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Gianfrancesco M, Awofeso A, Branquinho D, Guo X, McDonnell A, Jacobs W, Regueiro M. A narrative literature review of the incidence and prevalence of safety outcomes in patients with ulcerative colitis. Expert Rev Gastroenterol Hepatol 2025:1-18. [PMID: 40331585 DOI: 10.1080/17474124.2025.2501224] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/26/2024] [Revised: 04/06/2025] [Accepted: 04/29/2025] [Indexed: 05/08/2025]
Abstract
INTRODUCTION Information on rates of safety outcomes in patients with ulcerative colitis [UC] is helpful to better understand the benefit-risk profile of more recent therapies approved for UC. AREAS COVERED This narrative review provides an updated examination of the incidence and prevalence of safety outcomes in the UC patient population. Incidence and prevalence estimates were determined for outcomes including cardiac conduction disorders, infections, and malignancies from published literature [2013-2023]. EXPERT OPINION While information for certain outcomes was more frequently recorded, such as herpes viral infection (incidence rate [IR] 0.0-4.47 per 100 person-years [PY]) and malignancies [all; IR 0.0-1.77 per 100 PY], rarer outcome estimates such as bradycardia [IR 0.2 per 100 PY] and macular edema [IR 0.2 per 100 PY] were limited. Our knowledge of certain, uncommon safety outcomes and concomitant medical conditions in the UC population remains limited given the lack of data available. Even though larger cohorts with longer follow-up are warranted, estimates provided in this review will contribute to an improved understanding of the safety profile of UC therapies.
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Affiliation(s)
| | - Abiola Awofeso
- School of Community Health & Policy, Morgan State University, Baltimore, MD, USA
| | | | | | | | | | - Miguel Regueiro
- Department of Gastroenterology, Hepatology, and Nutrition, Cleveland Clinic, Cleveland, OH, USA
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Strigáč A, Caban M, Małecka-Wojciesko E, Talar-Wojnarowska R. Safety and Effectiveness of Thiopurines and Small Molecules in Elderly Patients with Inflammatory Bowel Diseases. J Clin Med 2024; 13:4678. [PMID: 39200823 PMCID: PMC11355586 DOI: 10.3390/jcm13164678] [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: 06/24/2024] [Revised: 08/02/2024] [Accepted: 08/05/2024] [Indexed: 09/02/2024] Open
Abstract
The management of inflammatory bowel diseases (IBD) requires weighing an individual patient's therapeutic benefits and therapy-related complication risks. The immunomodulators that have been commonly used so far in IBD therapy are thiopurines, including 6-mercaptopurine and azathioprine. As our understanding of the IBD pathomechanisms is widening, new therapeutic approaches are being introduced, including the Janus kinase (JAK) inhibitors and Sphingosine 1-phosphate receptor (S1PR) modulators' development. Non-selective JAK inhibitors are represented by tofacitinib, while selective JAK inhibitors comprise filgotinib and upadacitinib. As for the S1PR modulators, ozanimod and etrasimod are approved for UC therapy. The number of elderly patients with IBD is growing; therefore, this review aimed to evaluate the effectiveness and safety of the oral immunomodulators among the subjects aged ≥60. Possible complications limit the use of thiopurines in senior patients. Likewise, the promising effectiveness of new drugs in IBD therapy in those with additional risk factors might be confined by the risk of serious adverse events. However, the data regarding this issue are limited.
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Affiliation(s)
- Aleksandra Strigáč
- Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, 90-153 Lodz, Poland; (M.C.); (E.M.-W.); (R.T.-W.)
| | - Miłosz Caban
- Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, 90-153 Lodz, Poland; (M.C.); (E.M.-W.); (R.T.-W.)
- Department of Biochemistry, Faculty of Medicine, Medical University of Lodz, 92-215 Lodz, Poland
| | - Ewa Małecka-Wojciesko
- Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, 90-153 Lodz, Poland; (M.C.); (E.M.-W.); (R.T.-W.)
| | - Renata Talar-Wojnarowska
- Department of Digestive Tract Diseases, Faculty of Medicine, Medical University of Lodz, 90-153 Lodz, Poland; (M.C.); (E.M.-W.); (R.T.-W.)
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Viola A, Fiorino G, Costantino G, Fries W. Epidemiology and clinical course of late onset inflammatory bowel disease. Minerva Gastroenterol (Torino) 2024; 70:52-58. [PMID: 34057332 DOI: 10.23736/s2724-5985.21.02890-4] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
With the increasing age of the general population in developed countries, the management of several chronic diseases becomes more and more complex due to comorbidities. Some, especially inflammatory bowel diseases, formerly believed to belong to the young adult population, have now been recognized as being present at disease onset also in the ageing population, representing medical challenges different from those in the younger population. In the past few years, knowledge on this special older population has increased, changing initial beliefs concerning epidemiology and course of disease. In the present review, we addressed the most recent evidence concerning their current incidence compared with other age groups, their clinical course, potential risk factors for the development of late-onset IBDs, associated diseases, and cancer risk beyond therapy-related neoplasias.
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Affiliation(s)
- Anna Viola
- Gastroenterology and Clinical Unit for Chronic Bowel Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy -
| | - Gionata Fiorino
- Department of Gastroenterology, IBD Center, Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Giuseppe Costantino
- Gastroenterology and Clinical Unit for Chronic Bowel Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
| | - Walter Fries
- Gastroenterology and Clinical Unit for Chronic Bowel Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy
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Zamani M, Alizadeh-Tabari S. Does Elderly-Onset Inflammatory Bowel Disease Increase Risk of Colorectal Cancer? A Systematic Review and Meta-Analysis. J Clin Med 2023; 13:148. [PMID: 38202155 PMCID: PMC10779516 DOI: 10.3390/jcm13010148] [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: 11/08/2023] [Revised: 12/07/2023] [Accepted: 12/25/2023] [Indexed: 01/12/2024] Open
Abstract
BACKGROUND Although younger adults with inflammatory bowel disease (IBD) are known to have an increased risk of developing colorectal cancer (CRC), the impact of IBD on CRC risk in elderly patients is not yet fully understood. Therefore, we conducted this systematic review and meta-analysis to address this knowledge gap. METHODS We thoroughly searched Embase, PubMed, and Scopus, covering the literature from inception to 31 August 2023, in any language. We enrolled population-based cohort studies that appraised the risk of CRC development in elderly patients (≥60 years) with IBD as compared to the non-IBD population. Our meta-analysis provided pooled relative risk (RR) with 95% confidence intervals (CIs) using a random-effect model. RESULTS Out of 3904 citations, 3 eligible cohort studies were ultimately included, reporting 694 CRC events in 35,187 patients with IBD. According to analysis, the risk of developing CRC did not increase in patients with elderly-onset IBD (RR = 1.17 [95% CI: 0.86-1.47]; I2 = 62.6%). This lack of a significant association was observed in both patients with Crohn's disease (RR = 1.28 [95% CI: 0.88-1.69]) and ulcerative colitis (RR = 0.99 [95% CI: 0.90-1.09]) (p for interaction = 0.166). CONCLUSION Our findings revealed no significant increase in the risk of incident CRC in patients with elderly-onset IBD, suggesting that intense screening of these patients for CRC may not be necessary.
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Affiliation(s)
- Mohammad Zamani
- Digestive Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran 1411713135, Iran
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Dan WY, Zhou GZ, Peng LH, Pan F. Update and latest advances in mechanisms and management of colitis-associated colorectal cancer. World J Gastrointest Oncol 2023; 15:1317-1331. [PMID: 37663937 PMCID: PMC10473934 DOI: 10.4251/wjgo.v15.i8.1317] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/30/2023] [Revised: 07/03/2023] [Accepted: 07/25/2023] [Indexed: 08/10/2023] Open
Abstract
Colitis-associated colorectal cancer (CAC) is defined as a specific cluster of colorectal cancers that develop as a result of prolonged colitis in patients with inflammatory bowel disease (IBD). Patients with IBD, including ulcerative colitis and Crohn's disease, are known to have an increased risk of developing CAC. Although the incidence of CAC has significantly decreased over the past few decades, individuals with CAC have increased mortality compared to individuals with sporadic colorectal cancer, and the incidence of CAC increases with duration. Chronic inflammation is generally recognized as a major contributor to the pathogenesis of CAC. CAC has been shown to progress from colitis to dysplasia and finally to carcinoma. Accumulating evidence suggests that multiple immune-mediated pathways, DNA damage pathways, and pathogens are involved in the pathogenesis of CAC. Over the past decade, there has been an increasing effort to develop clinical approaches that could help improve outcomes for CAC patients. Colonoscopic surveillance plays an important role in reducing the risk of advanced and interval cancers. It is generally recommended that CAC patients undergo endoscopic removal or colectomy. This review summarizes the current understanding of CAC, particularly its epidemiology, mechanisms, and management. It focuses on the mechanisms that contribute to the development of CAC, covering advances in genomics, immunology, and the microbiome; presents evidence for management strategies, including endoscopy and colectomy; and discusses new strategies to interfere with the process and development of CAC. These scientific findings will pave the way for the management of CAC in the near future.
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Affiliation(s)
- Wan-Yue Dan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- Medical School, Nankai University, Tianjin 300071, China
| | - Guan-Zhou Zhou
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
- Medical School, Nankai University, Tianjin 300071, China
| | - Li-Hua Peng
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
| | - Fei Pan
- Department of Gastroenterology and Hepatology, The First Medical Center, Chinese PLA General Hospital, Beijing 100853, China
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Sousa P, Bertani L, Rodrigues C. Management of inflammatory bowel disease in the elderly: A review. Dig Liver Dis 2023; 55:1001-1009. [PMID: 36681569 DOI: 10.1016/j.dld.2022.12.024] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/19/2022] [Revised: 12/26/2022] [Accepted: 12/29/2022] [Indexed: 01/23/2023]
Abstract
The burden of Inflammatory Bowel Disease (IBD) is increasing worldwide, with a particular increase in the prevalence in the elderly population, due to the ageing of young-onset IBD as well as to the increasing incidence in elderly patients. Elderly IBD patients present specific challenges to the treating physician, as they have comorbidities, lower functional reserves, and higher risk of treatment-related complications. The diagnosis of IBD in the elderly may be difficult due to a more subtle disease presentation and to a wide range of differential diagnosis. Moreover, as these patients are often excluded from clinical trials, there is a lack of high-quality evidence to inform on the most appropriate management. Despite an increasing prevalence, the management of IBD in the elderly is still hindered by frequent misconceptions by physicians treating these patients. Due to a erroneous notion of a milder disease course and fear of adverse events, elderly IBD-patients are managed with frequent and continuous use of steroids and undertreated with effective medical therapies. In this review, we describe the principles of management of IBD in the elderly, which is a topic of increasing importance to IBD clinics, that will have to progressively adapt to care for an ageing population.
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Affiliation(s)
- Paula Sousa
- Department of Gastroenterology, Viseu Unit, Tondela-Viseu Hospital Centre, Viseu 3504-509, Portugal.
| | - Lorenzo Bertani
- Department of General Surgery and Gastroenterology, Tuscany North West ASL, Pontedera Hospital, Pontedera, Italy
| | - Cláudio Rodrigues
- Department of Gastroenterology, Viseu Unit, Tondela-Viseu Hospital Centre, Viseu 3504-509, Portugal
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Massano A, Bertin L, Zingone F, Buda A, Visaggi P, Bertani L, de Bortoli N, Fassan M, Scarpa M, Ruffolo C, Angriman I, Bezzio C, Casini V, Ribaldone DG, Savarino EV, Barberio B. Extraintestinal Cancers in Inflammatory Bowel Disease: A Literature Review. Cancers (Basel) 2023; 15:3824. [PMID: 37568640 PMCID: PMC10417189 DOI: 10.3390/cancers15153824] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 07/24/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a group of chronic multifactorial inflammatory disorders including two major entities: Crohn's disease (CD) and ulcerative colitis (UC). Preliminary evidence suggests that patients with IBD may be at increased risk of developing intestinal and extraintestinal cancers (EICs). Actually, little is known about the association between IBD and EICs, and there is ever-growing concern regarding the safety of immunomodulators and biological therapy, which may represent a risk factor for carcinogenesis. AIMS The aim of this review is to summarize the evidence regarding the association between IBD and EICs, the safety of immunomodulators and biological therapy and the management of immunomodulators and biologic agents in IBD patients with prior or current EICs. RESULTS IBD patients have a higher risk of developing different forms of extraintestinal solid organ tumors and hematological malignancies. Immunomodulators and biological therapy may increase the risk of developing some types of EICs and may be consciously used in patients with IBD and current or prior history of malignancy. CONCLUSIONS Decisions regarding the use of immunomodulators or biological therapies should be made on an individual basis, considering a multidisciplinary approach involving oncologists.
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Affiliation(s)
- Alessandro Massano
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Luisa Bertin
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Fabiana Zingone
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Andrea Buda
- Gastroenterology Unit, Department of Gastrointestinal Oncological Surgery, S. Maria del Prato Hospital, 32032 Feltre, Italy;
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (P.V.); (L.B.); (N.d.B.)
| | - Lorenzo Bertani
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (P.V.); (L.B.); (N.d.B.)
| | - Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (P.V.); (L.B.); (N.d.B.)
