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1
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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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Zamani M, Alizadeh-Tabari S, Murad MH, Singh S, Ananthakrishnan AN, Malekzadeh R, Talley NJ. Meta-analysis: Risk of lymphoma in patients with inflammatory bowel disease in population-based cohort studies. Aliment Pharmacol Ther 2024; 60:1264-1275. [PMID: 39310939 DOI: 10.1111/apt.18277] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/02/2024] [Revised: 07/22/2024] [Accepted: 09/02/2024] [Indexed: 10/25/2024]
Abstract
BACKGROUND There are inconsistencies in the results of the studies investigating the association between inflammatory bowel disease (IBD) and lymphoma. AIMS The aim of this study is to systematically appraise the risk of lymphoma development in patients with IBD. METHODS We searched Embase, PubMed and Scopus from inception to 30 April 2024 to identify population-based cohort studies that evaluated the risk of lymphoma in patients with IBD in comparison with those without IBD. We carried out random-effects meta-analyses and estimated pooled relative risks (RRs) with 95% confidence intervals (CIs). RESULTS We identified 23 eligible studies reporting 2078 lymphoma events in 656,731 patients with IBD. Patients with IBD had 30% higher odds of lymphoma (RR = 1.30 [95% CI: 1.21-1.40]). The risk of developing both Hodgkin's lymphoma (nine studies, RR = 1.29 [95% CI: 1.06-1.53]) and non-Hodgkin's lymphoma (16 studies, RR = 1.31 [95% CI: 1.20-1.42]) was increased in patients with IBD (p for interaction = 0.881). The increased risk of lymphoma was observed in both Crohn's disease (17 studies, RR = 1.54 [95% CI: 1.27-1.80]) and ulcerative colitis (20 studies, RR = 1.22 [95% CI: 1.09-1.35]) (p for interaction = 0.026). Meta-regression demonstrated that mean age of patients, study year, mean study follow-up duration, and percentages of immunomodulators and biologics use did not influence study outcome. CONCLUSIONS The risk of lymphoma is only modestly increased in patients with IBD, with Crohn's disease having a slightly higher risk than ulcerative colitis. In IBD, there appears to be no difference between the risks of Hodgkin's and non-Hodgkin's lymphoma.
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Affiliation(s)
- Mohammad Zamani
- Digestive Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Shaghayegh Alizadeh-Tabari
- Digestive Diseases Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mohammad Hassan Murad
- Kern Center for the Science of Healthcare Delivery Research, Mayo Clinic, Rochester, Minnesota, USA
| | - Siddharth Singh
- Division of Gastroenterology, and Division of Biomedical Informatics, University of California san Diego, La Jolla, California, USA
| | - Ashwin N Ananthakrishnan
- Division of Gastroenterology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA
| | - Reza Malekzadeh
- Digestive Oncology Research Center, Digestive Diseases Research Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Nicholas J Talley
- School of Medicine and Public Health, University of Newcastle, Newcastle, New South Wales, Australia
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Garcia JL, Rosa I, da Silva JP, Moleiro J, Claro I. Incidence and risk factors for neoplasia in inflammatory bowel disease. Asia Pac J Clin Oncol 2024; 20:559-564. [PMID: 36915954 DOI: 10.1111/ajco.13908] [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: 04/28/2022] [Revised: 10/22/2022] [Accepted: 11/24/2022] [Indexed: 03/15/2023]
Abstract
INTRODUCTION Inflammatory Bowel Disease (IBD) patients may have an increased risk of neoplasia. The aim was to evaluate the incidence of malignant neoplasia in IBD patients, associated risk factors and therapy adjustments. METHODS Unicentric retrospective cohort study. All patients followed for IBD in a tertiary portuguese hospital and oncological centre during 2015-2020 were included. RESULTS 318 patients were included female 55.0%, age at diagnosis = 37.24(±15,28), Crohn's disease 52.5%, Primary Sclerosing Cholangitis n = 7, family history of cancer n = 12, previous diagnosis of neoplasia n = 23(7.2%). 42 cancers were diagnosed in 35 patients (11.0%) - median of 12.0(IQR = 7.5-21.0) years after IBD diagnosis. Most affected organs were the skin (n = 15 in 11 patients; melanoma = 1), colon/rectum (n = 8 in 6 patients), prostate (n = 4), breast (n = 3) and anal canal (n = 2). In those with non-melanoma skin cancer, 6 were under active treatment with azathioprine and 2 had stopped it for more than two years. In the univariate analysis, the occurrence of neoplasia was positively associated with tobacco exposure (p = 0.022), age at IBD diagnosis (p = 0.021), and negatively with infliximab exposure (p = 0.046). In 9 cases, cancer treatment was different because of the IBD, while IBD treatment was changed in 9 patients. In those affected by cancer, in the univariate analysis, its cure/remission was negatively associated with tobacco exposure (p = 0.004) and positively with salicylates use (p = 0.007). CONCLUSION In IBD patients, cancer mostly affected the skin and the lower digestive system. As in the general population, tobacco exposure was a risk factor for the development of neoplasia.
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Affiliation(s)
- Joana Lemos Garcia
- Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal
| | - Isadora Rosa
- Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal
| | | | - Joana Moleiro
- Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal
| | - Isabel Claro
- Instituto Português de Oncologia de Lisboa Francisco Gentil, Lisboa, Portugal
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Zhou X, Zhang Q, Wang D, Xiang Z, Ruan J, Tang L. Risk of Hematologic Malignancies in Patients with Inflammatory Bowel Disease: A Meta-Analysis of Cohort Studies. Gut Liver 2024; 18:845-856. [PMID: 38953119 PMCID: PMC11391147 DOI: 10.5009/gnl240119] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/21/2024] [Revised: 04/08/2024] [Accepted: 04/22/2024] [Indexed: 07/03/2024] Open
Abstract
Background/Aims Inflammatory bowel disease (IBD) may contribute to the development of hematologic malignancies. In this study, the potential relationship between IBD and hematologic malignancies was investigated. Methods We searched the PubMed, Web of Science, Embase, and Cochrane Library databases for all cohort studies comparing the incidence of hematologic malignancies in non-IBD populations with that in IBD patients, and we extracted relevant data from January 2000 to June 2023 for meta-analysis. Results Twenty cohort studies involving 756,377 participants were included in this study. The results showed that compared with the non-IBD cohort, the incidence of hematologic malignancies in the IBD cohort was higher (standardized incidence ratio [SIR]=3.05, p<0.001). According to the specific types of IBD, compared with the non-IBD patients, the incidences of hematologic malignancies in ulcerative colitis patients (SIR=2.29, p=0.05) and Crohn's disease patients (SIR=3.56, p=0.005) were all higher. In the subgroup analysis of hematologic malignancy types, compared with the control group, the incidences of non-Hodgkin's lymphoma (SIR=1.70, p=0.01), Hodgkin's lymphoma (SIR=3.47, p=0.002), and leukemia (SIR=3.69, p<0.001) were all higher in the IBD cohort. Conclusions The incidence of hematologic malignancies, including non-Hodgkin's lymphoma, Hodgkin's lymphoma, and leukemia is higher in patients with IBD (ulcerative colitis or Crohn's disease) than in non-IBD patients.
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Affiliation(s)
- Xiaoshuai Zhou
- Department of Anus and Intestine Surgery, Ningbo Yinzhou No. 2 Hospital, Ningbo, China
| | - Qiufeng Zhang
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Dongying Wang
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Zhiyi Xiang
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Jiale Ruan
- The First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, China
| | - Linlin Tang
- Department of Gastroenterology, Zhuji People's Hospital, Shaoxing, China
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Schabl L, Connelly TM, de Camargo MGM, Sancheti H, Steele SR, Kessler H. Crohn's disease-related versus sporadic colorectal cancer: A stage-matched case-control study based on four decades of experience. J Surg Oncol 2024; 130:644-652. [PMID: 39004924 DOI: 10.1002/jso.27768] [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: 04/23/2024] [Revised: 05/31/2024] [Accepted: 07/01/2024] [Indexed: 07/16/2024]
Abstract
BACKGROUND AND OBJECTIVES This study compares surgical and oncological outcomes in patients with Crohn's disease (CD)-related colorectal cancer (CRC) to those with sporadic CRC. METHODS Patients treated between 1983 and 2013 were matched by stage, age, gender, American Society of Anesthesiologists (ASA), cancer site, and adjuvant chemotherapy. RESULTS For stages I and II, 107 patients were matched (58.9% male, mean age 59 years, 59.8% with ASA score 3). Tumor sites included the right (17.7%), transverse (4.7%), left colon (15.9%), and rectum (61.7%). CD patients exhibited longer operative times, higher pT stages, and 2.60 times the odds of postoperative complications (p = 0.03). Overall and disease-free survival were similar. For stage III, 54 patients were matched (57.4% male, mean age 54 years, 46.3% with ASA score 3). The cancer site distribution was right (29.7%), transverse (3.7%), left colon (18.5%), and rectum (48.1%). CD patients had longer operative times, increased blood loss, more involved lymph nodes, higher pT- and pN-stages. The rates of postoperative complications were not different (p = 0.19). CD-related CRC patients had similar overall (p = 0.06), and local recurrence-free survival (p = 0.07). CONCLUSIONS Despite facing worse perioperative and pathological characteristics, survival differences in stages I-III CD-related CRC compared with sporadic CRC patients were not significantly different.
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Affiliation(s)
- Lukas Schabl
- Department for Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Tara M Connelly
- Department for Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | | | - Himani Sancheti
- Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, Ohio, USA
| | - Scott R Steele
- Department for Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
| | - Hermann Kessler
- Department for Colorectal Surgery, Digestive Disease Institute, Cleveland Clinic, Cleveland, Ohio, USA
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Guo Z, Xu C, Fang Z, Yu X, Yang K, Liu C, Ning X, Dong Z, Liu C. Inflammatory bowel disease and breast cancer: A two-sample bidirectional Mendelian randomization study. Medicine (Baltimore) 2024; 103:e38392. [PMID: 38847661 PMCID: PMC11155618 DOI: 10.1097/md.0000000000038392] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/21/2024] [Accepted: 05/08/2024] [Indexed: 06/10/2024] Open
Abstract
There is a correlation between IBD and breast cancer according to previous observational studies. However, so far there is no evidence to support if there is a causal relationship between these 2 diseases. We acquired comprehensive Genome-Wide Association Study (GWAS) summary data on IBD (including ulcerative colitis [UC] and Crohn disease [CD]) as well as breast cancer of completely European descent from the IEU GWAS database. The estimation of bidirectional causality between IBD (including UC and CD) and breast cancer was achieved through the utilization of 2-sample Mendelian randomization (MR). The MR results were also assessed for any potential bias caused by heterogeneity and pleiotropy through sensitivity analyses. Our study found a bidirectional causal effect between IBD and breast cancer. Genetic susceptibility to IBD was associated with an increased risk of breast cancer (OR = 1.053, 95% CI: 1.016-1.090, P = .004). Similarly, the presence of breast cancer may increase the risk of IBD (OR = 1.111, 95% CI: 1.035-1.194, P = .004). Moreover, the bidirectional causal effect between IBD and breast cancer can be confirmed by another GWAS of IBD. Subtype analysis showed that CD was associated with breast cancer (OR = 1.050, 95% CI: 1.020-1.080, P < .001), but not UC and breast cancer. There was a suggestive association between breast cancer and UC (OR = 1.106, 95% CI: 1.011-1.209, P = .028), but not with CD. This study supports a bidirectional causal effect between IBD and breast cancer. There appear to be considerable differences in the specific associations of UC and CD with AD. Understanding that IBD including its specific subtypes and breast cancer constitute common risk factors can contribute to the clinical management of both diseases.
