sanitaria Princesa (IIS-IP) and Centro de Investigaciun Biomédica en Red de Enfermedades Heprticas y Digestivas (CIBEREHD), Madrid, Spain
| | - Shaji Sebastian
- IBD Unit, Department of Gastroenterology, Hull & East Yorkshire Hospitals NHS Trust, Hull, UK
| | - Jaroslaw Kierkus
- Department of Gastroenterology, Hepatology, Feeding Disorders and Pediatrics, Children's Memorial Health Institute, Warsaw, Poland
| | - Loris Lopetuso
- Department of Gastroenterology and Internal Medicine, Catholic University of Rome-A. Gemelli Hospital, Rome, Italy
| | - Edyta Szymanska
- Department of Pediatrics, Nutrition, and Metabolic Disorders, Children's Memorial Health Institute, Warsaw, Poland
| | - Edouard Louis
- Department of Gastroenterology, CHU Liège, Sart Tilman, Liège, Belgium
| |
Collapse
|
|
49
|
Flores BM, O'Connor A, Moss AC. Impact of mucosal inflammation on risk of colorectal neoplasia in patients with ulcerative colitis: a systematic review and meta-analysis. Gastrointest Endosc 2017; 86:1006-1011.e8. [PMID: 28750838 DOI: 10.1016/j.gie.2017.07.028] [Citation(s) in RCA: 73] [Impact Index Per Article: 9.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2017] [Accepted: 07/14/2017] [Indexed: 02/08/2023]
Abstract
BACKGROUND AND AIMS Long-standing ulcerative colitis is an established risk factor for colorectal neoplasia. A number of observational studies have suggested that evidence of mucosal inflammation (endoscopic or histologic) is associated with a greater risk for colorectal neoplasia than is mucosal healing. Our goal was to systematically analyze the risk of colorectal neoplasia in patients with ulcerative colitis who have ongoing mucosal inflammation to better inform surveillance strategies. METHODS We performed a systematic review and meta-analysis of the effect of endoscopic and/or histologic inflammation on the risk of colorectal neoplasia in cohort and case-control studies. Sensitivity analyses for study setting and case definition were performed. RESULTS Six studies met the inclusion criteria, incorporating outcomes in 1443 patients. No study used a single validated measure for mucosal inflammation. The pooled odds ratio for colorectal neoplasia was 3.5 (95% confidence interval [CI], 2.6-4.8; P < .001) in those with any mucosal inflammation and 2.6 (95% CI, 1.5-4.5; P = .01) in those with histologic inflammation, when compared with those with mucosal healing. The overall quality of the studies was good. CONCLUSION The presence of objective evidence of mucosal inflammation during follow-up in patients with ulcerative colitis is associated with a greater risk of subsequent colorectal neoplasia than in those with mucosal healing. This risk factor should be considered in guidelines on surveillance intervals for these patients.
Collapse
Affiliation(s)
- Brisas M Flores
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| | - Anthony O'Connor
- Leeds Gastroenterology Institute, St. James's University Hospital, Leeds, United Kingdom
| | - Alan C Moss
- Division of Gastroenterology, Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA
| |
Collapse
|
|
50
|
Namani A, Li J, Wang XJ, Tang X. A Review of Compounds for Prevention of Colorectal Cancer. ACTA ACUST UNITED AC 2017. [DOI: 10.1007/s40495-017-0101-6] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
|