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine, University of Padova, 35138 Padova, Italy;
| | - Marco Scarpa
- General Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padova, Italy; (M.S.); (C.R.); (I.A.)
| | - Cesare Ruffolo
- General Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padova, Italy; (M.S.); (C.R.); (I.A.)
| | - Imerio Angriman
- General Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padova, Italy; (M.S.); (C.R.); (I.A.)
| | - Cristina Bezzio
- IBD Center, Gastroenterology Unit, Rho Hospital, ASST Rhodense, 20017 Rho, Italy;
| | | | - Davide Giuseppe Ribaldone
- Department of Medical Sciences, Division of Gastroenterology, University of Turin, 10126 Turin, Italy;
| | - Edoardo Vincenzo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
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Tulewicz-Marti E, Stępień-Wrochna B, Maciejewska K, Łodyga M, Karłowicz K, Lewandowski K, Rydzewska G. Awareness and Compliance with the Recommendations of Primary and Secondary Prevention of Cancer in Patients with Inflammatory Bowel Disease. J Pers Med 2023; 13:913. [PMID: 37373902 DOI: 10.3390/jpm13060913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 05/23/2023] [Accepted: 05/27/2023] [Indexed: 06/29/2023] Open
Abstract
INTRODUCTION Patients with Inflammatory Bowel Disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are at high risk of developing malignancies, so prevention and adherence to cancer screening may improve detection. The aim of this study was to assess compliance with medical recommendations, especially primary and secondary prevention of cancer. METHODS This one-center cross-sectional study was carried out between June and December 2021 amongst patients at the Department of Internal Medicine and Gastroenterology, IBD Division, National Medical Institute of Ministry of Interior Affairs and Administrations, or the outpatient clinic. Patients with IBD were asked to complete an anonymous questionnaire, which included 42 questions concerning lifestyle, cancer risk factors, cancer history, and checkups. STATISTICAL METHODS The results of the qualitative variables were expressed as frequencies and percentages. We used Fisher's exact test and the Chi-squared test. A value of p < 0.05 was considered significant. Statistical analyses were performed with the SPSS statistical package. RESULTS A total of 313 patients were enrolled in the study: 145 women and 168 men. In the group, 182 had Crohn's disease (CD), 120 had ulcerative colitis (UC), and 11 with IBDU (unclassified IBD). Most participants had a disease duration of over 8 years and received biological treatment, corticoids, and/or immunosuppressive therapy. Amongst respondents, 17% (31) of patients with CD and 25.8% (31) with UC were overweight, and 10.5% (19) with CD and 15.8% (19) with UC were obese (p = 0.017). We found that 16.3% of all respondents were smokers (79.6% (144) with CD, 90.8% (109) with UC, and 72.7% (8) with IBDU; p = 0.053), and 33.9% declared that they consumed alcohol (39.4% (71) with CD, 26.9% (32) with UC, and 18.2% (2) with IBDU; p = 0.045). A total of 25.4% of patients were exposed to UV radiation, but only 18.8% used sunblock. In addition, 58.8% (67) of patients with CD and 35.8% (19) with UC receiving immunosuppressants had regular laboratory tests (p = 0.02). Furthermore, 41.4% (46) of patients with UC, 27.1% (49) of patients with CD, and 70.0% (7) of patients with IBDU declared not to perform any dermatological control (p = 0.013). A total of 77% of patients had abdominal ultrasound. Out of 52.9% of patients for whom colonoscopy was recommended, only 27.3% had it performed (16.9% (30) with CD vs. 43.1% (50) with UC p < 0.001). Most examinations were ordered by gastroenterologists. Female patients had regular breast control (CD, 78.6% (66); UC, 91.2% (52); IBDU, 50% (2); p = 0.034), and 93.8% (76) had gynecological examinations. Additionally, 80.2% of patients knew about HPV, but most declared not to be vaccinated. A total of 17.9% of patients had urological control, but most had no important pathology detected. CONCLUSIONS According to our study, many patients are still exposed to risk factors, such as obesity, smoking, and low physical activity, that are modifiable. Laboratory tests in patients with immunosuppressive treatment should be performed regularly. Systematic control, especially dermatological checkups, should be recommended. Additionally, not only gastrologists but also other specialists and GPs should remind patients about regular checkups. Primary prevention, such as HPV vaccinations, should be recommended to all patients.
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Affiliation(s)
- Edyta Tulewicz-Marti
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Unit, National Medical Institute of the Ministry of Interior Affairs and Administration-Warsaw, 02-507 Warsaw, Poland
| | - Beata Stępień-Wrochna
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Unit, National Medical Institute of the Ministry of Interior Affairs and Administration-Warsaw, 02-507 Warsaw, Poland
| | - Katarzyna Maciejewska
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Unit, National Medical Institute of the Ministry of Interior Affairs and Administration-Warsaw, 02-507 Warsaw, Poland
| | - Michał Łodyga
- Internal Medicine Department, Grochowski Hospital, 04-073 Warsaw, Poland
- Department of Internal Medicine, Faculty of Health Science, Medical University of Warsaw, 02-091 Warszawa, Poland
| | - Katarzyna Karłowicz
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Unit, National Medical Institute of the Ministry of Interior Affairs and Administration-Warsaw, 02-507 Warsaw, Poland
| | - Konrad Lewandowski
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Unit, National Medical Institute of the Ministry of Interior Affairs and Administration-Warsaw, 02-507 Warsaw, Poland
| | - Grazyna Rydzewska
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Unit, National Medical Institute of the Ministry of Interior Affairs and Administration-Warsaw, 02-507 Warsaw, Poland
- Collegium Medicum, Jana Kochanowski University, 25-317 Kielce, Poland
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Surveillance for Colorectal Neoplasia in Inflammatory Bowel Disease: When to Stop. Am J Gastroenterol 2023; 118:429-431. [PMID: 36584365 DOI: 10.14309/ajg.0000000000002168] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/25/2022] [Accepted: 12/21/2022] [Indexed: 01/01/2023]
Abstract
Patients with chronic ulcerative and Crohn's colitis are at increased risk for colorectal neoplasia(CRN [dysplasia and cancer]) compared to the general population. Risk factors for CRN include extent of colitis, cumulative inflammatory burden, family history of colorectal cancer, and primary sclerosing cholangitis. Best practices to prevent CRN include control of colonic inflammation, high quality surveillance colonoscopy with or without enhanced imaging techniques, resection of visible dysplasia if possible, and colectomy in patients with unresectable dysplasia, invisible multifocal low grade dysplasia, or invisible high grade dysplasia. Cessation of dysplasia surveillance is individualized and should involve shared decision making based on factors including but not limited to chronologic age, frailty, co-morbid conditions, life expectancy, results of prior surveillance exams, and risk factors for CRN.
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Wu S, Xie S, Yuan C, Yang Z, Liu S, Zhang Q, Sun F, Wu J, Zhan S, Zhu S, Zhang S. Inflammatory Bowel Disease and Long-term Risk of Cancer: A Prospective Cohort Study Among Half a Million Adults in UK Biobank. Inflamm Bowel Dis 2023; 29:384-395. [PMID: 35639937 DOI: 10.1093/ibd/izac096] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/14/2022] [Indexed: 12/09/2022]
Abstract
BACKGROUND This study aims to examine the prospective association of inflammatory bowel disease (IBD) with long-term risk of overall, site-specific cancer and cancer-specific mortality in middle-aged and older people. METHODS The study included participants free of any cancer at baseline from the UK Biobank, with IBD patients as an exposure group and non-IBD patients as a reference group. Primary outcome was the incidence of overall cancer and cancer-specific mortality. Secondary outcomes included site-specific cancers and types of digestive cancers. Cox proportional hazard model was used to investigate the associated risk of incident malignancies and related mortality. RESULTS Among 455 927 participants, 5142 were diagnosed with IBD (3258 ulcerative colitis [UC]; 1449 Crohn's disease [CD]; others unspecified). During a median of 12.2-year follow-up, 890 cases of incident cancer were identified in IBD patients (15.74 per 1000 person years) compared with 63 675 cases in reference individuals (12.46 per 1000 person years). Of these cases, 220 and 12 838 cancer-specific deaths occurred in IBD and non-IBD groups. Compared with non-IBD participants, the adjusted hazard ratio (AHR) for overall cancer and cancer-specific mortality was 1.17 (95% CI, 1.09-1.25) and 1.26 (95% CI, 1.18-1.35) among IBD patients, with an AHR of 1.15 (95% CI, 1.02-1.31) and 1.38 (95% CI, 1.08-1.75) in UC and 1.15 (95% CI, 1.06-1.25) and 1.25 (95% CI, 1.06-1.49) in CD, respectively. Specifically, increased risk of digestive (1.33; 95% CI, 1.12-1.57), nonmelanoma (1.25; 95% CI, 1.11-1.41), and male genital (1.29; 95% CI, 1.09-1.52) cancers was observed in IBD patients. CONCLUSIONS Compared with non-IBD, IBD may be associated with an increased risk of overall cancer and cancer-specific mortality, particularly digestive cancers, nonmelanoma and male genital cancers.
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Affiliation(s)
- Shanshan Wu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
| | - Sian Xie
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
| | - Changzheng Yuan
- School of Public Health, Zhejiang University School of Medicine, Hangzhou 310058, Zhejiang, China
- Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA
| | - Zhirong Yang
- Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, China
- Primary Care Unit, Department of Public Health and Primary Care, School of Clinical Medicine, University of Cambridge, Cambridge, CB18RN, UK
| | - Si Liu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
| | - Qian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
| | - Feng Sun
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, 100191, China
| | - Jing Wu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
| | - Siyan Zhan
- Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, 100191, China
| | - Shengtao Zhu
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
| | - Shutian Zhang
- Department of Gastroenterology, Beijing Friendship Hospital, Capital Medical University, National Clinical Research Center for Digestive Disease, Beijing Digestive Disease Center, Beijing Key Laboratory for Precancerous Lesion of Digestive Disease, Beijing, 100050, China
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Therapeutic Management of Adults with Inflammatory Bowel Disease and Malignancies: A Clinical Challenge. Cancers (Basel) 2023; 15:cancers15020542. [PMID: 36672491 PMCID: PMC9856548 DOI: 10.3390/cancers15020542] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/13/2022] [Revised: 01/11/2023] [Accepted: 01/14/2023] [Indexed: 01/19/2023] Open
Abstract
Patients with chronic inflammatory bowel diseases (IBD) have increased risk of developing intestinal and extraintestinal cancers. However, once a diagnosis of malignancy is made, the therapeutic management of Crohn's disease (CD) and ulcerative colitis (UC) can be challenging as major guidelines suggest discontinuing the ongoing immunosuppressant and biological therapies for at least 2-5 years after the end of cancer treatment. Recently, new molecules such as vedolizumab and ustekinumab have been approved for IBD and limited data exist on the real risk of new or recurrent cancer in IBD patients with prior cancer, exposed to immunosuppressants and biologic agents. Thus, a multidisciplinary approach and case-by-case management is the preferred choice. The primary aim of our review was to summarize the current evidence about the safety of reintroducing an immunosuppressant or biologic agent in patients with a history of malignancy and to compare the different available therapies, including gut-selective agents. The secondary aim was to evaluate the clinical course of the IBD patients under cancer treatment who do not receive any specific immunosuppressant treatment after the diagnosis of cancer.
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12
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Alehashemi S, Ward MM. Risk of Hematologic Malignancies in Elderly Patients With Ankylosing Spondylitis: A Cohort Study and Systematic Review. Mayo Clin Proc 2023; 98:100-110. [PMID: 36470752 PMCID: PMC9822846 DOI: 10.1016/j.mayocp.2022.06.030] [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: 08/20/2021] [Revised: 05/09/2022] [Accepted: 06/30/2022] [Indexed: 12/04/2022]
Abstract
OBJECTIVE To examine the risk of hematologic malignancies in older adults with ankylosing spondylitis (AS). PATIENTS AND METHODS We used US Medicare data from January 1, 1999, to December 31, 2010, to identify a population-based cohort of beneficiaries with AS. We also included beneficiaries with inflammatory bowel disease (IBD) as disease controls and beneficiaries without AS or IBD as unaffected controls. We excluded those treated with tumor necrosis factor inhibitors in this period. We followed up each group for new diagnosis claims for hematologic malignancies until September 30, 2015. RESULTS We included 12,451 beneficiaries with AS, 234,905 with IBD, and 10,975,340 unaffected controls, with a mean follow-up of 9.9, 9.3, and 8.0 years, respectively. We identified 297 hematologic malignancies in the AS group, 4538 malignancies in the IBD group, and 128,239 malignancies in unaffected controls. The standardized incidence ratio in AS vs unaffected controls was 1.39 (95% CI, 1.05 to 1.61) for non-Hodgkin lymphoma, 1.50 (95% CI, 1.17 to 1.92) for chronic lymphocytic leukemia, and 1.52 (95% CI, 1.12 to 2.06) for multiple myeloma. Risks of acute myeloid leukemia and chronic myeloid leukemia were not elevated in AS, and there were too few cases of Hodgkin lymphoma to compute risks. Risks were comparable to those of beneficiaries with IBD. We also performed a systematic literature review of the risk of hematologic malignancy in AS, focusing on age associations, which have not been previously examined. We identified 21 studies in the systematic literature review, which included mainly young or middle-aged patients. Results suggested that AS was largely not associated with an increased risk of hematologic malignancies. Two cohort studies reported an increased risk of multiple myeloma in AS. CONCLUSION The risks of non-Hodgkin lymphoma, chronic lymphocytic leukemia, and multiple myeloma are increased among elderly patients with AS.