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Affiliation(s)
- Zihao Guo
- Department of General Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Changyu Xu
- Department of Ultrasound, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhihao Fang
- Department of General Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xiaoxiao Yu
- Department of General Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Kai Yang
- Department of General Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Changxu Liu
- Department of General Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Xinwei Ning
- Department of General Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Zhichao Dong
- Department of General Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
| | - Chang Liu
- Department of General Surgery, Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
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Stasik K, Filip R. The Complex Relationship between Mechanisms Underlying Inflammatory Bowel Disease, Its Treatment, and the Risk of Lymphomas: A Comprehensive Review. Int J Mol Sci 2024; 25:4241. [PMID: 38673824 PMCID: PMC11049907 DOI: 10.3390/ijms25084241] [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: 02/25/2024] [Revised: 04/06/2024] [Accepted: 04/08/2024] [Indexed: 04/28/2024] Open
Abstract
Patients with inflammatory bowel disease may be at higher risk of developing lymphomas and other cancers of the gastrointestinal tract. In addition, there may be a link between the use of thiopurines or anti-tumor necrosis factor drugs (anti-TNF) and these pathologies. The treatment of patients with Crohn's disease who have previously been diagnosed with lymphoma is a challenge for gastroenterologists. In this report, we examine important clinical issues related to the treatment of patients with inflammatory bowel disease with active lymphoma, as well as of patients with hematological cancer history. In this discussion, we take into account most of the available treatments for inflammatory bowel disease, as well as the impact of chronic inflammation and viral infections. In addition, we try to find common ground for the development of lymphoproliferative disorders and autoimmune diseases. Patients with inflammatory bowel disease may be at higher risk of developing lymphomas and other cancers of the gastrointestinal tract. Chronic inflammatory processes and viral infections play an important role in carcinogenesis. In addition, there may be a link between the use of thiopurines or anti-TNF drugs and these pathologies. A significant risk of the development of lymphoma in people undergoing each therapy should be considered, and it should be estimated how much greater this risk will be in patients with a history of lymphoproliferative disorders. The following review is an attempt to answer which therapy would be the most appropriate for patients with Crohn's disease and a history of lymphoma treatment. A lack of clear guidelines creates great challenges for doctors.
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Affiliation(s)
- Katarzyna Stasik
- Department of Gastroenterology with IBD Unit, Clinical Hospital No. 2, 35-301 Rzeszow, Poland;
| | - Rafał Filip
- Faculty of Medicine, University of Rzeszow, 35-959 Rzeszow, Poland
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Yu C, Xu J, Xu S, Tang L, Han Q, Zeng X, Huang Y, Yu T, Sun Z. Exploring genetic associations of Crohn's disease and ulcerative colitis with extraintestinal cancers in European and East Asian populations. Front Immunol 2024; 15:1339207. [PMID: 38404590 PMCID: PMC10885353 DOI: 10.3389/fimmu.2024.1339207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/15/2023] [Accepted: 01/19/2024] [Indexed: 02/27/2024] Open
Abstract
Background Previous studies have reported associations of Crohn's disease (CD) and ulcerative colitis (UC) with the risks of extraintestinal cancers, but the causality remains unclear. Methods Using genetic variations robustly associated with CD and UC extracted from genome-wide association studies (GWAS) as instrumental variables. Nine types of extraintestinal cancers of European and Asian populations were selected as outcomes. We used the inverse variance weighted method as the primary approach for two-sample Mendelian randomization analysis. Sensitivity analyses were carried out to evaluate the reliability of our findings. Results In the European population, we found that CD showed a potential causal relationship with pancreatic cancer (OR: 1.1042; 95% CI: 1.0087-1.2088; P=0.0318). Meanwhile, both CD (outliers excluded: OR: 1.0208; 95% CI: 1.0079-1.0339; P=0.0015) and UC (outliers excluded: OR: 1.0220; 95% CI: 1.0051-1.0393; P=0.0108) were associated with a slight increase in breast cancer risk. Additionally, UC exhibited a potential causal effect on cervical cancer (outliers excluded: OR: 1.1091; 95% CI: 1.0286-1.1960; P=0.0071). In the East Asian population, CD had significant causal effects on pancreatic cancer (OR: 1.1876; 95% CI: 1.0741-1.3132; P=0.0008) and breast cancer (outliers excluded: OR: 0.9452; 95% CI: 0.9096-0.9822; P=0.0040). For UC, it exhibited significant causal associations with gastric cancer (OR: 1.1240; 95% CI: 1.0624-1.1891; P=4.7359×10-5), bile duct cancer (OR: 1.3107; 95% CI: 1.0983-1.5641; P=0.0027), hepatocellular carcinoma (OR: 1.2365; 95% CI: 1.1235-1.3608; P=1.4007×10-5) and cervical cancer (OR: 1.3941; 95% CI: 1.1708-1.6599; P=0.0002), as well as a potential causal effect on lung cancer (outliers excluded: OR: 1.1313; 95% CI: 1.0280-1.2449; P=0.0116). Conclusions Our study provided evidence that genetically predicted CD may be a risk factor for pancreatic and breast cancers in the European population, and for pancreatic cancer in the East Asian population. Regarding UC, it may be a risk factor for cervical and breast cancers in Europeans, and for gastric, bile duct, hepatocellular, lung, and cervical cancers in East Asians. Therefore, patients with CD and UC need to emphasize screening and prevention of site-specific extraintestinal cancers.
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Affiliation(s)
- Chengdong Yu
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Jiawei Xu
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Siyi Xu
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Lei Tang
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Qinyuan Han
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Xiaoqiang Zeng
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Yanxiao Huang
- Jiangxi Medical College, Nanchang University, Nanchang, China
| | - Tenghua Yu
- Department of breast surgery, Jiangxi Cancer Hospital, Nanchang, China
| | - Zhengkui Sun
- Department of breast surgery, Jiangxi Cancer Hospital, Nanchang, China
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Yokota Y, Imai T, Kawahara M, Inatomi O, Nishida A, Kakuta Y, Masamune A, Andoh A. Thiopurines exert harmful effects on spermatogenesis in Nudt15 R138C knock-in mice. J Gastroenterol 2024; 59:109-118. [PMID: 38097780 DOI: 10.1007/s00535-023-02059-7] [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: 09/26/2023] [Accepted: 11/07/2023] [Indexed: 01/26/2024]
Abstract
BACKGROUND The association between thiopurine use and testicular reproductive functions remains unclear. In this study, we investigated whether thiopurines affect testicular functions based on the NUDT15 genotypes using Nudt15R138C knock-in mice. METHODS The male Nudt15R138C knock-in mice (9-12 weeks) were treated with mercaptopurine (MP: 0.5 mg/kg/day) for 4 or 12 weeks. To examine reversibility, some mice were maintained for a further 12 weeks under MP-free condition. RESULTS After MP treatment for 4 weeks, Nudt15R138C/R138C mice exhibited a significant reduction of testis weight compared to Nudt15+/+ mice and Nudt15+/R138C mice. The epithelial height and diameter of seminiferous tubules were significantly reduced in Nudt15R138C/R138C mice compared to Nudt15+/+ and Nudt15+/R138C mice. Apoptotic cells were significantly increased in Nudt15R138C/R138C mice, and most of apoptotic cells were spermatogonia. There were no significant changes in sperm counts and sperm morphology in MP-treated Nudt15R138C/R138C mice after 4-week MP treatment. On the other hand, after MP treatment for 12 weeks, the Nudt15+/R138C mice, but not Nudt15+/+ mice, exhibited a significant reduction in the testis weight and atrophic changes of seminiferous tubules, but these changes disappeared after 12-week rearing under MP-free condition. Despite a significant increase in abnormal sperm rate, there were no changes in the ability to conceive. No differences in serum levels of follicle-stimulating hormone or testosterone were observed between MP-treated Nudt15+/R138C and Nudt15+/+ mice after 12-week MP treatment. CONCLUSIONS Thiopurines exert harmful effects on testicular reproductive function according to host NUDT15 genotypes.
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Affiliation(s)
- Yoshihiro Yokota
- Department of Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan
| | - Takayuki Imai
- Department of Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan
| | - Masahiro Kawahara
- Department of Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan
| | - Osamu Inatomi
- Department of Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan
| | - Atsushi Nishida
- Department of Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan
| | - Yoichi Kakuta
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8575, Japan
| | - Atsushi Masamune
- Division of Gastroenterology, Tohoku University Graduate School of Medicine, Sendai, Miyagi, 980-8575, Japan
| | - Akira Andoh
- Department of Medicine, Shiga University of Medical Science, Seta-Tsukinowa, Otsu, Shiga, 520-2192, Japan.
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Zhang H, Hu C, Zhang Z, Li P, Shen G, Sun J. Two-sample Mendelian randomization study reveals no causal relationship between inflammatory bowel disease and urological cancers. Front Genet 2023; 14:1275247. [PMID: 38188502 PMCID: PMC10771298 DOI: 10.3389/fgene.2023.1275247] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/09/2023] [Accepted: 12/06/2023] [Indexed: 01/09/2024] Open
Abstract
Background: The relationship between inflammatory bowel disease (IBD) and urological cancers has been identified in epidemiological and observational studies, while the causality remains uncertain. We examined whether IBD is causally associated with urological cancers in a Mendelian randomization (MR) study. Methods: The causal relationship between IBD, its main subtypes, and urological cancers was investigated using genome-wide association study data. To obtain more reliable conclusions, all outcomes were divided into training and validation sets. Eligible single-nucleotide polymorphisms were selected as instrumental variables based on MR analysis assumptions. The inverse variance-weighted (IVW) method was employed as the main method along with four other complementary methods. Results: In this two-sample MR study, no genetic evidence for the causal effect of IBD on urological cancers was found in either the training or validation sets using the IVW method. Similarly, we did not observe any significant association between Crohn's disease or ulcerative colitis and urological cancers. The results of the other methods are in accordance with those obtained using the IVW method. Conclusion: In this study, we confirmed that IBD is not a causal genetic risk factor for urological cancer in a European population.