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MESH Headings
- Middle Aged
- Humans
- Aged
- United States/epidemiology
- Multiple Myeloma/complications
- Cohort Studies
- Leukemia, Lymphocytic, Chronic, B-Cell/epidemiology
- Leukemia, Lymphocytic, Chronic, B-Cell/complications
- Spondylitis, Ankylosing/complications
- Spondylitis, Ankylosing/drug therapy
- Spondylitis, Ankylosing/epidemiology
- Medicare
- Hematologic Neoplasms/complications
- Lymphoma, Non-Hodgkin/epidemiology
- Lymphoma, Non-Hodgkin/etiology
- Lymphoma, Non-Hodgkin/pathology
- Inflammatory Bowel Diseases/complications
- Inflammatory Bowel Diseases/drug therapy
- Inflammatory Bowel Diseases/epidemiology
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Affiliation(s)
- Sara Alehashemi
- National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD.
| | - Michael M Ward
- Intramural Research Program, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD
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13
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Weiss A, Buchner AM. Editorial: colorectal cancer in elderly-onset inflammatory bowel disease-what is the risk? Aliment Pharmacol Ther 2022; 56:1421-1422. [PMID: 36221162 DOI: 10.1111/apt.17207] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
LINKED CONTENTThis article is linked to Everhov et al papers. To view these articles, visit https://doi.org/10.1111/apt.17175 and https://doi.org/10.1111/apt.17229
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Affiliation(s)
- Alexandra Weiss
- Department of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
| | - Anna M Buchner
- Department of Gastroenterology and Hepatology, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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14
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Li Y, Chen QQ, Zhu WY, Deng F, Li DW, Li J, Wan J, Ling Hu EQ. Mesenchymal stem cell transplantation worsens intestinal inflammation and microenvironment in PI3Kγ-knockout mice. Cell Immunol 2022; 380:104573. [PMID: 36031460 DOI: 10.1016/j.cellimm.2022.104573] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/18/2022] [Revised: 06/15/2022] [Accepted: 06/19/2022] [Indexed: 11/03/2022]
Abstract
Considering the possible interaction between mesenchymal stem cells (MSCs) and PI3Kγ-associated drugs, we evaluated the efficacy and action mechanism of MSCs in the treatment of colitis in PI3Kγ-/- mice. Trinitro-benzene-sulfonic acid enema was used to create a colitis model, and MSCs were transplanted through the caudal vein to treat colitis in wild-type and PI3Kγ-/- mice. We sequenced microbial 16S rRNA genes in the colonic mucosa of PI3Kγ-/- and wild-type mice and quantified colonic IgA, IL-2, IL-10, IL-17A, occludin, and serum IgA. MSC transplantation led to a more serious reduction in the weight of trinitro-benzene-sulfonic acid-administered PI3Kγ-/- mice than that in wild-type mice. The disease activity index, pathological scoring, number of taxa in the colon, Berger-Parker index, I-index, proportion of Proteobacteria, and IgA level in the blood were higher in PI3Kγ-/- mice than in wild-type mice after MSC transplantation. The occludin and IL-10 levels in the colon tissues decreased before and after MSC transplantation in PI3Kγ-/- mice, whereas they were increased in wild-type mice The IL-17 level decreased in both wild-type and PI3Kγ-/- mice, with knockout mice showing a greater decrease. Therefore, MSC transplantation in PI3Kγ-/- mice led to increased numbers of exogenous pathogenic microorganisms and enhanced colitis that was difficult to relieve.
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Affiliation(s)
- Yi Li
- Department of Gastroenterology, the First Medical Center, General Hospital of the Chinese People's Liberation Army, No. 28, Fu Xing Road, Hai Dian District, Beijing 100853, China.
| | - Qian-Qian Chen
- Department of Gastroenterology, the First Medical Center, General Hospital of the Chinese People's Liberation Army, No. 28, Fu Xing Road, Hai Dian District, Beijing 100853, China.
| | - Wen-Ya Zhu
- Department of Gastroenterology, the Sixth Medical Center, General Hospital of the Chinese People's Liberation Army, No. 6, Fu Cheng Road, Hai Dian District, Beijing 100048, China.
| | - Fen Deng
- Department of Gastroenterology, the First Medical Center, General Hospital of the Chinese People's Liberation Army, No. 28, Fu Xing Road, Hai Dian District, Beijing 100853, China.
| | - Da-Wei Li
- Department of Gastroenterology, the Sixth Medical Center, General Hospital of the Chinese People's Liberation Army, No. 6, Fu Cheng Road, Hai Dian District, Beijing 100048, China.
| | - Jia Li
- Department of Gastroenterology, the Second Medical Center, General Hospital of the Chinese People's Liberation Army, No. 28, Fu Xing Road, Hai Dian District, Beijing 100853, China.
| | - Jun Wan
- Department of Gastroenterology, the Second Medical Center, General Hospital of the Chinese People's Liberation Army, No. 28, Fu Xing Road, Hai Dian District, Beijing 100853, China.
| | - En-Qiang Ling Hu
- Department of Gastroenterology, the First Medical Center, General Hospital of the Chinese People's Liberation Army, No. 28, Fu Xing Road, Hai Dian District, Beijing 100853, China.
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15
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Everhov ÅH, Erichsen R, Järås J, Pedersen L, Halfvarson J, Askling J, Ekbom A, Ludvigsson JF, Toft Sørensen H, Olén O. Colorectal cancer in elderly-onset inflammatory bowel disease: a 1969-2017 Scandinavian register-based cohort study. Aliment Pharmacol Ther 2022; 56:1168-1182. [PMID: 35916190 PMCID: PMC9545052 DOI: 10.1111/apt.17175] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 04/10/2022] [Accepted: 07/23/2022] [Indexed: 01/30/2023]
Abstract
BACKGROUND Previous research indicates that the increased relative risk of colorectal cancer (CRC) in inflammatory bowel disease (IBD) is limited to young-onset IBD. AIM To estimate risks of incident CRC and death from CRC in elderly-onset IBD METHODS: Patients diagnosed with IBD at age ≥ 60 years between 1969 and 2017 were identified using Danish and Swedish National Patient Registers and histopathology data. We linked data to Cancer and Causes of Death Registers and used Cox regression to estimate hazard ratios (HRs) for CRC diagnosis and death compared to matched (by sex, age, and region) IBD-free individuals. RESULTS Among 7869 patients with Crohn's disease followed for 54,220 person-years, and 21,224 patients with ulcerative colitis (UC) followed for 142,635 person-years, 2.10% and 1.90% were diagnosed with CRC, compared to 2.26% and 2.34% of reference individuals (median follow-up 6 and 7 years). The incidence of CRC was elevated during the first year after IBD diagnosis: 4.36 (95% CI = 3.33-5.71) in Crohn's disease and 2.48 (95% CI = 2.03-3.02) in UC, but decreased after the first year of follow-up: 0.69 (95% CI = 0.56-0.86) and 0.78 (95% CI = 0.69-0.88). Once diagnosed with CRC, the risk of CRC death was similar for IBD patients and the general population. CONCLUSION The excess risk of CRC in elderly-onset IBD was probably due to bias and not observed beyond the first year. From 2010, the HR for CRC diagnosis more than 1 year after initial IBD diagnosis was lower than in the largely unscreened reference population, supporting the benefit of endoscopic screening and surveillance in patients with IBD.
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Affiliation(s)
- Åsa H. Everhov
- Department of Clinical Science and Education SödersjukhusetKarolinska InstitutetStockholmSweden
- Clinical Epidemiology Division, Department of MedicineSolna Karolinska InstitutetStockholmSweden
| | - Rune Erichsen
- Department of Clinical EpidemiologyAarhus University Hospital and Aarhus UniversityAarhusDenmark
- Department of SurgeryRanders Regional HospitalRandersDenmark
| | - Jacob Järås
- Clinical Epidemiology Division, Department of MedicineSolna Karolinska InstitutetStockholmSweden
| | - Lars Pedersen
- Department of Clinical EpidemiologyAarhus University Hospital and Aarhus UniversityAarhusDenmark
| | - Jonas Halfvarson
- Department of Gastroenterology, Faculty of Medicine and HealthÖrebro UniversityÖrebroSweden
| | - Johan Askling
- Clinical Epidemiology Division, Department of MedicineSolna Karolinska InstitutetStockholmSweden
| | - Anders Ekbom
- Clinical Epidemiology Division, Department of MedicineSolna Karolinska InstitutetStockholmSweden
| | - Jonas F. Ludvigsson
- Department of Medical Epidemiology and BiostatisticsKarolinska InstitutetStockholmSweden
- Department of PediatricsOrebro University HospitalOrebroSweden
- Division of Epidemiology and Public Health, School of MedicineUniversity of NottinghamNottinghamUK
- Department of MedicineColumbia University College of Physicians and SurgeonsNew York CityNew YorkUSA
| | - Henrik Toft Sørensen
- Department of Clinical EpidemiologyAarhus University Hospital and Aarhus UniversityAarhusDenmark
| | - Ola Olén
- Department of Clinical Science and Education SödersjukhusetKarolinska InstitutetStockholmSweden
- Clinical Epidemiology Division, Department of MedicineSolna Karolinska InstitutetStockholmSweden
- Sachs' Children and Youth HospitalStockholm South General HospitalStockholmSweden
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16
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Nguyen TB, Do DN, Nguyen-Thi ML, Hoang-The H, Tran TT, Nguyen-Thanh T. Identification of potential crucial genes and key pathways shared in Inflammatory Bowel Disease and cervical cancer by machine learning and integrated bioinformatics. Comput Biol Med 2022; 149:105996. [DOI: 10.1016/j.compbiomed.2022.105996] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/08/2022] [Revised: 07/10/2022] [Accepted: 08/14/2022] [Indexed: 11/15/2022]
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17
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Piovani D, Hassan C, Repici A, Rimassa L, Carlo-Stella C, Nikolopoulos GK, Riboli E, Bonovas S. Risk of Cancer in Inflammatory Bowel Diseases: Umbrella Review and Reanalysis of Meta-analyses. Gastroenterology 2022; 163:671-684. [PMID: 35643170 DOI: 10.1053/j.gastro.2022.05.038] [Citation(s) in RCA: 31] [Impact Index Per Article: 10.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2022] [Revised: 05/16/2022] [Accepted: 05/18/2022] [Indexed: 12/11/2022]
Abstract
BACKGROUND & AIMS To summarize the epidemiologic evidence and assess the validity of claimed associations of inflammatory bowel diseases (IBDs) with overall and site-specific cancer risk. METHODS We systematically searched PubMed, Embase, and Scopus from inception to May 10, 2021, to identify and comprehensively reanalyze the data of meta-analyses on associations between IBDs (ie, Crohn's disease [CD] and ulcerative colitis [UC]) and subsequent risk of cancer. The strength of epidemiologic evidence was graded as high, moderate, or weak, by applying prespecified criteria that included the random effects estimate, its 95% confidence interval, and P value, estimates of heterogeneity, small-study effects, and robustness to unmeasured confounding. RESULTS This study critically appraised 277 estimates derived from 24 published meta-analyses and our own meta-analyses. The association between pediatric-onset IBDs and overall risk of cancer showed high epidemiologic evidence. Twenty associations (15 cancer types) demonstrated moderate evidence: any cancer (pediatric-onset UC), mouth to terminal ileum (CD), small bowel (CD/UC), colon (CD), rectum (CD/UC), colon-rectum (IBDs, pediatric-onset CD/UC), bile ducts and liver (CD/UC), liver (CD), intrahepatic cholangiocarcinoma (IBDs), bile ducts (CD), skin (CD), squamous cell carcinoma of the skin (CD), nonmelanoma skin cancer (UC), kidney (CD), and thyroid cancer (IBDs). Another 40 associations (23 cancer types) showed statistical significance; however, our confidence in these effect estimates was weak. No statistical significance was found regarding further 47 associations. CONCLUSIONS Associations between IBDs and different types of malignancy showed varying levels of evidence and magnitude of risk. Further primary research investigating the impact of a consistent set of risk factors that are known to affect cancer risk is warranted. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42021254996.
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Affiliation(s)
- Daniele Piovani
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Cesare Hassan
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Alessandro Repici
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Lorenza Rimassa
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Carmelo Carlo-Stella
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; Humanitas Cancer Center, IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy
| | - Georgios K Nikolopoulos
- Laboratory of Medical Statistics, Epidemiology and Public Health, Medical School, University of Cyprus, Nicosia, Cyprus
| | - Elio Riboli
- Department of Epidemiology and Biostatistics, School of Public Health, Imperial College London, London, United Kingdom
| | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Milan, Italy; IRCCS Humanitas Research Hospital, Rozzano, Milan, Italy.
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18
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Abstract
Inflammatory bowel diseases (IBD), including Crohn disease and ulcerative colitis, are chronic inflammatory conditions of the gastrointestinal tract. Individuals with IBD are at increased risk for several malignancies originating in the intestine, such as colorectal cancer, small bowel adenocarcinoma, intestinal lymphoma, and anal cancer. There are also several extraintestinal malignancies associated with IBD and IBD therapies, including cholangiocarcinoma, skin cancer, hematologic malignancies, genitourinary cancer, cervical cancer, and prostate cancer. The authors summarize the risk of cancer in patients with IBD, diagnosis and management of colorectal neoplasia in IBD, and management of patients with IBD and active or recent cancer.
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Affiliation(s)
- Adam S Faye
- Inflammatory Bowel Disease Center at NYU Langone Health, 305 East 33rd Street, Lower Level, New York, NY 10016, USA
| | - Ariela K Holmer
- Inflammatory Bowel Disease Center at NYU Langone Health, 305 East 33rd Street, Lower Level, New York, NY 10016, USA
| | - Jordan E Axelrad
- Inflammatory Bowel Disease Center at NYU Langone Health, 305 East 33rd Street, Lower Level, New York, NY 10016, USA.
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19
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Minnis-Lyons SE, Aiken Z, Chow S, Din S. Managing IBD in patients with previous cancers. Frontline Gastroenterol 2022; 13:e44-e50. [PMID: 35812021 PMCID: PMC9234723 DOI: 10.1136/flgastro-2022-102187] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/04/2022] [Accepted: 05/15/2022] [Indexed: 02/04/2023] Open
Abstract
A frequent dilemma faced in the inflammatory bowel disease (IBD) clinic is how to best treat a patient with a previous cancer diagnosis. The changing demographics of our patient population will make this quandary more common. Previous guidance has emphasised the importance of lengthy postcancer drug holidays and cautious use of IBD therapies. However, accumulating evidence suggests this approach may be unnecessarily conservative. This review considers recent evidence on the safety of IBD drugs, cancer and recurrent cancer risk in patients with IBD and provides a framework for shared decision making involving patient, gastroenterologist and oncologist.
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Affiliation(s)
| | - Zara Aiken
- Department of Medicine, St John's Hospital, NHS Lothian, Livingston, UK
| | - Shien Chow
- Department of Oncology, Clatterbridge Cancer Centre NHS Foundation Trust, Bebington, UK
| | - Shahida Din
- Gastroenterology Unit, NHS Lothian, Edinburgh, UK
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20
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Yield and Predictors of Surveillance Colonoscopies in Older Adults With Long-standing Ulcerative Colitis. Clin Gastroenterol Hepatol 2022; 20:e1353-e1364. [PMID: 34425278 DOI: 10.1016/j.cgh.2021.08.019] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/20/2021] [Revised: 08/11/2021] [Accepted: 08/13/2021] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Although colonoscopies for dysplasia surveillance are standard of care in patients with long-standing ulcerative colitis (UC), there is a paucity of data on the yield of surveillance colonoscopies in those older than 75 years of age. METHODS We conducted a multicenter retrospective cohort study including patients with UC who underwent ≥1 colonoscopy at age ≥75 years. The primary outcome was diagnosis of dysplasia (visible or random) and colorectal cancer. Multivariable regression adjusted for relevant confounders examined the predictors of polypoid or non-polypoid dysplasia or colorectal cancer. RESULTS The primary cohort included 211 patients with UC who underwent 635 colonoscopies after age ≥75 years. A total of 83 patients (39.3%) patients had dysplasia or cancer detected. Among colonoscopies, 123 (19.4%) identified visible dysplasia, 23 (3.6%) had random dysplasia (1 high-grade dysplasia found in each group, respectively), and 5 (0.8%) had colon cancer. In multivariable analysis, prior adenoma or colon cancer below age 75 tears (odds ratio [OR], 2.06; 95% confidence interval [CI], 1.07-3.96), flat dysplasia before 75 years (OR, 2.78; 95% CI, 1.05-7.44), and older age (80-84 years (OR, 2.29; 95% CI, 1.20-4.38), ≥85 years (OR, 3.54; 95% CI, 1.27-9.82) were associated with detection of dysplasia or cancer. Only 1 patient was noted to have a procedure-related complication. CONCLUSIONS Patients with long-standing UC without prior dysplasia may have a low yield on continued endoscopic surveillance at age ≥75 years. A targeted approach to surveillance may be appropriate in older individuals with UC.
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21
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Cumbo C, Tarantini F, Zagaria A, Anelli L, Minervini CF, Coccaro N, Tota G, Impera L, Parciante E, Conserva MR, Redavid I, Carluccio P, Delia M, Giordano A, Longo MC, Perrone T, Rossi AR, Specchia G, Musto P, Albano F. Clonal Hematopoiesis at the Crossroads of Inflammatory Bowel Diseases and Hematological Malignancies: A Biological Link? Front Oncol 2022; 12:873896. [PMID: 35494055 PMCID: PMC9039212 DOI: 10.3389/fonc.2022.873896] [Citation(s) in RCA: 12] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2022] [Accepted: 03/21/2022] [Indexed: 12/23/2022] Open
Abstract
Inflammatory bowel diseases (IBDs) are a group of chronic conditions of the gastrointestinal tract in which nationwide studies have revealed a higher risk of hematological malignancies (HMs). Clonal hematopoiesis (CH) is a premalignant condition defined by the presence of an acquired somatic mutation characterized by a variant allele frequency (VAF) of ≥2%, in a gene frequently associated with HMs. A growing body of evidence suggests a correlation between inflammation and CH; its occurrence in the context of IBD has been previously demonstrated. With the aim to assess CH possible co-occurrence in patients with an IBD associated with HMs, we performed a targeted next-generation sequencing analysis in a cohort of thirteen patients who were referred to our center with IBD associated with HMs. Eleven (85%) patients showed one or more mutations in CH-associated genes; DNMT3A was the most frequently mutated gene, followed by ASXL1 and JAK2. These results may suggest that the mechanisms at the basis of the inflammatory environment could potentially select for the growth of hematopoietic clones harboring specific mutations. In this context, CH emergence may be boosted by the proinflammatory IBD environment, thus acting as a biological link between IBD and the HM onset. If these data are confirmed, IBD patients screened and positive for CH should undergo a hematologic follow-up to assess the risk of developing HM. Future study will clarify the relationship between these conditions.
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Affiliation(s)
- Cosimo Cumbo
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Francesco Tarantini
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Antonella Zagaria
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Luisa Anelli
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Crescenzio Francesco Minervini
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Nicoletta Coccaro
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Giuseppina Tota
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Luciana Impera
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Elisa Parciante
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Maria Rosa Conserva
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Immacolata Redavid
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Paola Carluccio
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Mario Delia
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Annamaria Giordano
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Maria Chiara Longo
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Tommasina Perrone
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Antonella Russo Rossi
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | | | - Pellegrino Musto
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
| | - Francesco Albano
- Department of Emergency and Organ Transplantation (D.E.T.O.), Hematology and Stem Cell Transplantation Unit, University of Bari "Aldo Moro", Bari, Italy
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22
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Wang JH, D’Arcy M, Barnes EL, Freedman ND, Engels EA, Song M. Associations of Inflammatory Bowel Disease and Subsequent Cancers in a Population-Based Study of Older Adults in the United States. JNCI Cancer Spectr 2022; 6:pkab096. [PMID: 35071980 PMCID: PMC8767622 DOI: 10.1093/jncics/pkab096] [Citation(s) in RCA: 9] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/02/2021] [Revised: 10/08/2021] [Accepted: 10/27/2021] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Cancer risk is elevated in patients with inflammatory bowel disease (IBD). A comprehensive investigation of cancer risk in older patients (≥66 years of age) is needed, because this understudied population is at high risk. METHODS We performed a case-control study using Surveillance Epidemiology and End Results-Medicare data including 1 986 735 incident cancer cases (aged 66-99 years; diagnosed 1992-2015) and 200 000 controls matched by sex, age, race and ethnicity, and selection year. IBD was identified by ulcerative colitis (UC) or Crohn's disease (CD) diagnosis codes. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated with logistic regression, adjusting for potential confounders. For colorectal cancers, we further adjusted for screening rates. We assessed confounding by medication exposure among patients with prescription drug coverage. RESULTS IBD, CD, and UC were present in 0.8%, 0.3%, and 0.5% in both cancer cases and non-cancer controls. Of 51 cancers examined, IBD was statistically significantly associated with cancers of the small intestine (OR = 2.55, 95% CI = 2.15 to 3.01), intrahepatic (OR = 1.92, 95% CI = 1.47 to 2.51) and extrahepatic bile ducts (OR = 1.75, 95% CI = 1.38 to 2.22), rectum (OR = 1.61, 95% CI = 1.36 to 1.90), and colon (OR = 1.21, 95% CI = 1.10 to 1.33). CD was associated with cancers of the small intestine (OR = 4.55, 95% CI = 3.65 to 5.67), and UC was associated with cancers of the intrahepatic bile ducts (OR = 1.87, 95% CI = 1.34 to 2.61), rectum (OR = 1.80, 95% CI = 1.47 to 2.20), and colon (OR = 1.28, 95% CI = 1.14 to 1.43). After adjusting for medication exposure, IBD was not statistically significantly associated with lung cancer, melanoma, diffuse large B-cell lymphoma, and myelodysplastic syndrome. CONCLUSIONS In this large study among older adults (≥66 years of age), IBD was positively associated with gastrointestinal cancers. Associations with extraintestinal cancers may reflect the effect of immunosuppressive medications.
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Affiliation(s)
- Jeanny H Wang
- Division of Cancer Epidemiology and Genetics, Infections and Immunoepidemiology Branch, National Cancer Institute, Rockville, MD, USA
| | - Monica D’Arcy
- Division of Cancer Epidemiology and Genetics, Biostatistics Branch, National Cancer Institute, Rockville, MD, USA
| | - Edward L Barnes
- Division of Gastroenterology and Hepatology, Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Multidisciplinary Center for Inflammatory Bowel Diseases, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
- Center for Gastrointestinal Biology and Disease, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA
| | - Neal D Freedman
- Division of Cancer Epidemiology and Genetics, Metabolic Epidemiology Branch, National Cancer Institute, Rockville, MD, USA
| | - Eric A Engels
- Division of Cancer Epidemiology and Genetics, Infections and Immunoepidemiology Branch, National Cancer Institute, Rockville, MD, USA
| | - Minkyo Song
- Division of Cancer Epidemiology and Genetics, Infections and Immunoepidemiology Branch, National Cancer Institute, Rockville, MD, USA
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Gong C, Xu R, Zou P, Zhang Y, Wang X. Inflammatory bowel disease and risk of breast cancer: a meta-analysis of cohort studies. Eur J Cancer Prev 2022; 31:54-63. [PMID: 34871199 DOI: 10.1097/cej.0000000000000667] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Abstract
Inflammatory bowel disease (IBD) has been found to be correlated to increased risk of both gastrointestinal and extraintestinal malignancies. It still remains conflicting whether IBD has influence on risk of breast cancer, requesting further investigations. A systematic literature research before June 2020 was conducted in PubMed and Web of Science databases. Observational studies reporting incident breast cancer after IBD diagnosis and providing measures of association were included in the meta-analysis. The pooled odds ratio (OR) with 95% confidence interval (CI) was calculated to evaluate the associations between IBD and risk of breast cancer. Our analysis included 16 cohort studies and the overall pooled OR in patients with IBD was 0.94 (95% CI, 0.82-1.06). In further subgroup analysis, no significant association with breast cancer risk among patients with Crohn's disease (OR, 0.91; 95% CI, 0.70-1.12) and ulcerative colitis (OR, 0.99; 95% CI, 0.90-1.08). For geographic differences, the summary OR of populations in Asia (OR, 1.01; 95% CI, 0.73-1.30) was only numerically larger than that in European populations (OR, 0.90; 95% CI, 0.75-1.06). Our findings indicated that IBD had no significant influence on breast cancer risk regardless of different IBD types and geographical areas.
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Affiliation(s)
- Can Gong
- Department of Breast Surgery, West China Hospital, Sichuan University
| | - Renyuan Xu
- Department of Breast Surgery, West China Hospital, Sichuan University
| | - Ping Zou
- Department of Breast Surgery, The People's Hospital of Pengzhou, Chengdu, Sichuan Province, China
| | - Yuna Zhang
- Department of Breast Surgery, West China Hospital, Sichuan University
| | - Xiaodong Wang
- Department of Breast Surgery, West China Hospital, Sichuan University
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24
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Wang Z, Zhang H, Yang H, Zhang M, Qian J. The Incidence Rate and Risk Factors of Malignancy in Elderly-Onset Inflammatory Bowel Disease: A Chinese Cohort Study From 1998 to 2020. Front Oncol 2021; 11:788980. [PMID: 34956904 PMCID: PMC8695610 DOI: 10.3389/fonc.2021.788980] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/04/2021] [Accepted: 11/16/2021] [Indexed: 12/12/2022] Open
Abstract
Background Patients suffering from inflammatory bowel disease (IBD) have an increased risk of cancer. However, the risk of malignancy in patients with elderly-onset IBD (≥60 years) remains controversial. Hence, we aimed to identify and compare the dissimilarities in morbidity and related risk factors between patients with elderly-onset and adult-onset (18–59 years) IBD in a Chinese cohort. Methods Patients with confirmed IBD, diagnosed at age ≥18 years, between January 1998 and December 2020 at the Peking Union Medical College Hospital were enrolled. The yearly incidence rates (IRs) for cancer were calculated, and the characteristics were analyzed in these patients. Results A total of 1,480 patients suffering from adult-onset IBD and 129 patients suffering from elderly-onset IBD with a median follow-up period of 4.9 years and 4.8 years, respectively, were included. Patients in the elderly-onset IBD group demonstrated an increased overall incidence of cancer than that demonstrated by patients in the adult-onset group (IR 26.9 versus 9.51, respectively, per 1,000 person-years; relative risk [RR], 2.83). Colorectal cancer was the most common malignancy in the two groups, and patients suffering from elderly-onset IBD demonstrated a higher incidence of the malignancy (IR, 7.07 versus 3.34, respectively, per 1,000 person-years; RR, 2.12). Among the extraintestinal cancers, hematological malignancies and urinary tract cancers (including renal and urinary bladder carcinoma) were common in the elderly-onset group (IR, 4.24 and 4.24 per 1,000 person-years, respectively), whereas thyroid cancer was more common in the adult-onset group (IR, 1.36 per 1,000 person-years). Analysis of clinical characteristics revealed that patients with elderly-onset IBD who developed cancer were more likely to have diabetes and urinary lithiasis (p = 0.041 and 0.035, respectively). In addition, patients in the elderly-onset group had a shorter course from IBD to cancer, less exposure to immunosuppressants, less extraintestinal manifestations, and higher cancer-related mortality. Cox proportional risk regression analysis in the elderly-onset IBD group revealed that diabetes was an independent risk factor for the progression to cancer (hazard ratio [HR], 12.53 [2.379–65.994], P = 0.003). Conclusion The risk of malignancy in patients suffering from elderly-onset IBD increased significantly as compared with those with adult-onset disease. Therefore, cancer monitoring should be initiated earlier for patients in the elderly-onset group.