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Affiliation(s)
- Haoyang Zhang
- Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Can Hu
- Department of Urology, Suzhou Xiangcheng People’s Hospital, Suzhou, China
| | - Zhiyu Zhang
- Department of Urology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, China
| | - Peng Li
- Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Gang Shen
- Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
| | - Jiale Sun
- Department of Urology, Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu, China
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Patel RK, Frankel L, Cardeiro M, Hansen W, Takabe K, Rashid OM. The Role of Crohn Disease on Breast Cancer Incidence: A Clinical Analysis. World J Oncol 2023; 14:457-463. [PMID: 38022407 PMCID: PMC10681792 DOI: 10.14740/wjon1644] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/28/2023] [Accepted: 08/26/2023] [Indexed: 12/01/2023] Open
Abstract
Background Crohn disease is a chronic inflammatory disease that can affect the entire gastrointestinal tract. The pathophysiology of this disease characteristically involves transmural inflammation, which predisposes patients to various gastrointestinal cancers such as colon cancer. Although the increased risk of gastrointestinal cancers in Crohn disease has been well established, the risk of extra-gastrointestinal cancers remains unknown. We sought to study the risk of breast cancer in patients with Crohn disease. Methods The data for this retrospective study were compiled using the International Classification of Disease Ninth Revision (ICD-9) and ICD 10th Revision (ICD-10) codes from the national Health Insurance Portability and Accountability Act (HIPAA)-compliant PearlDiver database from 2010 to 2019. Patients were matched for age, sex, and Charlson Comorbidity Index (CCI). Statistical analyses were implemented to assess Chi-squared, logistic regression, and odds ratio. Results The database query resulted in 70,027 patients in both the control and Crohn disease groups. The incidence of breast cancer was 4,087 in the control group compared to 654 in the Crohn disease group. The P value was < 2.2 × 10-16 and the odds ratio was 0.15 (95% confidence interval (CI)). Patients without Crohn disease had an increased prevalence of breast cancer throughout all age ranges compared to patients with Crohn disease. Additionally, patients without Crohn disease had higher rates of breast cancer throughout the four major regions of the United States. In terms of healthcare costs, patients with breast cancer and a history of Crohn disease paid $23.87 more per hospital visit compared to patients with breast cancer and no history of Crohn disease. Conclusions The results of this study indicate a statistically significant correlation between Crohn disease and a reduced incidence of breast cancer. This finding is true across all age groups and across the United States. Further study is required to investigate a possible mechanism between the pathophysiology of Crohn disease ultimately leading to reduced tumorigenesis in the breast.
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Affiliation(s)
- Raina K. Patel
- Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, FL, USA
| | - Lexi Frankel
- Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, FL, USA
| | - Matthew Cardeiro
- Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, FL, USA
| | - Wade Hansen
- Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, FL, USA
| | - Kazuaki Takabe
- Department of Surgical Oncology, Roswell Park Comprehensive Cancer Center, Buffalo, NY, USA
- Department of Surgery, University at Buffalo Jacobs School of Medicine and Biomedical Sciences, The State University of New York, Buffalo, NY, USA
| | - Omar M. Rashid
- Nova Southeastern University Dr. Kiran C. Patel College of Allopathic Medicine, Fort Lauderdale, FL, USA
- Michael and Dianne Bienes Comprehensive Cancer Center, Holy Cross Health, Fort Lauderdale, FL, USA
- University of Miami Leonard M. School of Medicine, Miami, FL, USA
- Massachusetts General Hospital, Boston, MA, USA
- Broward Health, Fort Lauderdale, FL, USA
- Topline MD Alliance, FL, USA
- Memorial Health, Pembroke Pines, FL, USA
- Delray Medical Center, Delray, FL, USA
- Complex General Surgical Oncology, General and Robotic Surgery, TopLine MD Alliance, Fort Lauderdale, FL 33308, USA
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12
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Follin-Arbelet B, Cvancarova Småstuen M, Hovde Ø, Jelsness-Jørgensen LP, Moum B. Risk of Cancer in Patients With Crohn's Disease 30 Years After Diagnosis (the IBSEN Study). CROHN'S & COLITIS 360 2023; 5:otad057. [PMID: 37886706 PMCID: PMC10599393 DOI: 10.1093/crocol/otad057] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/14/2023] [Indexed: 10/28/2023] Open
Abstract
Background Patients with Crohn's disease (CD) are most often diagnosed as young adults; therefore, long-term studies are needed to assess the risk of cancer over their lifetime. Thus, the aims of the present study were to determine the risk of cancer in a Norwegian population-based cohort (the Inflammatory Bowel South Eastern Norway [IBSEN] study), 30 years after diagnosis, and to assess whether patients with CD were at an increased risk of specific cancer types. Methods The IBSEN cohort prospectively included all incident patients diagnosed between 1990 and 1993. Data on cancer incidence were obtained from the Cancer Registry of Norway. Overall and cancer-specific hazard ratios (HRs) for CD patients compared with age- and sex-matched controls were modeled using Cox regression. Standardized incidence ratios (SIRs) were estimated compared to the general population. Results In total, the cohort included 237 patients with CD, and 36 of them were diagnosed with cancer. Compared to the general Norwegian population, patients with CD had an increased overall risk of cancer (HR = 1.56, 95% CI: 1.06-2.28), particularly male patients (HR = 1.85, 95% CI: 1.08-3.16). The incidence of lung cancer and nonmelanoma skin cancer was increased; however, the difference was not statistically significant (SIR = 2.29, 95% CI: 0.92-4.27 and SIR = 2.45, 95% CI: 0.67-5.37, respectively). Conclusions After 30 years of follow-up, the risk of all cancers in patients with CD was increased compared to the general population.
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Affiliation(s)
- Benoit Follin-Arbelet
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Gastroenterology, Oslo University Hospital, Oslo, Norway
- Østfold University College, Halden, Norway
| | - Milada Cvancarova Småstuen
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Department of Public Health Oslo Metropolitan University, Oslo, Norway
| | - Øistein Hovde
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Innlandet Hospital Trust, Gjøvik, Norway
| | | | - Bjørn Moum
- Institute of Clinical Medicine, University of Oslo, Oslo, Norway
- Østfold Hospital Trust, Sarpsborg, Norway
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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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14
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Cheng W, Liao Y, Mou R, Xiao X, Jia Y. Inflammatory bowel disease and prostate cancer risk: a two-sample Mendelian randomization analysis. Front Immunol 2023; 14:1157313. [PMID: 37409117 PMCID: PMC10318899 DOI: 10.3389/fimmu.2023.1157313] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/02/2023] [Accepted: 06/07/2023] [Indexed: 07/07/2023] Open
Abstract
Background Previous epidemiological observational studies have reported an association between inflammatory bowel disease (IBD) and prostate cancer (PCa), but the causality is inconclusive. The purpose of this study was to evaluate the causality of IBD on PCa using the mendelian randomization (MR) analysis. Methods We performed a two-sample MR analysis with public genome-wide association studies (GWAS) data. Eligible instrumental variables (IVs) were selected according to the three assumptions of MR analysis. The inverse-variance weighted (IVW) method was the main method. Complementary methods included the MR-Egger regression, the Weighted Median, the Simple Mode, the Weighted Mode and MR pleiotropy residual sum and outlier (MR-PRESSO) methods. Results Genetically determined IBD did not have a causal effect on PCa (IVW P > 0.05). Additionally, there was no causal effect of Crohn's disease (CD) and ulcerative colitis (UC) on PCa in the MR analysis (IVW P > 0.05). Results of complementary methods were consistent with those of the IVW method. Conclusions This study does not support a causal association of IBD on PCa, which is in contrast to most observational studies.
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Affiliation(s)
- Wen Cheng
- Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Yang Liao
- Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Ruiyu Mou
- Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Xian Xiao
- Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
| | - Yingjie Jia
- Department of Oncology, First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin, China
- National Clinical Research Center for Chinese Medicine Acupuncture and Moxibustion, Tianjin, China
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15
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Zhou BG, Yu Q, Jiang X, Mei YZ, Ding YB, Wang M. Association between inflammatory bowel disease and risk of incident prostate cancer: a systematic review and meta-analysis of cohort studies. Int J Colorectal Dis 2023; 38:168. [PMID: 37310514 DOI: 10.1007/s00384-023-04465-y] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 06/07/2023] [Indexed: 06/14/2023]
Abstract
BACKGROUND AND OBJECTIVE Numerous observational studies have been conducted to investigate the potential association between inflammatory bowel disease (IBD) and prostate cancer (PCa). However, a definitive conclusion has yet to be established. We therefore performed a meta-analysis to explore the relationship between these two conditions. METHODS PubMed, Embase, and Web of Science databases were systematically searched to identify all relevant cohort studies that investigated the association between IBD and risk of incident PCa published from inception to February 2023. The pooled hazard ratios (HRs) with 95% confidence intervals (CI) was calculated as effect size for the outcome based on random-effects model meta-analysis. RESULTS A total of 18 cohort studies with 592,853 participants were included. The meta-analysis revealed that IBD was linked to an elevated risk of incident PCa (HR = 1.20, 95% CI: 1.06-1.37, P = 0.004). Further subgroup analyses revealed that ulcerative colitis (UC) was linked to an increased risk of incident PCa (HR = 1.20, 95% CI: 1.06-1.38, P = 0.006), while Crohn's disease (CD) is not significantly associated with a higher risk of PCa (HR = 1.03, 95% CI: 0.91-1.17, P = 0.65). There was a significant correlation between IBD and an elevated risk of incident PCa in the European population, but such a correlation was not observed in the Asian and North American populations. Sensitivity analyses indicated that our results were robust. CONCLUSIONS Our latest evidence indicates that IBD was linked to an elevated risk of incident PCa, especially in UC patients and the European population.
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Affiliation(s)
- Ben-Gang Zhou
- Dalian Medical University, Dalian, Liaoning Province, China
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368, Hanjiang Middle Road, Hanjiang District, Yangzhou, Jiangsu Province, China
| | - Qi Yu
- Department of Gastroenterology, Wuxi Xinwu District Xinrui Hospital, Wuxi, Jiangsu Province, China
| | - Xin Jiang
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368, Hanjiang Middle Road, Hanjiang District, Yangzhou, Jiangsu Province, China
| | - Yu-Zhou Mei
- Department of Gastroenterology, The People's Hospital of China Three Gorges University, Yichang, Hubei Province, China
| | - Yan-Bing Ding
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368, Hanjiang Middle Road, Hanjiang District, Yangzhou, Jiangsu Province, China.
| | - Mei Wang
- Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368, Hanjiang Middle Road, Hanjiang District, Yangzhou, Jiangsu Province, China.