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Affiliation(s)
- Zheng Wang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Huimin Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Yang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mengmeng Zhang
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Jiaming Qian
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
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25
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Mala A, Foteinogiannopoulou K, Koutroubakis IE. Solid extraintestinal malignancies in patients with inflammatory bowel disease. World J Gastrointest Oncol 2021; 13:1956-1980. [PMID: 35070035 PMCID: PMC8713323 DOI: 10.4251/wjgo.v13.i12.1956] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/09/2021] [Revised: 07/06/2021] [Accepted: 08/13/2021] [Indexed: 02/06/2023] Open
Abstract
Malignancies constitute the second cause of death in patients with inflammatory bowel diseases (IBD), after cardiovascular diseases. Although it has been postulated that IBD patients are at greater risk of colorectal cancer compared to the general population, lately there has been evidence supporting that this risk is diminishing over time as a result of better surveillance, while the incidence of extraintestinal cancers (EICs) is increasing. This could be attributed either to systemic inflammation caused by IBD or to long-lasting immunosuppression due to IBD treatments. It seems that the overall risk of EICs is higher for Crohn’s disease patients and it is mainly driven by skin cancers, and liver-biliary cancers in patients with IBD and primary sclerosing cholangitis. The aims of this review were first to evaluate the prevalence, characteristics, and risk factors of EICs in patients with IBD and second to raise awareness regarding a proper surveillance program resulting in early diagnosis, better prognosis and survival, especially in the era of new IBD treatments that are on the way.
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Affiliation(s)
- Anastasia Mala
- Department of Medical Oncology, University Hospital of Heraklion, Heraklion 71110, Crete, Greece
| | | | - Ioannis E Koutroubakis
- Department of Gastroenterology, University Hospital of Heraklion, Heraklion 71110, Crete, Greece
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26
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Efetov SK, Kitsenko YE, Shchervyanina DA, Minenkova AG, Tulina IA, Tsarkov PV. Total proctocolectomy with ileal pouch-anal anastomosis and D3 lymph node dissection with inflammatory bowel disease associated colon cancer - a video vignette. Colorectal Dis 2021; 23:2786-2787. [PMID: 34272805 DOI: 10.1111/codi.15820] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 06/09/2021] [Accepted: 07/11/2021] [Indexed: 02/08/2023]
Affiliation(s)
- Sergey K Efetov
- I.M. Sechenov First Moscow State Medical University, Sechenov University, Moscow, Russia
| | - Yurii E Kitsenko
- I.M. Sechenov First Moscow State Medical University, Sechenov University, Moscow, Russia
| | - Dariia A Shchervyanina
- I.M. Sechenov First Moscow State Medical University, Sechenov University, Moscow, Russia
| | - Alisa G Minenkova
- I.M. Sechenov First Moscow State Medical University, Sechenov University, Moscow, Russia
| | - Inna A Tulina
- I.M. Sechenov First Moscow State Medical University, Sechenov University, Moscow, Russia
| | - Petr V Tsarkov
- I.M. Sechenov First Moscow State Medical University, Sechenov University, Moscow, Russia
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27
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Abstract
New data suggest that incidence and prevalence of inflammatory bowel diseases [IBD] are still increasing worldwide, and approximately 0.2% of the European population suffer from IBD at the present time. Medical therapy and disease management have evolved significantly in recent decades, with an emphasis on tight objective monitoring of disease progression and a treat-to-target approach in Europe and also worldwide, aiming to prevent early bowel damage and disability. Surgery rate declined over time in Europe, with 10-30% of CD and 5-10% of UC patients requiring a surgery within 5 years. The health economic burden associated with IBD is high in Europe. Direct health care costs [approximately €3500 in CD and €2000 in UC per patient per year] have shifted from hospitalisation and surgery towards drug-related expenditures with the increasing use of biologic therapy and other novel agents, and substantial indirect costs arise from work productivity loss [approximately €1900 per patient yearly]. The aim of this paper is to provide an updated review of the burden of IBD in Europe by discussing current data on epidemiology, disease course, risk for surgery, hospitalisation, and mortality and cancer risks, as well as the economic aspects, patient disability, and work impairment, by discussing the latest population-based studies from the region.
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Affiliation(s)
- Mirabella Zhao
- Gastro Unit, Medical Division, Hvidovre University Hospital, Hvidovre, Denmark
| | - Lóránt Gönczi
- First Department of Medicine, Semmelweis University, Budapest, Hungary
| | - Peter L Lakatos
- First Department of Medicine, Semmelweis University, Budapest, Hungary
- McGill University Health Centre, Montreal General Hospital, Montreal, QC, Canada
| | - Johan Burisch
- Gastro Unit, Medical Division, Hvidovre University Hospital, Hvidovre, Denmark
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28
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Lee JW, Kim ES. Is the Long-term Disease Course of Elderly-Onset Ulcerative Colitis Different from That of Non-Elderly-Onset Ulcerative Colitis? Gut Liver 2021; 15:639-640. [PMID: 34521775 PMCID: PMC8444109 DOI: 10.5009/gnl210403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Affiliation(s)
- Jin Wook Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea
| | - Eun Soo Kim
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Korea
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29
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Zhu M, Ran Z. Clinical characteristics of ulcerative colitis in elderly patients. JGH Open 2021; 5:849-854. [PMID: 34386591 PMCID: PMC8341179 DOI: 10.1002/jgh3.12612] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/20/2021] [Revised: 06/27/2021] [Accepted: 07/01/2021] [Indexed: 12/18/2022]
Abstract
The incidence of ulcerative colitis (UC) in elderly patients is increasing. Elderly UC patients are likely to exhibit distinct features both at diagnosis and during follow-up. Age-related problems, including complications, immune dysfunction, and multidrug use, make the diagnosis and treatment of elderly UC more challenging. Suboptimal treatment considering adverse events leads to poor clinical outcome in elderly UC patients. Here, we reviewed the epidemiology, clinical presentation, medical therapy, colorectal cancer surveillance of UC in elderly patients.
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Affiliation(s)
- Mingming Zhu
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of MedicineShanghai Jiao Tong University, Shanghai Jiao Tong University; Shanghai Institute of Digestive DiseaseShanghaiChina
| | - Zhihua Ran
- Division of Gastroenterology and Hepatology, Key Laboratory of Gastroenterology and Hepatology, Ministry of Health, Shanghai Inflammatory Bowel Disease Research Center, Renji Hospital, School of MedicineShanghai Jiao Tong University, Shanghai Jiao Tong University; Shanghai Institute of Digestive DiseaseShanghaiChina
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30
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Hong SJ, Katz S. The elderly IBD patient in the modern era: changing paradigms in risk stratification and therapeutic management. Therap Adv Gastroenterol 2021; 14:17562848211023399. [PMID: 34276809 PMCID: PMC8255562 DOI: 10.1177/17562848211023399] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/14/2020] [Accepted: 05/20/2021] [Indexed: 02/04/2023] Open
Abstract
The incidence and prevalence of inflammatory bowel disease (IBD) is rising in the elderly population. Compared with patients with onset during their younger years, patients with elderly onset IBD have a distinct clinical presentation, disease phenotype, and natural history. Genetics contribute less to pathogenesis of disease, whereas biological changes associated with aging including immunosenescence, dysbiosis, and frailty have a greater impact on disease outcomes. With the advent of an increasingly wider array of biologic and small-molecule therapeutic options, data regarding efficacy and safety of these agents in elderly IBD patients specifically are paramount, given the unique characteristics of this population.
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Affiliation(s)
- Simon J. Hong
- Inflammatory Bowel Disease Center at New York University Langone Health, Division of Gastroenterology and Hepatology, 305 East 33rd Street, New York, NY 10016-4576, USA
| | - Seymour Katz
- Inflammatory Bowel Disease Center at New York University Langone Health, Division of Gastroenterology and Hepatology, New York, NY, USA
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31
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Lo B, Zhao M, Vind I, Burisch J. The Risk of Extraintestinal Cancer in Inflammatory Bowel Disease: A Systematic Review and Meta-analysis of Population-based Cohort Studies. Clin Gastroenterol Hepatol 2021; 19:1117-1138.e19. [PMID: 32801010 DOI: 10.1016/j.cgh.2020.08.015] [Citation(s) in RCA: 57] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/24/2020] [Revised: 07/27/2020] [Accepted: 08/05/2020] [Indexed: 02/07/2023]
Abstract
BACKGROUND & AIMS Patients with Crohn's disease (CD) and ulcerative colitis (UC) are at increased risk of developing intestinal cancer. However, less is known about the risk of extraintestinal cancers (EICs). The aim of this study was to conduct a systematic review and meta-analysis of population-based cohorts assessing the risk of EICs in inflammatory bowel disease (IBD) patients. METHODS Only population-based studies reporting on the prevalence or incidence of EICs were included. In total, 884 studies were screened and those included were assessed for quality. Eligible studies were pooled for length of follow-up evaluation, events in the IBD population, and events or expected events in a control population for the meta-analyses. RESULTS In total, 40 studies were included in the systematic review and 15 studies were included in the meta-analysis. The overall risk of EICs was found to be increased in both CD (incidence rate ratio [IRR]: 1.43 [CI, 1.26, 1.63]) and UC (IRR: 1.15 [1.02, 1.31]) patients. Both CD and UC patients presented with an increased risk of skin (IRR: CD, 2.22 [1.41-3.48]; UC, 1.38 [1.12-1.71]) and hepatobiliary (IRR: CD, 2.31 [1.25-4.28]; UC, 2.05 [1.52-2.76]) malignancies. Furthermore, CD patients showed an increased risk of hematologic (IRR, 2.40 [1.81-3.18]) and lung (IRR, 1.53 [1.23-1.91]) cancers. These increased risks were present despite treatment with immunosuppressives. CONCLUSIONS This systematic review and meta-analysis shows that both CD and UC patients are at an increased risk of developing EICs, both overall and at specific sites. However, additional studies with longer follow-up evaluation are needed to assess the true risk of EICs posed by IBD.
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Affiliation(s)
- Bobby Lo
- Gastrounit, Medical Section, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark.
| | - Mirabella Zhao
- Gastrounit, Medical Section, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Ida Vind
- Gastrounit, Medical Section, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
| | - Johan Burisch
- Gastrounit, Medical Section, Copenhagen University Hospital Hvidovre, Hvidovre, Denmark
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Inflammatory bowel disease and risk of gastric, small bowel and colorectal cancer: a meta-analysis of 26 observational studies. J Cancer Res Clin Oncol 2021; 147:1077-1087. [PMID: 33433655 DOI: 10.1007/s00432-020-03496-0] [Citation(s) in RCA: 34] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/25/2020] [Accepted: 12/02/2020] [Indexed: 02/07/2023]
Abstract
PURPOSE The purpose of this meta-analysis was to assess the associations between inflammatory bowel disease (IBD) and risk of the gastric, small bowel and colorectal cancer. METHODS We searched the PubMed and Web of Science for observational studies published before June 2020, and the quality of each included study was evaluated according to the Newcastle-Ottawa-Scale. RESULTS Twenty-six studies comprising 531 449 IBD patients and more than 65 million reference individuals were included. Although IBD was significantly associated with 67% increased risk of the total gastric, small bowel and colorectal cancer. After stratifying by cancer location, IBD mainly increased the risk of intestinal cancer instead of gastric cancer. Furthermore, Crohn's disease (CD) significantly increased the risk of both small bowel cancer and colorectal cancer, while ulcerative colitis (UC) only increased the risk of colorectal cancer. In subgroup analysis, associations between IBD and risk of total gastric, small bowel and colorectal cancer were similar between male and female, except for that male IBD patients but not female had a significantly higher risk of small bowel cancer. Additionally, IBD patients in different geographical areas had different associations with risk of various gastrointestinal tract cancers. CONCLUSIONS IBD is mainly associated with increased risk of cancers in the lower gastrointestinal tract, including small bowel cancer and colorectal cancer. Because studies about the association between IBD and risk of gastric cancer and the populations in Asia are limited, more observational studies are required in the future.
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Rozich JJ, Dulai PS, Fumery M, Sandborn WJ, Singh S. Progression of Elderly Onset Inflammatory Bowel Diseases: A Systematic Review and Meta-Analysis of Population-Based Cohort Studies. Clin Gastroenterol Hepatol 2020; 18:2437-2447.e6. [PMID: 32142940 PMCID: PMC7490750 DOI: 10.1016/j.cgh.2020.02.048] [Citation(s) in RCA: 42] [Impact Index Per Article: 8.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/18/2019] [Revised: 02/18/2020] [Accepted: 02/22/2020] [Indexed: 02/06/2023]
Abstract
BACKGROUND & AIMS The incidence of inflammatory bowel diseases (IBDs) in older adults is increasing. We performed a systematic review and meta-analysis to evaluate progression of elderly onset (EO) IBD in population-based cohorts and compared it with adult onset (AO) IBD. METHODS In a systematic review through June 1, 2019, we identified population-based cohort studies of EO IBD reporting the cumulative risk of hospitalization, surgery, mortality, treatment patterns, escalation, and/or malignancy. Data were synthesized using random-effects meta-analysis as cumulative risk of events at 1 year, 5 years, and 10 years, and compared with data from patients with AO IBD in the same cohorts. RESULTS We identified 9 studies, comprising 14,765 patients with EO IBD. In patients with EO Crohn's disease (CD), the cumulative 5-year risk of surgery was 22.6% (95% CI, 18.7-27.2) and was similar to that of patients with AO CD (relative risk [RR], 1.04; 95% CI, 0.80-1.34). Overall exposure to corticosteroids was comparable between patients with EO CD vs AO CD (5-year risk: 55.4%; 95% CI, 53.4-57.4; RR, 0.88; 95% CI, 0.78-1.00), but exposure to immunomodulators (31.5%; 95% CI, 29.7-33.4; RR, 0.62; 95% CI, 0.51-0.77) or biologic agents (6.5%; 95% CI, 5.6-7.6; RR, 0.36; 95% CI, 0.25-0.52) was significantly lower for patients with EO CD than for patients with AO CD. Similarly, in patients with EO ulcerative colitis (UC), the cumulative 5-year risk of surgery was 7.8% (95% CI, 5.0-12.0), similar to the risk for patients with AO UC (RR, 1.29; 95% CI, 0.79-2.11). Overall exposure to corticosteroids was comparable between patients with EO UC vs AO UC (5-year risk: 57.2%; 95% CI, 55.6-58.7; RR, 0.98; 95% CI, 0.91-1.06), but exposure to immunomodulators (16.1%; 95% CI, 15.0-17.2; RR, 0.58; 95% CI, 0.54-0.62) or biologic agents (2.0%; 95% CI, 1.6-2.5; RR, 0.36; 95% CI, 0.24-0.52) was significantly lower for patients with EO UC than for patients with AO UC. Patients with EO IBD appeared to have increased mortality, but not malignancy, compared with the general population. There were few data on comorbidities or adverse effects of medications. CONCLUSIONS In a systematic review and meta-analysis, we found that patients with EO IBD have a similar risk of surgery as patients with AO IBD. However, patients with EO IBD are less likely to receive treatment with immunomodulators or biologic agents.