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16
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Burisch J. Long-term disease course, cost and prognosis of inflammatory bowel disease: epidemiological studies of a European and a Danish inception cohort. APMIS 2023; 131 Suppl 147:1-46. [PMID: 37336790 DOI: 10.1111/apm.13334] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 06/21/2023]
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17
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Russo MF, Diddoro A, Iodice A, Severi C, Castagneto-Gissey L, Casella G. Incidence of lymphomas in inflammatory bowel disease: report of an emblematic case, systematic review, and meta-analysis. Front Med (Lausanne) 2023; 10:1172634. [PMID: 37206474 PMCID: PMC10188968 DOI: 10.3389/fmed.2023.1172634] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2023] [Accepted: 04/14/2023] [Indexed: 05/21/2023] Open
Abstract
Introduction Over the past 20 years, the increasing use of combined therapy with immunosuppressants and biologic agents has markedly reduced the use of steroids in the management of inflammatory bowel diseases (IBD). However, medical therapy seems to promote, in the long run, carcinogenesis resulting in an increased risk of developing different types of malignancies, including lymphomas. The aim of this study was to systematically review the current incidence and prognosis of lymphoid neoplasms occurring in patients with IBD. Methods Studies analyzing the incidence of lymphomas in subjects of age >18 years affected by IBD were included in this systematic review and meta-analysis. Studies focusing on pediatric populations, not reporting person-years of follow-up, or with a duration < 1 year were excluded. PubMed, Embase, Web of Science Core Collection, and Cochrane Central Register were searched from inception through January 2022. Publication bias within studies was assessed using Begg's and Egger's tests and random effects model. Quantitative results were synthesized using relative-risk meta-analysis. PRISMA guidelines were used to carry out this systematic review (PROSPERO Registration Number: CRD42023398348). Results A total of 345 studies published between 1985 and 2022, with a total of 6,17,386 patients were included in the meta-analysis. Substantial heterogeneity between studies prevented the pooling of estimates (I2 = 97.19%). Evidence of publication bias was overall low (p = 0.1941). Patients affected by Crohn's disease (CD) were 1,86,074 (30.13%), while 2,78,876 (46.17%) were diagnosed with UC. The remaining 23.7% of cases were diagnosed with indeterminate colitis. Immunomodulators and biologic therapy were used in 24,520 (5.27%), and 17,972 (3.86%) patients, respectively. Reported incidence rates for lymphoma in IBD ranged from 0.0/100,000 person/years (py) (95% CI 0.0-3.7/100,000) to 89/100,000 py (95% CI 36-160/100,000). Reported incidence rates of lymphoma in CD ranged from 0.0/100,000 py (95% CI 0.0-3.7/100,000) to 91/100,000 py (95% CI 18-164/100,000). For UC, the incidence rate ranged from 0.0/100,000 py (95% CI 0.0-3.7/100,000) to 95/100,000 py (95% CI 0-226/100,000). Male-to-female ratio was ~4:1. Therapy with immunomodulators was directly associated with an increased incidence of lymphoma (p < 0.0001). Evidence of publication bias was overall low (p = 0 .1941). Conclusions The evidence arising from this study highlights a correlation between the use of immunomodulators and subsequent lymphoma development. Combined multidisciplinary approach and long-term follow-up are warranted in order to decrease mortality deriving from the coexistence of both conditions. Systematic review registration Identifier: CRD42023398348.
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Affiliation(s)
| | | | | | - Carola Severi
- Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy
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18
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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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19
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Ding NS, Tassone D, Al Bakir I, Wu K, Thompson AJ, Connell WR, Malietzis G, Lung P, Singh S, Choi CHR, Gabe S, Jenkins JT, Hart A. Systematic Review: The Impact and Importance of Body Composition in Inflammatory Bowel Disease. J Crohns Colitis 2022; 16:1475-1492. [PMID: 35325076 PMCID: PMC9455788 DOI: 10.1093/ecco-jcc/jjac041] [Citation(s) in RCA: 21] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/11/2021] [Revised: 02/06/2022] [Accepted: 03/10/2022] [Indexed: 12/31/2022]
Abstract
BACKGROUND AND AIMS Alterations in body composition are common in inflammatory bowel disease [IBD] and have been associated with differences in patient outcomes. We sought to consolidate knowledge on the impact and importance of body composition in IBD. METHODS We performed a systematic search of MEDLINE, EMBASE and conference proceedings by combining two key research themes: inflammatory bowel disease and body composition. RESULTS Fifty-five studies were included in this review. Thirty-one focused on the impact of IBD on body composition with a total of 2279 patients with a mean age 38.4 years. Of these, 1071 [47%] were male. In total, 1470 [64.5%] patients had Crohn's disease and 809 [35.5%] had ulcerative colitis. Notably, fat mass and fat-free mass were reduced, and higher rates of sarcopaenia were observed in those with active IBD compared with those in clinical remission and healthy controls. Twenty-four additional studies focused on the impact of derangements in body composition on IBD outcomes. Alterations in body composition in IBD are associated with poorer prognoses including higher rates of surgical intervention, post-operative complications and reduced muscle strength. In addition, higher rates of early treatment failure and primary non-response are seen in patients with myopaenia. CONCLUSIONS Patients with IBD have alterations in body composition parameters in active disease and clinical remission. The impacts of body composition on disease outcome and therapy are broad and require further investigation. The augmentation of body composition parameters in the clinical setting has the potential to improve IBD outcomes in the future.
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Affiliation(s)
- Nik Sheng Ding
- Inflammatory Bowel Disease Unit, St Mark’s Hospital, Harrow, UK
- Gastroenterology Department, St Vincent’s Hospital, Melbourne, Australia
| | - Daniel Tassone
- Gastroenterology Department, St Vincent’s Hospital, Melbourne, Australia
| | | | - Kyle Wu
- Gastroenterology Department, St Vincent’s Hospital, Melbourne, Australia
| | | | - William R Connell
- Gastroenterology Department, St Vincent’s Hospital, Melbourne, Australia
| | | | - Phillip Lung
- Inflammatory Bowel Disease Unit, St Mark’s Hospital, Harrow, UK
| | - Siddharth Singh
- Division of Gastroenterology and Division of Biomedical Informatics, University of California San Diego, La Jolla, California, USA
| | | | - Simon Gabe
- Inflammatory Bowel Disease Unit, St Mark’s Hospital, Harrow, UK
| | - John T Jenkins
- Department of Surgery and Cancer, Imperial College, London, UK
| | - Ailsa Hart
- Inflammatory Bowel Disease Unit, St Mark’s Hospital, Harrow, UK
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20
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Burisch J. The Impact of Anti-tumour Necrosis Factor Alpha Agents on the Risk of Colorectal Cancer. J Crohns Colitis 2022; 16:871-872. [PMID: 35834841 DOI: 10.1093/ecco-jcc/jjab198] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Affiliation(s)
- Johan Burisch
- Gastrounit, Hvidovre Hospital, University of Copenhagen, Hvidovre, Denmark.,Copenhagen Center for Inflammatory Bowel Disease in Children, Adolescents and Adults, Hvidovre Hospital, Hvidovre, Denmark
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21
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Burisch J, Lophaven S, Munkholm P, Langholz E. Surgery, cancer and mortality among patients with ulcerative colitis diagnosed 1962-1987 and followed until 2017 in a Danish population-based inception cohort. Aliment Pharmacol Ther 2022; 55:339-349. [PMID: 34713926 DOI: 10.1111/apt.16677] [Citation(s) in RCA: 13] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/31/2021] [Revised: 07/20/2021] [Accepted: 10/15/2021] [Indexed: 12/12/2022]
Abstract
BACKGROUND Long-term data on the natural disease course of unselected patients with ulcerative colitis (UC) are limited. AIMS To determine the long-term course and prognosis of UC, including patients' risks of surgery, cancer and mortality, in a population-based cohort followed for over 50 years METHODS: All incident patients with UC diagnosed between 1962 and 1987 in Copenhagen County, Denmark were included in a population-based cohort. We extracted information about IBD-related surgeries, cancers and mortality from patient files from 1962 to 1987, and from the Danish National Patient Registry, Cancer Registry, and Register of Causes of Death during 1988-2017. Patients were matched with up to 50 individuals from the general population. RESULTS We followed 1161 patients for a median of 34 years (range: 0.1-56.0). Median age at diagnosis was 33 years (range: 2-88). The cumulative probability of colectomy 10, 20, 30, 40 and 50 years after diagnosis was 22% (95% CI: 20%-25%), 27% (95% CI: 25%-30%), 31% (95% CI: 28%-34%), 34% (95% CI: 31%-37%), and 40% (95% CI: 36%-44%), respectively. The risk of small intestinal, colon, rectal and anal cancer was higher than among controls, as was cancer of the skin, pancreas and thyroid. All-cause mortality was lower than controls (adjusted RR: 0.90, 95% CI: 0.82-0.99). CONCLUSION In this population-based cohort of UC patients diagnosed between 1962 and 1987, 40% underwent colectomy within 50 years of diagnosis. Physicians need to be aware that UC patients are at increased risk of intestinal and extra-intestinal cancers. However, UC patients' risk of mortality is comparable to that of the background population.
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Affiliation(s)
- Johan Burisch
- Department of Gastroenterology, North Zealand Hospital, University of Copenhagen, Hillerød, Denmark
| | | | - Pia Munkholm
- Department of Gastroenterology, North Zealand Hospital, University of Copenhagen, Hillerød, Denmark
| | - Ebbe Langholz
- Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Herlev, Denmark.,Institute for Clinical Medicine, University of Copenhagen, Copenhagen, Denmark
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22
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Zhang H, Zhang M, Chen X, Guo M, Zhou R, Lv H, Li Y, Tan B, Li J, Xu H, Zheng W, Yang H, Qian J. Risk of malignancy in patients with inflammatory bowel disease: a population-based cohort study from China. Int J Cancer 2022; 150:1770-1778. [PMID: 35037241 DOI: 10.1002/ijc.33932] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/13/2021] [Revised: 12/15/2021] [Accepted: 12/22/2021] [Indexed: 11/11/2022]
Abstract
Carcinogenesis is one of major complications for patients with inflammatory bowel disease (IBD) and causes poor prognosis. We aimed to describe cancer incidence in Chinese IBD cohort compared with general population-based cancer registration data and further explore associated risk factors for cancer occurrence in IBD patients. IBD inpatients from January 1998 to January 2018 were included in this study. Patients were followed up from date of IBD diagnosis until either the date of first cancer diagnosis or January 2019. Standardized incidence ratios (SIRs) of overall cancer and site-specific cancers were calculated. A total of 869 UC and 516 CD patients were finally included with median follow-up time of 7 and 5 years respectively. 53 cases developed malignancies. After standardization by age and gender, standardized incidence ratio (SIR) of total cancer occurrence in IBD patients was 1.77 (95%CI, 1.33-2.32). As for UC, digestive cancers (SIR 3.75; 95%CI, 2.29-5.80), thyroid cancer (SIR 10.34; 95%CI, 4.72-19.64) and hematological malignancies (SIR 6.25; 95%CI, 1.68-16.00) had the highest incidence, which were prominent in young and middle-aged patients. Use of steroids, immunosuppressants or infliximab did not present higher risk of malignancies in UC patients. There were no significant difference in cancer risk between CD patients and general population. In conclusion, the increased risks of multiple cancers are particularly prominent in Chinese UC patients and these findings can provide more targeted guidance for cancer monitoring in Chinese IBD patients.
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Affiliation(s)
- Huimin Zhang
- 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
| | - Xuanfu Chen
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Mingyue Guo
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Runing Zhou
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hong Lv
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Yue Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Bei Tan
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Ji Li
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Hui Xu
- Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
| | - Weiyang Zheng
- 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
| | - 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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23
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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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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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25
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Caviglia GP, Martini G, Armandi A, Rosso C, Vernero M, Bugianesi E, Astegiano M, Saracco GM, Ribaldone DG. Risk Factors of Urothelial Cancer in Inflammatory Bowel Disease. J Clin Med 2021; 10:3257. [PMID: 34362041 PMCID: PMC8347965 DOI: 10.3390/jcm10153257] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/03/2021] [Revised: 07/22/2021] [Accepted: 07/22/2021] [Indexed: 01/31/2023] Open
Abstract
Extraintestinal cancers are important complications in patients with inflammatory bowel disease (IBD). A limited number of publications are available regarding the association between IBD and urothelial cancer. The primary outcome of our study was the comparison of the prevalence of urothelial cancer in patients with IBD with respect to the prevalence in the general population. Secondary outcomes were the assessment of risk factors for the onset of urothelial cancer in IBD. In a retrospective study we examined the medical records of all patients with a confirmed diagnosis of IBD followed in our clinic between 1978 and 2021. For each of the patients with identified urothelial cancer, more than ten patients without cancer were analyzed. Furthermore, 5739 patients with IBD were analyzed and 24 patients diagnosed with urothelial cancer were identified. The incidence of urothelial cancer, compared with the incidence in the general population, was not significantly different (0.42% vs. 0.42%; p = 0.98). Twenty-three cases were then compared (1 case was discarded due to lack of follow-up data) against 250 controls. During the multivariate analysis, smoking (odds ratio, OR = 8.15; 95% confidence interval, CI = 1.76-37.63; p = 0.007) and male sex (OR = 4.04; 95% CI = 1.29-12.66; p = 0.016) were found as risk factors. In conclusion, patients with IBD have a similar risk of developing urothelial cancer compared to the general population, but males with a history of smoking are at increased risk.
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Affiliation(s)
- Gian Paolo Caviglia
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Giorgio Martini
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Angelo Armandi
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Chiara Rosso
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Marta Vernero
- Department of Internal Medicine, San Matteo Hospital, 27100 Pavia, Italy;
| | - Elisabetta Bugianesi
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Marco Astegiano
- Department of General and Specialist Medicine, Gastroenterologia-U, Città della Salute e della Scienza di Torino, C.so Bramante 88, 10126 Turin, Italy;
| | - Giorgio Maria Saracco
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
| | - Davide Giuseppe Ribaldone
- Department of Medical Sciences, Division of Gastroenterology, University of Torino, 10126 Torino, Italy; (G.P.C.); (G.M.); (C.R.); (E.B.); (G.M.S.)
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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: 61] [Impact Index Per Article: 15.3] [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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Geng Z, Geng Q. Risk of Urinary Bladder Cancer in Patients With Inflammatory Bowel Diseases: A Meta-Analysis. Front Surg 2021; 8:636791. [PMID: 34124132 PMCID: PMC8188732 DOI: 10.3389/fsurg.2021.636791] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/02/2020] [Accepted: 03/26/2021] [Indexed: 12/24/2022] Open
Abstract
A systematic search of the PubMed, Cochrane, Embase, and Web of Science databases was conducted to investigate the risk of urinary bladder cancer (BC) in patients with inflammatory bowel disease (IBD). We identified 168 articles, of which 11 met the inclusion and exclusion criteria. Our analysis included 165,176 patients with IBD, 491 of whom had BC. Overall, the pooled standardized incidence ratio (SIR) was 0.99 (95% CI: 0.87–1.12; I2 = 0%). Further subgroup analysis showed that BC risk was neither statistically higher for Crohn's disease (CD) (SIR: 1.19; 95% CI: 0.94–1.44; I2 = 0%) nor for patients with ulcerative colitis (UC) (SIR: 0.92; 95% CI: 0.77–1.06; I2 = 0%). In the analysis of two case-control studies providing data on BC in UC and CD combined, IBD patients seemed to have a higher risk of BC than non-IBD patients (relative risk: 1.25; 95% CI: 0.77–2.03; I2 = 37.5%). Although the overall risk of BC was not significantly increased among patients with IBD, there was a weak trend for the risk to be elevated in CD patients, indicating marginal significance. These findings may primarily be explained by the opposite effects of smoking on CD and UC as well as the immunosuppressive drugs these patients often take.
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Affiliation(s)
- Zhihua Geng
- Department of Orthopedics of Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
| | - Qing Geng
- Department of Thoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China
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Abstract
BACKGROUND Anal lesions in cases of Crohn's disease can give rise to adenocarcinoma of the anal canal; however, the oncologic outcomes in these patients have not yet been thoroughly investigated. OBJECTIVE This study aimed to clarify the influence of Crohn's disease on the oncologic outcomes in patients with adenocarcinoma of the anal canal. DESIGN This was a retrospective observational study from a prospectively collected database. SETTINGS The study was conducted at a single institution. PATIENTS This study included 102 patients with adenocarcinoma of the anal canal, including 34 (33.3%) with Crohn's disease-associated lesions and 68 (66.7%) with non-Crohn's disease-associated lesions. MAIN OUTCOME MEASURES Prognostic factors were detected using a Cox regression analysis, and the oncologic outcomes were calculated using the Kaplan-Meier method. RESULTS Crohn's disease-associated patients were significantly younger (45 vs 62 y; p < 0.001), had a high incidence of external/anal gland-type disease (61.8% vs 5.9%, p < 0.001) and had large tumors (7.1 ± 3.0 vs 4.7 ± 2.3 cm; p = 0.03) in comparison with non-Crohn's disease-associated patients. A Cox regression analysis showed that an advanced clinical T stage (T3 or T4; tumor size ≥5 cm) was an independent risk factor for 5-year local recurrence-free survival (HR = 3.49; p = 0.04), disease-free survival (HR = 2.82; p = 0.008), and overall survival (HR = 2.92; p = 0.006), and Crohn's disease association was an independent prognostic factor for local recurrence-free survival (HR = 2.29; p = 0.04) and overall survival (HR = 2.86; p = 0.04). The oncologic outcomes of patients who had the 2 abovementioned negative factors (cT3,4 Crohn's disease-associated patients) were significantly poorer than those of T3,4 non-Crohn's disease-associated patients (5-year local recurrence-free survival: 32.5% vs 70.4%, p = 0.001; disease-free survival: 15.9% vs 40.7%, p = 0.04; overall survival: 25.8% vs 71.0%, p = 0.007). LIMITATIONS This was a single-arm, retrospective study. CONCLUSIONS Significantly poorer oncologic outcomes were confirmed in Crohn's disease-associated patients with large tumors. Thus, it is important to perform careful surveillance of anal lesions in patients with Crohn's disease while taking these facts into consideration. See Video Abstract at http://links.lww.com/DCR/B449. RESULTADOS ONCOLGICOS ADVERSOS DEL ADENOCARCINOMA DEL CANAL ANAL EN PACIENTES CON ENFERMEDAD DE CROHN ANTECEDENTES:Las lesiones anales en casos de enfermedad de Crohn pueden dar lugar a un adenocarcinoma del canal anal; sin embargo, los resultados oncológicos en estos pacientes aún no se han investigado a fondo.OBJETIVOS:Este estudio tuvo como objetivo aclarar la influencia de la enfermedad de Crohn en los resultados oncológicos en pacientes con adenocarcinoma del canal anal.DISEÑO:Estudio observacional retrospectivo de una base de datos recopilada prospectivamente.ENTORNO CLINICO:El estudio se realizó en una sola institución.PACIENTES:Este estudio incluyó 102 pacientes con adenocarcinoma del canal anal, incluidos 34 (33,3%) con lesiones asociadas a la enfermedad de Crohn y 68 (66,7%) con lesiones no asociadas a la enfermedad de Crohn.PRINCIPALES MEDIDAS DE VOLARACION:Los factores pronósticos se detectaron mediante un análisis de regresión de Cox y los resultados oncológicos se calcularon utilizando el método de Kaplan-Meier.RESULTADOS:Los pacientes asociados a la enfermedad de Crohn eran significativamente más jóvenes (45 versus a 62 años, p <0,001), tenían una alta incidencia de enfermedad de tipo glandular externo/ anal (61,8% versus a 5,9%, p <0,001) y tumores grandes (7,1 ± 3,0 cm versus a 4,7 ± 2,3 cm, p = 0,03) en comparación con los pacientes no asociados a la enfermedad de Crohn. Un análisis de regresión de Cox mostró que un estadío clínico T avanzado (T3,4; tamaño del tumor ≥5 cm) era un factor de riesgo independiente para la supervivencia sin recidiva local (SLF) a 5 años (índice de riesgo [HR]: 3,49, p = 0,04), supervivencia libre de enfermedad (SSE) (HR: 2,82, p = 0,008) y supervivencia general (SG) (HR: 2,92, p = 0,006), y la enfermedad de Crohn asociada fue un factor pronóstico independiente para la SLF (HR: 2,29, p = 0,04) y SG (HR: 2,86, p = 0,04). Los resultados oncológicos de los pacientes que tenían los dos factores negativos mencionados anteriormente (pacientes asociados con la enfermedad de Crohn cT3,4) fueron significativamente peores que los de los pacientes no asociados con la enfermedad de Crohn con T3,4 (LFS a 5 años: 32,5% versus a 70,4 %, p = 0,001; SSE: 15,9% versus a 40,7%, p = 0,04; SG: 25,8% versus a 71,0%, p = 0,007).LIMITACIONES:Un estudio retrospectivo de un solo brazo.CONCLUSIONES:Se confirmaron resultados oncológicos significativamente peores en pacientes asociados con la enfermedad de Crohn con tumores grandes. Por lo tanto, es importante realizar una vigilancia cuidadosa de las lesiones anales en pacientes con enfermedad de Crohn. Consulte Video Resumen en http://links.lww.com/DCR/B449.
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Cutaneous Manifestations in Biological-Treated Inflammatory Bowel Disease Patients: A Narrative Review. J Clin Med 2021; 10:jcm10051040. [PMID: 33802483 PMCID: PMC7959457 DOI: 10.3390/jcm10051040] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/07/2021] [Revised: 02/12/2021] [Accepted: 02/24/2021] [Indexed: 12/13/2022] Open
Abstract
The biologic era has greatly improved the treatment of Crohn’s disease and ulcerative colitis. Biologics can however induce a wide variety of skin eruptions, especially those targeting the TNF-α and Th17 pathway. These include infusion reactions, eczema, psoriasis, lupus, alopecia areata, vitiligo, lichenoid reactions, granulomatous disorders, vasculitis, skin cancer, and cutaneous infections. It is important to recognize these conditions as treatment-induced adverse reactions and adapt the treatment strategy accordingly. Some conditions can be treated topically while others require cessation or switch of the biological therapy. TNF-α antagonists have the highest rate adverse skin eruptions followed by ustekinumab and anti-integrin receptor blockers. In this review, we provide an overview of the most common skin eruptions which can be encountered in clinical practice when treating IBD (Inflammatory bowel disease) patients and propose a therapeutic approach for each condition.