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Affiliation(s)
- Jacob J. Rozich
- Department of Internal Medicine, University of California
San Diego, La Jolla, California
| | - Parambir S. Dulai
- Division of Gastroenterology, University of California San
Diego, La Jolla, California
| | - Mathurin Fumery
- Gastroenterology Unit, Amiens University and Hospital,
Université de Picardie Jules Verne, Amiens, France
| | - William J. Sandborn
- Division of Gastroenterology, University of California San
Diego, La Jolla, California
| | - Siddharth Singh
- Division of Gastroenterology; Division of Biomedical Informatics, University of California San Diego, La Jolla, California.
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Bak M, Jess T, Flachs EM, Zwisler AD, Juel K, Frederiksen H. Risk of Inflammatory Bowel Disease in Patients with Chronic Myeloproliferative Neoplasms: A Danish Nationwide Cohort Study. Cancers (Basel) 2020; 12:cancers12092700. [PMID: 32967227 PMCID: PMC7564361 DOI: 10.3390/cancers12092700] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/01/2020] [Revised: 08/14/2020] [Accepted: 08/19/2020] [Indexed: 01/18/2023] Open
Abstract
Simple Summary We wanted to investigate the risk of inflammatory bowel disease (IBD) in patients with Philadelphia-negative chronic myeloproliferative neoplasms (MPNs), since up to 50% of these patients experience gastrointestinal symptoms and several studies have suggested an association between hematological cancers and IBD. We included ∼8000 patients and ∼80,000 sex- and age-matched, non-MPN comparisons from the general population, and found that MPN patients were two to three times more likely to develop IBD, but the absolute risk of IBD was modest. In addition, MPN patients were also 40% more likely to have a prior diagnosis of IBD. Our results pose intriguing questions about the causal pathways linking MPN and IBD, which may include genetic, treatment-related and immune-mediated factors. Moreover, it shows that abdominal symptoms in MPN patients may not only be caused by an enlarged spleen or treatment side-effects. Conversely, persistent leucocytosis and/or increased platelets in IBD patients may reflect concomitant MPN. Abstract An association between hematological cancers and inflammatory bowel disease (IBD) has previously been suggested, but the risk of IBD in patients with myeloproliferative neoplasms (MPNs) is unknown. We conducted a nationwide population-based cohort study using Danish registries, to estimate the risk of IBD in individuals diagnosed with essential thrombocythemia, polycythemia vera, myelofibrosis or unclassifiable MPN during 1994–2013. MPN patients were matched 1:10 with sex- and age-matched comparisons. Everyone was followed until a diagnosis of IBD, death/emigration, or 31 December 2013. The risk of IBD overall and according to MPN subtype was calculated using Cox regression and presented as hazard ratios (HRs) with 95% confidence intervals (CI). Of 8207 MPN patients followed for 45,232 person-years, 80 were diagnosed with IBD (61 ulcerative colitis, 19 Crohn’s disease). The rate of IBD per 1000 person-years was 1.8 (95% CI:1.4–2.2) in patients vs. 0.8 (95% CI:0.7–0.8) in comparisons, and the absolute 10-year risk of IBD was 0.8% (95% CI:0.6–1.0) in patients vs. 0.4% (95% CI:0.4–0.5) in comparisons. The HR of IBD was 2.4 (95% CI:2.1–2.9) with similar HRs for ulcerative colitis and Crohn’s disease. MPN subtype risks varied from 2.1 (95% CI:1.6–2.7) to 2.8 (95% CI:2.1–3.7). Our unselected cohort study showed a more than 2-fold increased risk of IBD in MPN patients.
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Affiliation(s)
- Marie Bak
- Department of Haematology, Zealand University Hospital, University of Copenhagen, 4000 Roskilde, Denmark
- Correspondence: ; Tel.: +45-47324894
| | - Tine Jess
- Department of Epidemiology Research, Statens Serum Institut, 2300 Copenhagen, Denmark;
| | - Esben Meulengracht Flachs
- Department of Occupational and Environmental Medicine, Bispebjerg Hospital, University of Copenhagen, 2400 Copenhagen, Denmark;
| | - Ann-Dorthe Zwisler
- Danish Knowledge Centre for Rehabilitation and Palliative Care, University of Southern Denmark and Odense University Hospital, 5800 Nyborg, Denmark;
| | - Knud Juel
- National Institute of Public Health, University of Southern Denmark, 1455 Copenhagen, Denmark;
| | - Henrik Frederiksen
- Department of Haematology, Odense University Hospital, 5000 Odense, Denmark;
- Department of Clinical Epidemiology, Aarhus University Hospital, 8200 Aarhus, Denmark
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Piovani D, Danese S, Peyrin-Biroulet L, Nikolopoulos GK, Bonovas S. Systematic review with meta-analysis: biologics and risk of infection or cancer in elderly patients with inflammatory bowel disease. Aliment Pharmacol Ther 2020; 51:820-830. [PMID: 32170782 DOI: 10.1111/apt.15692] [Citation(s) in RCA: 51] [Impact Index Per Article: 10.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 12/18/2019] [Revised: 01/13/2020] [Accepted: 02/27/2020] [Indexed: 12/14/2022]
Abstract
BACKGROUND Uncertainty exists concerning the risk of infection and cancer associated with biologic therapies in elderly patients with inflammatory bowel disease (IBD). AIMS To identify, synthesise and critically appraise the available evidence on the topic. METHODS We systematically searched Medline/PubMed, Embase and Scopus, through October 2019, and recent conference proceedings, to identify studies investigating the risk of serious infections, opportunistic infections, any infection and cancer in elderly IBD patients (>60 years) exposed to biologics as compared to those unexposed to biologics. Two reviewers independently extracted study data and assessed each study's risk of bias. We examined heterogeneity, and calculated summary effect estimates using fixed- and random effects models. Quality of evidence was determined with GRADE. RESULTS We included 15 studies (one post hoc analysis of a randomised trial, nine cohort and five case-control studies). Elderly IBD patients treated with biologics were at increased risk of developing serious infections (random effects summary relative risk: 2.70, 95% CI: 1.56-4.66; seven studies; I2 = 57%) and opportunistic infections (3.16, 1.09-9.20; four studies; I2 = 73%). The occurrence of any infection (1.67, 0.51-5.43; five studies; I2 = 75%) and cancer (0.90, 0.64-1.26; nine studies; I2 = 0%) was not significantly affected. Nevertheless, our confidence in the effect estimates is rather limited; the quality of evidence is low to very low. CONCLUSIONS Biologics are likely to increase the risk of serious and opportunistic infections in old IBD patients. Large prospective studies are needed to further assess the biologic treatments' long-term safety profile in this population.
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Affiliation(s)
- Daniele Piovani
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,IBD Center, Humanitas Clinical and Research Center - IRCCS, Milan, Italy
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,IBD Center, Humanitas Clinical and Research Center - IRCCS, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology, Nancy University Hospital, University of Lorraine, Vandoeuvre-lès-Nancy, France
| | | | - Stefanos Bonovas
- Department of Biomedical Sciences, Humanitas University, Milan, Italy.,IBD Center, Humanitas Clinical and Research Center - IRCCS, Milan, Italy
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Singh S, Picardo S, Seow CH. Management of Inflammatory Bowel Diseases in Special Populations: Obese, Old, or Obstetric. Clin Gastroenterol Hepatol 2020; 18:1367-1380. [PMID: 31712084 PMCID: PMC7183892 DOI: 10.1016/j.cgh.2019.11.009] [Citation(s) in RCA: 32] [Impact Index Per Article: 6.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/14/2019] [Revised: 10/25/2019] [Accepted: 11/04/2019] [Indexed: 02/07/2023]
Abstract
The epidemiology of inflammatory bowel disease (IBD) is progressively evolving impacting the type of patients with IBD we will see in clinical practice. In this review, we discuss specific challenges and solutions in the management of (1) obese, (2) older and (3) obstetric (pregnant) patients with IBD. With the global obesity epidemic, almost 1 in 3 patients with IBD are obese. Obesity is associated with greater difficulty in achieving remission, higher risk of disease relapse and higher burden and costs of hospitalization in patients with IBD. Obese patients also have inferior response to biologic therapy related to altered pharmacokinetics and obesity-mediated chronic inflammation. Surgical management of obese patients with IBD is also challenging. Similar to obesity, the prevalence of IBD in older patients is rising and it is anticipated that almost one-third of patients with IBD will be older than 60 years within the next decade. Older patients present unique diagnostic and therapeutic dilemmas, and management of these individuals warrants careful consideration of the risks of disease-related versus treatment-related complications, non-IBD-related extra-intestinal complications (eg, cardiovascular disease, malignancy), in the context of individual values, preferences, functional status and comorbidities. With evolving therapeutics, medical management of IBD surrounding pregnancy continues to be challenging. Overall, the management of pregnant patients requires a pro-active, multidisciplinary approach, with an emphasis on optimal disease control not just during, but prior to pregnancy. This often involves continuation of highly effective therapies, of which the vast majority are safe during pregnancy and breastfeeding, resulting in a reduction of risk of adverse maternal fetal outcomes.
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Affiliation(s)
- Siddharth Singh
- Division of Gastroenterology, University of California San Diego, La Jolla, California; Division of Biomedical Informatics, University of California San Diego, La Jolla, California.
| | - Sherman Picardo
- Inflammatory Bowel Disease Centre, Department of Gastroenterology, University of Calgary, Calgary, Alberta, Canada
| | - Cynthia H. Seow
- Inflammatory Bowel Disease Centre, Department of Gastroenterology, University of Calgary, Calgary, Alberta, Canada,Department of Community Health Sciences, University of Calgary, Calgary, Alberta, Canada
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Olén O, Askling J, Sachs MC, Neovius M, Smedby KE, Ekbom A, Ludvigsson JF. Mortality in adult-onset and elderly-onset IBD: a nationwide register-based cohort study 1964-2014. Gut 2020; 69:453-461. [PMID: 31092591 DOI: 10.1136/gutjnl-2018-317572] [Citation(s) in RCA: 66] [Impact Index Per Article: 13.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/11/2018] [Revised: 04/09/2019] [Accepted: 04/30/2019] [Indexed: 12/13/2022]
Abstract
OBJECTIVES To examine all-cause and cause-specific mortality in adult-onset and elderly-onset IBD and to describe time trends in mortality over the past 50 years. DESIGN Swedish nationwide register-based cohort study 1964-2014, comparing mortality in 82 718 incident IBD cases (inpatient and non-primary outpatient care) with 10 times as many matched general population reference individuals (n=801 180) using multivariable Cox regression to estimate HRs. Among patients with IBD, the number of participants with elderly-onset (≥60 years) IBD was 17 873. RESULTS During 984 330 person-years of follow-up, 15 698/82 718 (19%) of all patients with IBD died (15.9/1000 person-years) compared with 121 095/801 180 (15.1%) of reference individuals, corresponding to an HR of 1.5 for IBD (95% CI=1.5 to 1.5 (HR=1.5; 95% CI=1.5 to 1.5 in elderly-onset IBD)) or one extra death each year per 263 patients. Mortality was increased specifically for UC (HR=1.4; 95% CI=1.4 to 1.5), Crohn's disease (HR=1.6; 95% CI=1.6 to 1.7) and IBD-unclasssified (HR=1.6; 95% CI=1.5 to 1.8). IBD was linked to increased rates of multiple causes of death, including cardiovascular disease (HR=1.3; 1.3 to 1.3), malignancy (HR=1.4; 1.4 to 1.5) and digestive disease (HR=5.2; 95% CI=4.9 to 5.5). Relative mortality during the first 5 years of follow-up decreased significantly over time. Incident cases of 2002-2014 had 2.3 years shorter mean estimated life span than matched comparators. CONCLUSIONS Adult-onset and elderly-onset patients with UC, Crohn's disease and IBD-unclassified were all at increased risk of death. The increased mortality remained also after the introduction of biological therapies but has decreased over time.
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Affiliation(s)
- Ola Olén
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden.,Department of Clinical Science and Education Södersjukhuset, Karolinska Institutet, Stockholm, Sweden.,Sachs' Children and Youth Hospital, Stockholm South General Hospital, Stockholm, Sweden
| | - Johan Askling
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Michael C Sachs
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Martin Neovius
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Karin E Smedby
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Anders Ekbom
- Division of Clinical Epidemiology, Department of Medicine Solna, Karolinska Institutet, Stockholm, Sweden
| | - Jonas F Ludvigsson
- Department of Pediatrics, Örebro University Hospital, Örebro, Sweden.,Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.,Division of Epidemiology and Public Health, School of Medicine, University of Nottingham, Nottingham, UK.,Department of Medicine, Columbia University College of Physicians and Surgeons, New York, USA
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Altered microbial community structure in PI3Kγ knockout mice with colitis impeding relief of inflammation: Establishment of new indices for intestinal microbial disorder. Int Immunopharmacol 2019; 79:105901. [PMID: 31896510 DOI: 10.1016/j.intimp.2019.105901] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2019] [Revised: 08/22/2019] [Accepted: 09/07/2019] [Indexed: 12/19/2022]
Abstract
Lipopolysaccharide stimulates the intestinal microbiome to activate phosphoinositide 3 kinase (PI3K) signaling via several pathways; however, the direct effect that PI3K has on the intestinal bacterial community remains unclear. Herein, we investigate changes in the colonic microbiome of colitis PI3Kγ-knockout (PI3Kγ-/-) mice. Additionally, the effect of anal administration of colonic irrigation fluid from control mice to those with colitis was examined. Microbial 16S rRNA genes from the colonic mucosa of PI3Kγ-/- and WT mice were sequenced using Illumina MiSeq platform, and colonic IgA, IL-2, IL-10, and IL-17A production was quantified by western blot analysis. Myeloperoxidase (MPO) activity was detected by absorbance via colorimetric analysis. From the results, two new indices were derived by dividing the bacterial community into invading taxa, common taxa, and vanishing taxa. These indices were used to estimate the degree of microbiome disorder in chronic experimental colitis models. PI3Kγ-/- mice showed slower remission of inflammation as assessed by the disease activity index，pathological score, IL-2, IL-17, IL-10, IgA expression and MPO activity. The unique and common taxa of wild-type and PI3Kγ-/- mice increased as colitis symptoms regressed. Continuous loss of commensal bacteria happened with the continuous invasion of exogenous bacteria in the intestinal mucosa of PI3Kγ--/- mice after colitis begin to aggravate. However, transplantation of normal intestinal microbiota to PI3Kγ-/- mice promoted remission of inflammation; while the microbial dysbiosis observed during PI3Kγ dysfunction aggravated the intestinal microbiome disorder and impeded colitis recovery. Thus, the PI3Kγ signaling pathway may regulate microbial community composition in the colon.
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Tran V, Limketkai BN, Sauk JS. IBD in the Elderly: Management Challenges and Therapeutic Considerations. Curr Gastroenterol Rep 2019; 21:60. [PMID: 31776797 DOI: 10.1007/s11894-019-0720-7] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
PURPOSE OF REVIEW Elderly patients with inflammatory bowel disease (IBD) are increasing in prevalence as our population ages and the incidence of IBD increases. The purpose of this review is to describe the management challenges in elderly IBD patients, including comorbid conditions and therapeutic considerations unique to the elderly population. RECENT FINDINGS The elderly experience coexisting comorbidities that complicate IBD management. The disease course and potential side effects of treatments can impact the elderly IBD patient differently than younger IBD patients. The duration for colorectal cancer surveillance (CRC) also remains controversial and should be individualized to determine when discontinuation is appropriate. Given greater safety considerations in the elderly IBD population, treatment targets and management goals require a more personalized approach in the elderly, taking into account coexisting comorbidities, inflammatory burden, and functional limitations.
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Affiliation(s)
- Vivy Tran
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Berkeley N Limketkai
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
- UCLA Center for Inflammatory Bowel Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA
| | - Jenny S Sauk
- Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
- Vatche and Tamar Manoukian Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
- UCLA Center for Inflammatory Bowel Diseases, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, USA.
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Segal JP, Htet HMT, Limdi J, Hayee B. How to manage IBD in the 'elderly'. Frontline Gastroenterol 2019; 11:468-477. [PMID: 33101625 PMCID: PMC7569512 DOI: 10.1136/flgastro-2019-101218] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/09/2019] [Revised: 10/24/2019] [Accepted: 11/03/2019] [Indexed: 02/04/2023] Open
Abstract
As the incidence of inflammatory bowel disease (IBD) rises and the global population ages, the number of older people living with these conditions will inevitably increase. The challenges posed by comorbid conditions, polypharmacy, the unintended consequences of long-term treatment and the real but often underestimated mismatch between chronological and biological ages underpin management. Significantly, there may be differences in disease characteristics, presentation and management of an older patient with IBD, together with other unique challenges. Importantly, clinical trials often exclude older patients, so treatment decisions are frequently pragmatic, extrapolated from a number of sources of evidence and perhaps primarily dictated by concerns around adverse effects. This review aimed to discuss the epidemiology, clinical features and considerations with management in older patients with IBD.
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Affiliation(s)
| | | | - Jimmy Limdi
- Section of IBD, Division of Gastroenterology, The Pennine Acute Hospitals NHS Trust, Manchester, UK,Department of Gastroenterology, Manchester Academic Health Science Centre, Manchester, UK
| | - Bu'Hussain Hayee
- Department of Gastroenterology, King's College Hospital, London, UK
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Zhou Q, Shen ZF, Wu BS, Xu CB, He ZQ, Chen T, Shang HT, Xie CF, Huang SY, Chen YG, Chen HB, Han ST. Risk of Colorectal Cancer in Ulcerative Colitis Patients: A Systematic Review and Meta-Analysis. Gastroenterol Res Pract 2019; 2019:5363261. [PMID: 31781191 PMCID: PMC6874962 DOI: 10.1155/2019/5363261] [Citation(s) in RCA: 51] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2019] [Accepted: 08/22/2019] [Indexed: 02/07/2023] Open
Abstract
BACKGROUND Ulcerative colitis (UC) patients have an increased risk for the development of colorectal cancer (CRC). Our aim was to assess the risk of CRC in UC patients compared with disease extent, disease duration, and geographic variation. METHODS In this systematic review and meta-analysis, we searched PubMed, scientific meetings, and the bibliographies of identified articles, with English language restrictions for studies published from 1988 to 2018, and assessed the risk of CRC in UC patients. Patients with Crohn's disease, family history of CRC, and colorectal adenomatous polyp (CAP) were excluded from this research. The study was registered with PROSPERO, number CRD42018102213. FINDINGS We included 58 studies that included 267566 UC patients. Extensive UC and left-sided UC had a higher risk of CRC than proctitis UC. Geography also played a role in UC-associated CRC development. The time of malignant transformation in Asian UC patients started after 10-20 years of this disease duration. North American UC-associated CRC patients significantly increased in more than 30 years of this disease duration. CONCLUSION In a systematic review of the literature, we found that disease extent, disease duration, and geography were strong, independent risk factors in UC-associated CRC development.
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Affiliation(s)
- Qing Zhou
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Zhao-Feng Shen
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Ben-sheng Wu
- Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu, China
| | - Cheng-biao Xu
- Xuyi Hospital of Traditional Chinese Medicine, Huaian, Jiangsu, China
| | - Zhong-qi He
- Suzhou Hospital of Traditional Chinese Medicine, Suzhou, Jiangsu, China
| | - Tuo Chen
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Hong-tao Shang
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Chao-fan Xie
- Shishi General Hospital, Quanzhou, Fujian, China
| | - Si-yi Huang
- The First Affiliated Hospital of Guizhou University of Traditional Chinese Medicine, Guiyang, Guizhou, China
| | - Yu-gen Chen
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Hai-bo Chen
- Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
| | - Shu-tang Han
- Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China
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Viola A, Monterubbianesi R, Scalisi G, Furfaro F, Rea M, Saibeni S, Aratari A, Bringiotti R, Casella G, Cantoro L, Frankovic I, Calella F, Pugliese D, Orlando S, Samperi L, Cappello M, Mocci G, Manetti N, Annese V, Privitera AC, Inserra G, Caprioli F, D'Incà R, Principi M, Papi C, Castiglione F, Danese S, Ardizzone S, Bossa F, Kohn A, Manguso F, Alibrandi A, Fiorino G, Armuzzi A, Fries W. Late-onset Crohn's disease: a comparison of disease behaviour and therapy with younger adult patients: the Italian Group for the Study of Inflammatory Bowel Disease 'AGED' study. Eur J Gastroenterol Hepatol 2019; 31:1361-1369. [PMID: 31567640 DOI: 10.1097/meg.0000000000001546] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Disease phenotype and outcome of late-onset Crohn's disease are still poorly defined. METHODS In this Italian nationwide multicentre retrospective study, patients diagnosed ≥65 years (late-onset) were compared with young adult-onset with 16-39 years and adult-onset Crohn's disease 40-64 years. Data were collected for 3 years following diagnosis. RESULTS A total of 631 patients (late-onset 153, adult-onset 161, young adult-onset 317) were included. Colonic disease was more frequent in late-onset (P < 0005), stenosing behaviour was more frequent than in adult-onset (P < 0003), but fistulising disease was uncommon. Surgery rates were not different between the three age groups. Systemic steroids were prescribed more frequently in young adult-onset in the first year, but low bioavailability steroids were used more frequently in late-onset in the first 2 years after diagnosis (P < 0.036, P < 0.041, respectively). The use of immunomodulators and anti-TNF's even in patients with more complicated disease, that is, B2 or B3 behaviour (Montreal classification), remained significantly inferior (P < 0.0001) in late-onset compared to young adult-onset. Age at diagnosis, Charlson comorbidity index, and steroid used in the first year were negatively associated with the use of immunomodulators and biologics. Comorbidities, related medications and hospitalizations were more frequent in late-onset. Polypharmacy was present in 56% of elderly Crohn's disease patients. CONCLUSION Thirty-two percent of late-onset Crohn's disease presented with complicated disease behaviour. Despite a comparable use of steroids and surgery, immunomodulators and biologics were used in a small number of patients.
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Affiliation(s)
- Anna Viola
- Clinical Unit for Chronic Bowel Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina
| | - Rita Monterubbianesi
- Gastroenterology Operative Unit, Azienda Ospedaliera San Camillo-Forlanini, Department of Digestive Diseases, Campus Bio-Medico, University of Rome, Rome
| | - Giuseppe Scalisi
- Division of Gastroenterology, Department of Medical Sciences, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia
| | - Federica Furfaro
- Gastroenterology and Digestive Endoscopy, ASST Fatebenefratelli Sacco, Department of Biochemical and Clinical Sciences, University of Milan, Milan
| | - Matilde Rea
- Gastroenterology, Department of Clinical Medicine and Surgery, 'Federico II' University, Naples
| | - Simone Saibeni
- Gastroenterology Unit, Department of Internal Medicine, AO Guido Salvini, Ospedale di Rho, Milan
| | - Annalisa Aratari
- Gastroenterology Unit, Oncology Department, San Filippo Neri Hospital, Rome
| | - Roberto Bringiotti
- Gastroenterology Section (D.E.T.O.), Department of Emergency and Organ Transplantation, University of Bari, Bari
| | - Giovanni Casella
- Dipartimento di Medicina Ospedale Desio, Dipartimento di Medicina, Desio (MB)
| | - Laura Cantoro
- Gastroenterology Unit, Department of Surgery and Medicine, Campus BioMedico, University of Rome, Rome
| | - Iris Frankovic
- Gastroenterology Unit, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua
| | - Francesca Calella
- Gastroenterology, Ospedale San Giuseppe, Azienda USL11, Empoli, Firenze
| | - Daniela Pugliese
- IBD Unit, Presidio Columbus, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome
| | - Stefania Orlando
- Gastroenterology and Endoscopy Unit, Department of Internal Medicine, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan
| | - Leonardo Samperi
- Internal Medicine, Department of Medical and Pediatric Sciences, University of Catania, Catania
| | - Maria Cappello
- Sezione di Gastroenterologia e Epatologia, Dipartimento Biomedico di Medicina Interna e Specialistica (Di.Bi.M.I.S.), University of Palermo, Palermo
| | - Giammarco Mocci
- SC Gastroenterologia, Dipartimento di Chirurgia, Ospedale 'Brotzu', Cagliari
| | - Natalia Manetti
- Gastroenterology Unit, DEA-Medicina e Chirurgia Generale e d'Urgenza, University Hospital Careggi, Florence
| | - Vito Annese
- Gastroenterology Unit, DEA-Medicina e Chirurgia Generale e d'Urgenza, University Hospital Careggi, Florence
| | | | - Gaetano Inserra
- Internal Medicine, Department of Medical and Pediatric Sciences, University of Catania, Catania
| | - Flavio Caprioli
- Gastroenterology and Endoscopy Unit, Department of Internal Medicine, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Milan
- Department of Pathophysiology and Transplantation, University of Milan
| | - Renata D'Incà
- Gastroenterology Unit, Department of Surgical, Oncological, and Gastroenterological Sciences, University of Padua, Padua
| | - Mariabeatrice Principi
- Gastroenterology Section (D.E.T.O.), Department of Emergency and Organ Transplantation, University of Bari, Bari
| | - Claudio Papi
- Gastroenterology Unit, Oncology Department, San Filippo Neri Hospital, Rome
| | - Fabiana Castiglione
- Gastroenterology, Department of Clinical Medicine and Surgery, 'Federico II' University, Naples
| | - Silvio Danese
- IBD Center, Department of Gastroenterology, Humanitas Research Hospital
- Department of Biomedical Sciences, Humanitas University, Rozzano, Milan
| | - Sandro Ardizzone
- Gastroenterology and Digestive Endoscopy, ASST Fatebenefratelli Sacco, Department of Biochemical and Clinical Sciences, University of Milan, Milan
| | - Fabrizio Bossa
- Division of Gastroenterology, Department of Medical Sciences, IRCCS 'Casa Sollievo della Sofferenza', San Giovanni Rotondo, Foggia
| | - Anna Kohn
- Gastroenterology Operative Unit, Azienda Ospedaliera San Camillo-Forlanini, Department of Digestive Diseases, Campus Bio-Medico, University of Rome, Rome
| | - Francesco Manguso
- UOSC of Gastroenterology and Endoscopy, AORN 'A. Cardarelli', Naples
| | | | - Gionata Fiorino
- IBD Center, Department of Gastroenterology, Humanitas Research Hospital
| | - Alessandro Armuzzi
- IBD Unit, Presidio Columbus, Fondazione Policlinico Universitario A. Gemelli IRCCS, Università Cattolica del Sacro Cuore, Rome
| | - Walter Fries
- Clinical Unit for Chronic Bowel Disorders, Department of Clinical and Experimental Medicine, University of Messina, Messina
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LeBlanc JF, Wiseman D, Lakatos PL, Bessissow T. Elderly patients with inflammatory bowel disease: Updated review of the therapeutic landscape. World J Gastroenterol 2019; 25:4158-4171. [PMID: 31435170 PMCID: PMC6700701 DOI: 10.3748/wjg.v25.i30.4158] [Citation(s) in RCA: 25] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/19/2019] [Revised: 06/27/2019] [Accepted: 07/02/2019] [Indexed: 02/06/2023] Open
Abstract
High-quality data remains scarce in terms of optimal management strategies in the elderly inflammatory bowel disease (IBD) population. Indeed, available trials have been mostly retrospective, of small sample size, likely owing to under-representation of such a population in the major randomized controlled trials. However, in the last five years, there has been a steady increase in the number of published trials, helping clarify the estimated benefits and toxicity of the existing IBD armamentarium. In the Everhov trial, prescription strategies were recorded over an average follow-up of 4.2 years. A minority of elderly IBD patients (1%-3%) were treated with biologics within the five years following diagnosis, whilst almost a quarter of these patients were receiving corticosteroid therapy at year five of follow-up, despite its multiple toxicities. The low use of biologic agents in real-life settings likely stems from limited data suggesting lower efficacy and higher toxicity. This minireview will aim to highlight current outcome measurements as it portends the elderly IBD patient, as well as summarize the available therapeutic strategies in view of a growing body of evidence.