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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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Squamous Cell Carcinoma of the Hand: A Retrospective Study in Immunosuppressed and Immunocompetent Individuals. Dermatol Surg 2021; 46:1014-1020. [PMID: 32028479 DOI: 10.1097/dss.0000000000002336] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
BACKGROUND Cutaneous squamous cell carcinoma (SCC) of the hand presents a treatment challenge because of the anatomical complexity of this location. Immunosuppressed patients are disproportionately affected by cutaneous SCC. Existing data on SCC of the hand are primarily presented in the orthopedic literature, and may thus be affected by referral bias. OBJECTIVE Characterization of epidemiology and treatment outcomes for hand versus nonhand cutaneous SCC in immunosuppressed versus immunocompetent patients, across all clinical departments. MATERIALS AND METHODS Single-institution retrospective cohort study of cutaneous SCC evaluated over 3 years and hand SCC over an additional 5 years. RESULTS A cohort of 522 hand SCC cases (1,746 total SCC) was ascertained among 1,064 patients, of whom 175 were immunosuppressed. Occurrence on the hand was more common for SCC arising in immunosuppressed versus immunocompetent patients (38% vs 24% of cases respectively). Hand SCC cases demonstrated balanced laterality and comparable spectra of differentiation regardless of immunosuppression. No cases of hand SCC metastasis were observed over greater than 2 years' mean follow-up, and digital amputation was only required in approximately 1% of hand SCCs. CONCLUSION In our cohort, assessment of hand SCC across all clinical departments suggests more favorable prognosis than reflected in the previous literature.
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Zhang C, Liu S, Peng L, Wu J, Zeng X, Lu Y, Shen H, Luo D. Does inflammatory bowel disease increase the risk of lower urinary tract tumors: a meta-analysis. Transl Androl Urol 2021; 10:164-173. [PMID: 33532306 PMCID: PMC7844520 DOI: 10.21037/tau-20-1020] [Citation(s) in RCA: 13] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/05/2023] Open
Abstract
Background Inflammatory bowel disease, including ulcerative colitis and Crohn’s disease, is characterized by chronic inflammation that could be a risk factor for extraintestinal cancer. The aim of this study is to evaluate whether inflammatory bowel disease is related to the risk of lower urinary tract tumors. Methods A systematical research was performed on various medical databases including PubMed, the Cochrane Library, Embase and Web of Science from inception to April 2020. Data were independently extracted by two reviewers. The Newcastle-Ottawa Scale and the Oxford Centre for Evidence-Based Medicine criteria were used to assess the quality of included articles. The analysis was completed by STATA version 14.2. Results Six hundred and twelve of records were initially identified and 16 studies were included in the final analysis. In general, inflammatory bowel disease patients were not at increased risk of prostate cancer, bladder cancer and male genital cancer. In the subgroup analysis, Crohn’s disease patients seemed to have borderline increased risk of prostate cancer [standardized incidence ratio: 1.05; 95% confidence interval (CI): 0.90–1.21; I2=15.1%] and bladder cancer (standardized incidence ratio: 1.19; 95% CI: 0.94–1.44; I2=0.0%), and ulcerative colitis patients seemed to have borderline increased risk of prostate cancer (standardized incidence ratio: 1.13; 95% CI: 0.93–1.33; I2=73.5%). Conclusions Inflammatory bowel disease did not significantly increase the risk of prostate cancer, bladder cancer and male genital cancer. Crohn’s disease patients seemed to have a higher risk of prostate cancer and bladder cancer, and ulcerative colitis patients seemed to have a higher risk of prostate cancer. ulcerative colitis patients in East Asian countries have significantly increased prostate cancer risk.
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Affiliation(s)
- Chi Zhang
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Shengzhuo Liu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Liao Peng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Jiapei Wu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Xiao Zeng
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Yiping Lu
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Hong Shen
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
| | - Deyi Luo
- Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, China
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Meyers TJ, Weiner AB, Graff RE, Desai AS, Cooley LF, Catalona WJ, Hanauer SB, Wu JD, Schaeffer EM, Abdulkadir SA, Kundu SD, Witte JS. Association between inflammatory bowel disease and prostate cancer: A large-scale, prospective, population-based study. Int J Cancer 2020; 147:2735-2742. [PMID: 32399975 DOI: 10.1002/ijc.33048] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/11/2020] [Revised: 04/14/2020] [Accepted: 04/28/2020] [Indexed: 12/24/2022]
Abstract
Inflammatory bowel disease (IBD) is an established risk factor for colorectal cancer. Recent reports suggesting IBD is also a risk factor for prostate cancer (PC) require further investigation. We studied 218 084 men in the population-based UK Biobank cohort, aged 40 to 69 at study entry between 2006 and 2010, with follow-up through mid-2015. We assessed the association between IBD and subsequent PC using multivariable Cox regression analyses, adjusting for age at assessment, ethnic group, UK region, smoking status, alcohol drinking frequency, body mass index, Townsend Deprivation Index, family history of PC and previous prostate-specific antigen testing. Mean age at study entry was 56 years, 94% of the men were white, and 1.1% (n = 2311) had a diagnosis of IBD. After a median follow-up of 78 months, men with IBD had an increased risk of PC (adjusted hazard ratio [aHR] = 1.31, 95% confidence interval [CI] = 1.03-1.67, P = .029). The association with PC was only among men with the ulcerative colitis (UC; aHR = 1.47, 95% CI = 1.11-1.95, P = .0070), and not Crohn's disease (aHR 1.06, 95% CI = 0.63-1.80, P = .82). Results are limited by lack of data on frequency of health care interactions. In a large-scale, prospective cohort study, we detected an association between IBD, and UC specifically, with incident PC diagnosis.
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Affiliation(s)
- Travis J Meyers
- Department of Epidemiology and Biostatistics, University of California San Francisco (UCSF), San Francisco, California, USA
| | - Adam B Weiner
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Rebecca E Graff
- Department of Epidemiology and Biostatistics, University of California San Francisco (UCSF), San Francisco, California, USA
| | - Anuj S Desai
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Lauren Folgosa Cooley
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - William J Catalona
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Stephen B Hanauer
- Department of Medicine, Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Jennifer D Wu
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Edward M Schaeffer
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Sarki A Abdulkadir
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - Shilajit D Kundu
- Department of Urology, Northwestern University Feinberg School of Medicine, Chicago, Illinois, USA
| | - John S Witte
- Department of Epidemiology and Biostatistics, University of California San Francisco (UCSF), San Francisco, California, USA
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Daugherty TT, Swerlick RA. Clinical context for cancer risk of immunosuppressive agents used in dermatology. Dermatol Ther 2020; 34:e14433. [PMID: 33084077 DOI: 10.1111/dth.14433] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2020] [Revised: 09/24/2020] [Accepted: 10/14/2020] [Indexed: 11/27/2022]
Abstract
Dermatologic care of inflammatory skin conditions has been transformed over recent decades through the use of small molecules disease-modifying anti-rheumatic drugs and targeted biologic therapies. Alongside the tremendous benefit of these agents, concerns remain regarding possible side effects, particularly cancer risk. To improve guidance and counseling of patients with skin diseases who are considering treatment with such agents, this article reviews available information on the risk of malignancies in patients treated with these agents. When possible, this article adds clinical context to risk through a number needed to harm that estimates the number of patients a provider would need to treat with a given agent in 1 year to cause a single adverse outcome over time.
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Affiliation(s)
| | - Robert Andrew Swerlick
- Alicia Leizman Stonecipher Chair of Dermatology, Department of Dermatology, Emory University School of Medicine, Atlanta, Georgia, USA
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Dahmus J, Rosario M, Clarke K. Risk of Lymphoma Associated with Anti-TNF Therapy in Patients with Inflammatory Bowel Disease: Implications for Therapy. Clin Exp Gastroenterol 2020; 13:339-350. [PMID: 32982364 PMCID: PMC7501969 DOI: 10.2147/ceg.s237646] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/09/2020] [Accepted: 09/08/2020] [Indexed: 12/27/2022] Open
Abstract
Anti-tumor necrosis factor alpha (ATA) therapy plays a significant role in the treatment of moderate to severe inflammatory bowel disease (IBD). There are concerns regarding risks associated with their use, including malignancy and, specifically, lymphoma. Many previous studies have sought to determine whether there is a true link between ATA therapy in IBD and development of lymphoma. However they have been hindered by short follow-up times, few cases, and confounding factors such as previous thiopurine exposure. This review seeks to update the literature by evaluating more recent studies assessing the link between ATA monotherapy and lymphoma development. It also summarizes findings of those studies and provides additional clinical guidance pertaining to this class of biologic therapy. ![]()
Point your SmartPhone at the code above. If you have a QR code reader the video abstract will appear. Or use: https://youtu.be/CWKgDs6bdFg
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Affiliation(s)
- Jessica Dahmus
- Gastroenterology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Michelle Rosario
- Gastroenterology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
| | - Kofi Clarke
- Gastroenterology, Penn State Milton S. Hershey Medical Center, Hershey, PA, USA
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Wintjens D, Bergey F, Saccenti E, Jeuring S, van den Heuvel T, Romberg-Camps M, Oostenbrug L, Masclee A, Martins dos Santos V, Jonkers D, Pierik M. Disease Activity Patterns of Crohn's Disease in the First Ten Years After Diagnosis in the Population-based IBD South Limburg Cohort. J Crohns Colitis 2020; 15:391-400. [PMID: 32845291 PMCID: PMC7944516 DOI: 10.1093/ecco-jcc/jjaa173] [Citation(s) in RCA: 29] [Impact Index Per Article: 5.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND AND AIMS Real-life data on long-term disease activity in Crohn's disease [CD] are scarce. Most studies describe disease course by using proxies, such as drug exposure, need for surgery or hospitalisations, and disease progression. We aimed to describe disease course by long-term disease activity and to identify distinctive disease activity patterns in the population-based IBD South Limburg cohort [IBDSL]. METHODS All CD patients in IBDSL with ≥10 years follow-up [n = 432] were included. Disease activity was defined for each yearly quarter by mucosal inflammation on endoscopy or imaging, hospitalisation, surgery, or treatment adjustment for increased symptoms. Six distinct disease activity clusters were defined. Subsequently, the associations between clinical characteristics and the patterns were assessed using multivariable logistic regression models. RESULTS On average, patients experienced 5.44 (standard deviation [SD] 3.96) quarters of disease activity during the first 10 years after diagnosis. Notably, 28.2% of the patients were classified to a quiescent pattern [≤2 active quarters in 10 years], and 89.8% of those never received immunomodulators nor biologics. Surgery at diagnosis (odds ratio [OR] 2.99; 95% confidence interval [CI] 1.07-8.34) and higher age [OR 1.03; 95% CI 1.01-1.06] were positively associated with the quiescent pattern, whereas inverse associations were observed for ileocolonic location [OR 0.44; 95% CI 0.19-1.00], smoking [OR 0.43; 95% CI 0.24-0.76] and need for steroids <6 months [OR 0.24; 95% CI 0.11-0.52]. CONCLUSIONS Considering long-term disease activity, 28.2% of CD patients were classified to a quiescent cluster. Given the complex risk-benefit balance of immunosuppressive drugs, our findings underline the importance of identifying better predictive markers to prevent both over-treatment and under-treatment.
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Affiliation(s)
- Dion Wintjens
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands,NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands,Corresponding author: Dion Wintjens, MD, Division of Gastroenterology and Hepatology, Department of Internal Medicine, NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Postbox 5800, 6202 AZ, Maastricht, The Netherlands. Tel.: 0031-43-3875021; fax: 0031-43-3875006;
| | - Francois Bergey
- Department of Research and Development, LifeGlimmer GmbH, Berlin, Germany
| | - Edoardo Saccenti
- Laboratory of Systems and Synthetic Biology, Wageningen University & Research, The Netherlands
| | - Steven Jeuring
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands,NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Tim van den Heuvel
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands,NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Mariëlle Romberg-Camps
- Department of Gastroenterology and Hepatology, Zuyderland Medical Centre, Sittard-Geleen/Heerlen, The Netherlands
| | - Liekele Oostenbrug
- Department of Gastroenterology and Hepatology, Zuyderland Medical Centre, Sittard-Geleen/Heerlen, The Netherlands
| | - Ad Masclee
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands,NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Vitor Martins dos Santos
- Department of Research and Development, LifeGlimmer GmbH, Berlin, Germany,Laboratory of Systems and Synthetic Biology, Wageningen University & Research, The Netherlands
| | - Daisy Jonkers
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands,NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
| | - Marie Pierik
- Department of Internal Medicine, Division of Gastroenterology and Hepatology, Maastricht University Medical Centre+, Maastricht, The Netherlands,NUTRIM School for Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+, Maastricht, The Netherlands
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Taborelli M, Sozzi M, Del Zotto S, Toffolutti F, Montico M, Zanier L, Serraino D. Risk of intestinal and extra-intestinal cancers in patients with inflammatory bowel diseases: A population-based cohort study in northeastern Italy. PLoS One 2020; 15:e0235142. [PMID: 32574216 PMCID: PMC7310697 DOI: 10.1371/journal.pone.0235142] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2020] [Accepted: 06/09/2020] [Indexed: 12/12/2022] Open
Abstract
The cancer risk of patients with inflammatory bowel diseases (IBD) has not been well documented in southern Europe. This study aimed to evaluate the overall pattern of cancer risk among patients with IBD in Friuli Venezia Giulia, northeastern Italy. A population-based cohort study was performed through a record linkage between local healthcare databases and the cancer registry (1995–2013). We identified 3664 IBD patients aged 18–84 years, including 2358 with ulcerative colitis (UC) and 1306 with Crohn’s disease (CD). Sex- and age-standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) were used to compare the cancer incidence of IBD patients with the general population. The cumulative cancer risk among IBD patients reached about 10% after 10 years of follow-up. A total of 246 cancers occurred among UC patients (SIR = 1.05, 95% CI: 0.92–1.19), and 141 among CD patients (SIR = 1.20, 95% CI: 1.01–1.41). As compared with the general population, no increased risk of colorectal cancers was observed for either UC or CD patients, whereas the risk of anal cancer was significantly elevated among UC patients (SIR = 6.03, 95% CI: 1.24–17.60). Increased risks were seen for specific extra-intestinal cancers, including corpus uteri (SIR = 2.67, 95% CI: 1.07–5.50) and kidney (SIR = 2.06, 95% CI: 1.03–3.69) among UC patients; thyroid (SIR = 5.58, 95% CI: 2.41–11.00) and skin non-melanoma (SIR = 1.86, 95% CI: 1.32–2.55) among CD patients. This population-based study showed that both UC and CD patients had a colorectal cancer risk similar to that of the general population. However, they were at a higher risk of developing certain extra-intestinal cancer types. Although detection biases cannot be excluded, the study findings pointed to a role of long-standing exposures to immunosuppressive therapies, underlying disease status, as well as the interactions with lifestyle factors. Our findings lent additional support to the need for monitoring the cancer burden in this at-risk population.
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Affiliation(s)
- Martina Taborelli
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
- * E-mail:
| | - Michele Sozzi
- Friuli Venezia Giulia Cancer Registry, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Stefania Del Zotto
- SC Data Warehouse, Flussi Informativi ed Epidemiologia, Agenzia Regionale di Coordinamento per la Salute, Udine, Italy
| | - Federica Toffolutti
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Marcella Montico
- Scientific Directorate, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
| | - Loris Zanier
- SC Data Warehouse, Flussi Informativi ed Epidemiologia, Agenzia Regionale di Coordinamento per la Salute, Udine, Italy
| | - Diego Serraino
- Cancer Epidemiology Unit, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
- Friuli Venezia Giulia Cancer Registry, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Aviano, Italy
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Haddad A, Al-Sabbagh MQ, Al-Ani H, Siyam AM, Aborajooh E, Iwata T, Kimura S, Shariat SF, Abufaraj M. Inflammatory bowel disease and prostate cancer risk: A systematic review. Arab J Urol 2020; 18:207-212. [PMID: 33312730 PMCID: PMC7717159 DOI: 10.1080/2090598x.2020.1761674] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/30/2022] Open
Abstract
Objective: To evaluate the risk of prostate cancer (PCa) in patients with inflammatory bowel disease (IBD), focussing on ulcerative colitis (UC) and Crohn's disease (CD) separately. Methods: A systemic search was carried out using PubMed and Web of Science databases following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We retrieved a total of 349 articles. All the articles were in the English language and investigated the incidence of PCa in patients with IBD. Results: Nine studies met our inclusion criteria, with a total of 205 037 men. Two studies reported an increase in the risk of PCa in men with IBD in general. Five other studies reported an increased risk of PCa in men with UC or with CD specifically. On the other hand, two studies reported a decreased risk of PCa in patients with UC and patients with IBD treated with aminosalicylates. Conclusions: While men with UC appear to have higher risk of developing PCa, data on patients with CD are inconclusive. Therefore, patients with UC may benefit from earlier PCa screening. Our findings confirm a complex interplay between IBD and PCa, including factors such as genetic predisposition, systemic inflammation and treatment effects. The modulatory effect of treatment strategies for IBD on the development and progression of PCa might be of clinical significance. Abbreviations: CD: Crohn's disease; CRP: C- reactive protein; FOLH1: folate hydrolase 1; GIT: gastrointestinal tract; IBD: inflammatory bowel disease; IL-6: interleukin 6; NOS: Newcastle-Ottawa Scale; PCa: prostate cancer; PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses; PSMA: prostate-specific membrane antigen; UC: ulcerative colitis.
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Affiliation(s)
- Anoud Haddad
- Division of Urology, Department of Special Surgery, Jordan University Hospital, the University of Jordan, Amman, Jordan
| | - Mohammed Qussay Al-Sabbagh
- Division of Urology, Department of Special Surgery, Jordan University Hospital, the University of Jordan, Amman, Jordan
| | - Hashim Al-Ani
- Division of Urology, Department of Special Surgery, Jordan University Hospital, the University of Jordan, Amman, Jordan
| | - Abdel Muez Siyam
- Division of Urology, Department of Special Surgery, Jordan University Hospital, the University of Jordan, Amman, Jordan
| | - Emad Aborajooh
- Department of Surgery, Faculty of Medicine, Mutah University, Kerak, Jordan
| | - Takehiro Iwata
- Department of Urology, Medical University of Vienna, Vienna, Austria.,Department of Urology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan
| | - Shoji Kimura
- Department of Urology, Medical University of Vienna, Vienna, Austria.,Department of Urology, Jikei University School of Medicine, Tokyo, Japan
| | - Shahrokh F Shariat
- Department of Urology, Medical University of Vienna, Vienna, Austria.,Department of Urology, Weill Cornell Medical College, New York, NY, USA.,Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX, USA.,Karl Landsteiner Institute of Urology and Andrology, Vienna, Austria.,Institute for Urology and Reproductive Health, Sechenov University, Moscow, Russia
| | - Mohammad Abufaraj
- Division of Urology, Department of Special Surgery, Jordan University Hospital, the University of Jordan, Amman, Jordan.,Department of Urology, Medical University of Vienna, Vienna, Austria
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Abu-Sbeih H, Wang Y. Management Considerations for Immune Checkpoint Inhibitor-Induced Enterocolitis Based on Management of Inflammatory Bowel Disease. Inflamm Bowel Dis 2020; 26:662-668. [PMID: 31560045 DOI: 10.1093/ibd/izz212] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Immune checkpoint inhibitor therapy has significantly improved the outcomes of various advanced malignancies that were deemed unruly prior to its invention. Immune-mediated diarrhea and enterocolitis are among the most frequently encountered adverse events of immune checkpoint inhibitor therapy. Given the increasing use of these therapies in the treatment of an ever-growing number of malignancies, providing appropriate treatment for such adverse effects has become crucial. METHODS In this review, we summarize the current body of evidence concerning the management of immune-mediated diarrhea and enterocolitis. Additionally, management of immune-mediated diarrhea and enterocolitis is likened to that of inflammatory bowel disease, given the resemblance between both entities in pathogenesis and clinical features. Reviewing the literature raised several points regarding this devastating toxicity that still need further investigation by future efforts. RESULTS Endoscopic and histologic evaluation is pivotal in the assessment of immune-mediated diarrhea and enterocolitis and provides vital information regarding the severity of the disease to guide treatment. Corticosteroids are the main therapy for immune-mediated diarrhea and enterocolitis, with infliximab and vedolizumab as second-line agents. Recently, fecal microbiota transplantation has emerged as a treatment option for immune-mediated diarrhea and enterocolitis that is refractory to corticosteroids. Restarting immune checkpoint inhibitor therapy after resolution of immune-mediated diarrhea and enterocolitis carries a risk of recurrence that is mostly controllable with current immune-suppressive treatment. CONCLUSIONS Lastly, we propose a management algorithm for immune-mediated diarrhea and enterocolitis. Prospective research, preferably as collaborative efforts from oncology and gastroenterology specialists, is needed to refine the management of immune-mediated diarrhea and enterocolitis.
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Affiliation(s)
- Hamzah Abu-Sbeih
- Department of Internal Medicine, The University of Missouri-Kansas City, Kansas City, Missouri, USA
| | - Yinghong Wang
- Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA
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Abstract
Evidences for the personalized use of nonsteroidal anti-inflammatory drugs (NSAIDs) in colorectal cancer (CRC) prevention and treatment that include consideration of prostaglandin E2 levels are necessary. This study was designed as a case-control study including 60 CRC patients and 120 cancer-free controls. A sensitive empirical method, precolumn derivatization HPLC, was used to determine plasma PGE2 levels. The TaqMan SNP Genotyping Assay was used for the genotyping of prostaglandin-endoperoxide synthase 2 (PTGS2) polymorphisms. Multivariate logistic regression analysis suggested that 1 log10(PGE2) increase would result in a 3.64-fold increase in the risk of CRC. Moreover, subjects with log10(PGE2) level in the 75th percentile had a significantly higher risk of CRC than those with log10(PGE2) levels in the 25th percentile [odds ratio (OR), 3.50; 95% confidence interval (CI), 1.35-9.05]. This association was more evident after adjustment for history of NSAIDs use (OR, 3.85; 95% CI, 1.46-10.16). Preliminarily, 260.02 and 414.95 pg/ml might be proposed as the preventive and warning cutoff values of plasma PGE2 for CRC. The preferred NSAIDs dose for patients with the AG+GG (rs689466) and CC+CT (rs5275) genotypes should be higher than that of patients carrying AA or TT genotypes, despite the presence of equal plasma PGE2 levels. We show for the first time that the plasma PGE2 level is associated with the risk of CRC. We provide a preliminary suggestion for NSAIDs doses adjustment according to PTGS2 genotypes after consideration of plasma PGE2 levels.