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Affiliation(s)
- Jean-Frédéric LeBlanc
- Department of Adult Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
| | - Daniel Wiseman
- Department of Medicine, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
| | - Peter L Lakatos
- Department of Adult Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
- 1st Department of Medicine, Semmelweis University, Budapest 1083, Hungary
| | - Talat Bessissow
- Department of Adult Gastroenterology, McGill University Health Centre, Montreal, QC H3G 1A4, Canada
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Kim D, Taleban S. A Comprehensive Review of the Diagnosis and Pharmacological Management of Crohn's Disease in the Elderly Population. Drugs Aging 2019; 36:607-624. [PMID: 31055789 DOI: 10.1007/s40266-019-00672-x] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
Abstract
Crohn's disease (CD) in the elderly is rising in prevalence, which is related to an increase in its incidence and improving life expectancies. There are differences in the presentation, natural history, and treatment of CD between adult-onset patients who progress to older age and patients who are initially diagnosed at an older age. Presentation at an older age may also delay or make diagnosis challenging due to accumulating co-morbidities that mimic inflammatory bowel disease. Differences exist between adult- and older-onset disease, yet many guidelines do not specifically distinguish the management of these two distinct populations. Identifying patients at high risk for progression or aggressive disease is particularly important as elderly patients may respond differently to medical and surgical treatment, and may be at higher risk for adverse effects. Despite newer agents being approved for CD, the data regarding efficacy and safety in the elderly are currently limited. Balancing symptom management with risks of medical and surgical therapy is an ongoing challenge and requires special consideration in these two distinct populations.
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Affiliation(s)
- David Kim
- Division of Gastroenterology and Hepatology, Banner University Medical Center, Tucson, AZ, USA.,Division of Gastroenterology and Hepatology, University of Arizona School of Medicine, Tucson, AZ, USA
| | - Sasha Taleban
- Division of Gastroenterology and Hepatology, University of Arizona School of Medicine, Tucson, AZ, USA. .,Arizona Center on Aging, University of Arizona, Tucson, AZ, USA.
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Sedano Muñoz R, Quera Pino R, Ibáñez Lazo P, Figueroa Corona C, Flores Pérez L. Aminosalicylates, thiopurines and methotrexate in inflammatory bowel disease: Is it possible to discontinue the treatment? GASTROENTEROLOGIA Y HEPATOLOGIA 2019; 42:339-347. [PMID: 30954317 DOI: 10.1016/j.gastrohep.2019.01.013] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/07/2018] [Revised: 01/15/2019] [Accepted: 01/16/2019] [Indexed: 06/09/2023]
Abstract
The current goals of treatment in inflammatory bowel disease, both Crohn's disease and ulcerative colitis, are to achieve clinical, endoscopic and ideally histological remission and improve the quality of life of these patients. Current therapies are effective in achieving remission in most cases, but there is a lack of clear guidelines on their optimal duration. This review aims to evaluate the current evidence on the withdrawal of therapy with 5-aminosalicylates, thiopurines and methotrexate. We also aim to identify which specific group of patients, while in remission and in the absence of risk factors, may be able to discontinue therapy without a significant risk of relapse.
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Affiliation(s)
- Rocío Sedano Muñoz
- Servicio de Gastroenterología, Hospital Clínico de la Universidad de Chile, Santiago, Chile
| | - Rodrigo Quera Pino
- Programa Enfermedad Inflamatoria Intestinal, Servicio de Gastroenterología, Clínica las Condes, Santiago, Chile.
| | - Patricio Ibáñez Lazo
- Programa Enfermedad Inflamatoria Intestinal, Servicio de Gastroenterología, Clínica las Condes, Santiago, Chile
| | - Carolina Figueroa Corona
- Programa Enfermedad Inflamatoria Intestinal, Servicio de Gastroenterología, Clínica las Condes, Santiago, Chile
| | - Lilian Flores Pérez
- Programa Enfermedad Inflamatoria Intestinal, Servicio de Gastroenterología, Clínica las Condes, Santiago, Chile
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Huguet JM, Iborra M, Bosca-Watts MM, Maroto N, Gil R, Cortes X, Hervás D, Paredes JM. Inflammatory bowel disease in patients over the age of 70 y. Does the disease duration influence its behavior? Scand J Gastroenterol 2018; 53:1079-1084. [PMID: 30189153 DOI: 10.1080/00365521.2018.1501603] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Revised: 06/14/2018] [Accepted: 07/12/2018] [Indexed: 02/04/2023]
Abstract
INTRODUCTION The fastest growing segment of our population is that of people above 70 years of age. Elderly patients with IBD exhibit several specific problems. Our objective was to evaluate the clinical course, the side effects of the treatments and the need for surgery of elderly patients, regardless of the age of onset. MATERIALS AND METHODS This was a cross-sectional study wherein retrospective data were collected from multiple centers from seven hospitals within the Valencia metropolitan area. Data were collected on patients older than 70 y with inflammatory bowel disease. RESULTS We identified a total of 331 patients older than 70 years of age (5.3% of patients monitored at our centers). The mean age at the time of the study was 77.34 y (±5.39). Mesalamine were the most frequently used medications. Corticosteroids were used in 66% of the patients. However, the use of corticosteroids and biologics was less probable in older patients (OR 0.96, p = .06). The longer the disease progressed, the more immunosuppressive medications were used (OR 1.3, p = .052). Neoplasms appeared in 41 patients (13%). Of the 36 patients with tumors that appeared after the onset of the disease, 20 patients had not been treated with immunomodulators or biologics. CONCLUSIONS Mesalamine was the most frequently used medication. There is no increased risk of tumors regarding the medications used. The use of immunosuppressive medications is more prevalent with longer disease progression times, although with a high rate of adverse events.
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Affiliation(s)
- Jose M Huguet
- a Digestive Disease Department , General University Hospital of Valencia , Valencia , Spain
| | - Marisa Iborra
- b Gastroenterology Department and CIBEREHD , Hospital Universitari i Politecnic La Fe , Valencia , Spain
| | - Marta Maia Bosca-Watts
- c Inflammatory Bowel Disease Unit, Digestive Disease Department , University of Valencia, University Clinic Hospital of Valencia , Valencia , Spain
| | - Nuria Maroto
- d Inflammatory Bowel Disease Unit, Digestive Disease Department , Hospital of Manises , Manises , Spain
| | - Rafael Gil
- e Digestive Disease Department , Arnau of Vilanova of Valencia Hospital , Spain Valencia
| | - Xavier Cortes
- f Digestive Disease Department , Hospital of Sagunto , Valencia , Spain
| | - David Hervás
- g Statistics Unit, Hospital Universitari i Politècnic la Fe , Valencia , Spain
| | - Jose M Paredes
- h Digestive Disease Department , Peset University Hospital of Valencia , Valencia , Spain
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Inflammatory Bowel Disease in the Baby to Baby Boomer: Pediatric and Elderly Onset of IBD. ACTA ACUST UNITED AC 2018; 16:289-305. [PMID: 30006766 DOI: 10.1007/s11938-018-0188-9] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
PURPOSE OF REVIEW Early- and late-onset of inflammatory bowel disease (IBD) may perhaps be etiologically distinct and potentially attributed to genetics, environmental or microbial factors. We review disease factors and clinical characteristics, as well as unique management and treatment strategies to consider when caring for the "baby" or "baby boomer" with IBD. RECENT FINDINGS Around 25% of cases of initial diagnosis of IBD is made before the age of 18 years old, and another 15-20% made after the age of 60. Crohn's disease (CD) typically presents as ileocolonic and stricturing or penetrating phenotype among early-onset, whereas among late-onset, it is mainly colonic and inflammatory. Pediatric ulcerative colitis (UC) is mostly pan-colonic versus primarily left-sided among the elderly. Treatment goal for both age groups is primarily symptom control, with growth and development also considered among pediatric patients. Due to alterations in pharmacokinetics, careful monitoring and reduced dose should be considered. A multidisciplinary care team is necessary to ensure better clinical outcomes. Onset of disease at either spectrum of age requires careful management and treatment, with both unique disease- and age-appropriate factors carefully considered.
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Lopez A, Pouillon L, Beaugerie L, Danese S, Peyrin-Biroulet L. Colorectal cancer prevention in patients with ulcerative colitis. Best Pract Res Clin Gastroenterol 2018; 32-33:103-109. [PMID: 30060933 DOI: 10.1016/j.bpg.2018.05.010] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/17/2018] [Accepted: 05/10/2018] [Indexed: 02/06/2023]
Abstract
Ulcerative colitis is characterized by chronic inflammation, which may lead to the accumulation of high levels of pro-inflammatory cytokines within the colonic mucosa, and thus to dysplastic lesions and cancer. Although the trend is decreasing, ulcerative colitis patients still have a 2.4 fold higher risk of colorectal cancer compared to the general population. The key task is to control colonic inflammation, and a rapid step-up approach while closely monitoring intestinal inflammation are recommented. Surveillance colonoscopy program demonstrated its efficacy for reducing the incidence of colorectal cancer in ulcerative colitis. The impact of medication on the reduction of colorectal cancer risk was hardly investigated and it remains unclear whether they have intrinsic anti-neoplastic properties or only downregulate inflammatory pathways. Several studies showed a decreased risk of colorectal cancer in ulcerative colitis patients treated with 5-aminosalicylic acid and chemoprevention with mesalamine compounds is currently recommended. The current level of evidence is too low for thiopurines and anti-TNFα agents. Large, prospective cohort studies are ongoing and are likely to bring new findings about the impact of drugs on colorectal cancer risk in the current era of biologics.
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Affiliation(s)
- Anthony Lopez
- Department of Gastroenterology and NGERE Unit, Inserm, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France.
| | - Lieven Pouillon
- Department of Gastroenterology and NGERE Unit, Inserm, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France; Imelda GI Clinical Research Centre, Imeldaziekenhuis Bonheiden, Imeldalaan, Bonheiden, Belgium
| | - Laurent Beaugerie
- Department of Gastroenterology, AP-HP, Hôpital Saint-Antoine, F-75012, France; ERL 1057 INSERM/UMRS 7203, UPMC University, Paris, 06F-75005, Paris, France
| | - Silvio Danese
- Department of Biomedical Sciences, Humanitas University, Milan, Italy; IBD Center, Humanitas Clinical and Research Center, Milan, Italy
| | - Laurent Peyrin-Biroulet
- Department of Gastroenterology and NGERE Unit, Inserm, University Hospital of Nancy, Lorraine University, Vandoeuvre-lès-Nancy, France
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Kedia S, Limdi JK, Ahuja V. Management of inflammatory bowel disease in older persons: evolving paradigms. Intest Res 2018; 16:194-208. [PMID: 29743832 PMCID: PMC5934592 DOI: 10.5217/ir.2018.16.2.194] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/05/2017] [Revised: 11/11/2017] [Accepted: 11/14/2017] [Indexed: 02/06/2023] Open
Abstract
The incidence and prevalence of inflammatory bowel disease (IBD) is increasing, and considering the aging population, this number is set to increase further in the future. The clinical features and natural history of elderly-onset IBD have many similarities with those of IBD in younger patients, but with significant differences including a broader differential diagnosis. The relative lack of data specific to elderly patients with IBD, often stemming from their typical exclusion from clinical trials, has made clinical decision-making somewhat challenging. Treatment decisions in elderly patients with IBD must take into account age-specific concerns such as comorbidities, locomotor and cognitive function, and polypharmacy, to set realistic treatment targets in order to enable personalized treatment and minimize harm. Notwithstanding paucity of clinical data, recent studies have provided valuable insights, which, taken together with information gleaned from previous studies, can broaden our understanding of IBD. These insights may contribute to the development of paradigms for the holistic and, when possible, evidence-based management of this potentially vulnerable population and are the focus of this review.
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Affiliation(s)
- Saurabh Kedia
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
| | - Jimmy K Limdi
- Salford & Pennine Clinical Research Unit, The Pennine Acute Hospitals NHS Trust, Manchester, UK
| | - Vineet Ahuja
- Department of Gastroenterology and Human Nutrition, All India Institute of Medical Sciences, New Delhi, India
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