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Vulvar and vaginal neoplasia in women with inflammatory bowel disease. Dig Liver Dis 2020; 52:149-155. [PMID: 31718933 DOI: 10.1016/j.dld.2019.10.002] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/20/2019] [Revised: 09/30/2019] [Accepted: 10/02/2019] [Indexed: 02/06/2023]
Abstract
Immunosuppressive drugs are the cornerstone in the treatment of inflammatory bowel disease (IBD), however they are associated with an increased risk of extra-intestinal cancer. Whether the risk for female genital tract malignancies, including vulvar and vaginal cancer, is increased is less clear. Our aim was to investigate the risk of these malignancies in IBD-patients. Histopathological data of all IBD patients with a vulvar or vaginal (pre-)cancerous lesion were retrieved from the Dutch nationwide network and registry of histopathology and cytopathology from 1991 to 2015. Medical history was retrieved from patient records. Data from the Central Office for Statistics, the Dutch comprehensive cancer organization, and the IBDSL cohort were obtained to calculate the standardized, and age-adjusted incidence rates. Fifty-five patients met the inclusion criteria. A standardized incidence rate of 1.2(95% CI:0.8-1.7) for vulvar and vaginal carcinoma among adult female IBD was calculated, which did not significantly differ from the general population. The use of immunosuppressive therapy did not increase the occurrence of vulvovaginal malignancy, nor did it influence the recurrence rate. However, immunosuppressive drugs ever-users were on average 11 years younger at the time of their gynaecological diagnosis. Overall, our data do not support intensified screening for vulvar or vaginal malignancies in female IBD patients.
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Card T, Ungaro R, Bhayat F, Blake A, Hantsbarger G, Travis S. Vedolizumab use is not associated with increased malignancy incidence: GEMINI LTS study results and post-marketing data. Aliment Pharmacol Ther 2020; 51:149-157. [PMID: 31747086 PMCID: PMC7050439 DOI: 10.1111/apt.15538] [Citation(s) in RCA: 25] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2019] [Revised: 09/01/2019] [Accepted: 09/23/2019] [Indexed: 12/13/2022]
Abstract
BACKGROUND Vedolizumab is a gut-selective antibody to α4 β7 integrin approved to treat moderate-to-severe Crohn's disease and ulcerative colitis in adults. Inflammatory bowel disease (IBD) and immunosuppressant use are associated with increased risk of malignancy. AIM To analyse the incidence of malignancy with vedolizumab treatment in the GEMINI long-term safety (LTS) study and post-marketing (PM) setting. METHODS Malignancy data from the LTS study (May 2009 to May 2018), and data from the vedolizumab Global Safety Database (20 May 2014 to 19 May 2018), were identified using Medical Dictionary for Regulatory Activities coding. The number of patients experiencing malignancies in the LTS study (excluding malignancies within 1 year following vedolizumab initiation) was indirectly standardised against the number expected, using age- and sex-specific rates in patients with IBD from Optum's Clinformatics™ Data Mart (CDM) database. RESULTS Among 1785 patients with ≥1 year of follow-up post-vedolizumab initiation in the LTS study (total 5670 patient-years), observed numbers of malignancies were similar to those expected compared with CDM data (31 vs 29; ratio of observed to expected events = 1.08; P = 0.71; 95% confidence intervals [CI] 0.73, 1.53). The most common malignancies were renal and bladder (6). PM, 293 patients reported 299 malignancies (including malignancies within 1 year following vedolizumab initiation), in approximately 208 050 patient-years of vedolizumab exposure. Lower gastrointestinal malignancies were most common (59). CONCLUSIONS The number of malignancies in the LTS study was similar to that expected from an IBD population with no statistically significant differences, although few confounders could be corrected for. Limitations of PM safety reporting require consideration; however, the number of malignancies with vedolizumab appeared low.
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Affiliation(s)
- Timothy Card
- Faculty of Medicine and Health Sciences, University of Nottingham, Nottingham, UK
| | - Ryan Ungaro
- The Henry D. Janowitz Division of Gastroenterology, Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | - Fatima Bhayat
- Takeda Pharmaceuticals International Co., Cambridge, MA, USA
| | - Aimee Blake
- Takeda Pharmaceuticals International Co., Cambridge, MA, USA
| | | | - Simon Travis
- Translational Gastroenterology Unit, NIHR Oxford Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, 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: 56] [Impact Index Per Article: 9.3] [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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44
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Ge Y, Shi Q, Yao W, Cheng Y, Ma G. The association between inflammatory bowel disease and prostate cancer risk: a meta-analysis. Prostate Cancer Prostatic Dis 2019; 23:53-58. [PMID: 31591455 DOI: 10.1038/s41391-019-0177-7] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/13/2019] [Revised: 08/07/2019] [Accepted: 08/26/2019] [Indexed: 12/17/2022]
Abstract
BACKGROUND Patients with inflammatory bowel disease (IBD) are at increased risk of gastrointestinal and extraintestinal malignancies. However, the associations between IBD and prostate cancer (PCa) risk remain conflicting. METHODS We conducted a systematic literature search in PubMed, EMBASE, and Web of Science databases. According to the inclusion and exclusion criteria, a total of nine studies were included in the meta-analysis. The pooled standardized incidence ratios (SIRs) or relative risks (RRs) and corresponding 95% confidence intervals (CIs) were calculated to determine the relationship of IBD and PCa risk. RESULTS For cohort studies, the pooled SIR was 1.33 (95% CI = 1.03-1.71). The further subgroup analysis showed that the PCa risk was higher in patients with ulcerative colitis (UC) (pooled SIR = 1.58, 95% CI = 1.08-2.30), but not in patients with Crohn's disease (CD) (pooled SIR = 1.12, 95% CI = 0.97-1.31). Besides, for the three case-control studies, the results indicated that compared with normal group, the pooled RR of PCa was 1.81 for the patients with IBD (95% CI = 1.43-2.29). In addition, sensitivity analysis indicated that the results were robust and no significant publication bias were observed. CONCLUSIONS Our findings based on the large and multicenter samples strongly indicated that men with IBD especial UC have significantly elevated PCa risk. Future efforts are needed to define the mechanism underlying the link between IBD and PCa or clinically significant PCa risk.
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Affiliation(s)
- Yuqiu Ge
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, China
| | - Qianqian Shi
- Department of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, China
| | - Wenxi Yao
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, China
| | - Yang Cheng
- Department of Public Health and Preventive Medicine, Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, Jiangsu, China.
| | - Gaoxiang Ma
- Clinical Metabolomics Center, China Pharmaceutical University, Nanjing, 211198, China. .,State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing, China.
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45
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Smeets FGM, Liedorp PR, van der Poel M, Miclea RL, Masclee AAM, Pierik M. Anaplastic Large Cell T Cell Lymphoma in a Patient With Severe Therapy-refractory Crohn's Disease on Long-standing Immunosuppressive Medication During Ustekinumab Treatment: A Case Report and Review of the Literature. J Crohns Colitis 2019; 13:1470-1473. [PMID: 31116402 PMCID: PMC7142401 DOI: 10.1093/ecco-jcc/jjz084] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
Use of ustekinumab in Crohn's disease was approved in 2016, and consequently data regarding its real-world safety are still limited. We here present a 29-year-old woman with severe therapy-refractory Crohn's disease, who developed an anaplastic large cell T cell lymphoma during treatment with ustekinumab.
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Affiliation(s)
- Fabiënne G M Smeets
- Division of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands,Corresponding author: F. G. M. Smeets, Msc, Division of Gastroenterology and Hepatology, Department of Internal Medicine, P. Debyelaan 25, 6229 HX Maastricht, The Netherlands. Tel.: +31433875021; Fax: +31433875006;
| | - Paulien R Liedorp
- Division of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands,Division of Gastroenterology and Hepatology, VieCuri Medical Center, Venlo, The Netherlands
| | - Marjolein van der Poel
- Division of Hematology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Razvan L Miclea
- Department of Radiology and Nuclear Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Ad A M Masclee
- Division of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
| | - Marieke Pierik
- Division of Gastroenterology and Hepatology, Maastricht University Medical Center, Maastricht, The Netherlands
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Burns JA, Weiner AB, Kundu S. Reply to Zeynep G. Gul, Alberto Martini, and Carl A. Olsson's Letter to the Editor re: Jacob A. Burns, Adam B. Weiner, William J. Catalona, et al. Inflammatory Bowel Disease and the Risk of Prostate Cancer. Eur Urol 2019;75:846-52. Eur Urol 2019; 76:e99-e100. [PMID: 31151679 DOI: 10.1016/j.eururo.2019.05.027] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2019] [Accepted: 05/17/2019] [Indexed: 11/27/2022]
Affiliation(s)
- Jacob A Burns
- Department of Urology, Northwestern Medicine, Chicago, IL, USA
| | - Adam B Weiner
- Department of Urology, Northwestern Medicine, Chicago, IL, USA
| | - Shilajit Kundu
- Department of Urology, Northwestern Medicine, Chicago, IL, USA.
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47
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Abstract
Crohn's disease is associated with various intestinal and extraintestinal malignancies. This article reviews the current literature regarding Crohn's disease and subsequent risk of cancer formation. Recognition of risk factors (both modifiable and unmodifiable) is essential for prevention and appropriate screening. Future investigations into the molecular mechanisms associated with Crohn-related malignancy will provide additional insight into carcinogenesis, potential for early intervention, and identification of at-risk patients.
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Affiliation(s)
- Evie Carchman
- Department of Surgery, University of Wisconsin, Madison, Wisconsin
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48
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Gul ZG, Martini A, Olsson CA. Re: Jacob A. Burns, Adam B. Weiner, William J. Catalone, et al. Inflammatory Bowel Disease and the Risk of Prostate Cancer. Eur Urol 2019;75:846-52. Eur Urol 2019; 76:e98. [PMID: 31160097 DOI: 10.1016/j.eururo.2019.05.026] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/13/2019] [Accepted: 05/17/2019] [Indexed: 11/18/2022]
Affiliation(s)
- Zeynep G Gul
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
| | | | - Carl A Olsson
- Icahn School of Medicine at Mount Sinai, New York, NY, USA
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49
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Huang SZ, Liu ZC, Liao WX, Wei JX, Huang XW, Yang C, Xia YH, Li L, Ye C, Dai SX. Risk of skin cancers in thiopurines-treated and thiopurines-untreated patients with inflammatory bowel disease: A systematic review and meta-analysis. J Gastroenterol Hepatol 2019; 34:507-516. [PMID: 30393891 DOI: 10.1111/jgh.14533] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/13/2018] [Revised: 10/23/2018] [Accepted: 10/26/2018] [Indexed: 12/27/2022]
Abstract
BACKGROUND AND AIM The thiopurines are effective in the management of patients with inflammatory bowel disease (IBD), but the association between thiopurines use and the risk of skin cancer (including nonmelanoma skin cancer [NMSC] and melanoma skin cancer) has already been sufficiently reported. However, the results of these studies are inconsistent, and thus, the objective of our analysis was to explore whether thiopurines can lead to an excess risk of skin cancer in IBD patients. METHODS MEDLINE, EMBASE, and the Cochrane Library were searched to identify relevant studies that evaluated the risk of skin cancer in IBD patients treated with thiopurines. A random effects meta-analysis was conducted to calculate the pooled incidence rate ratios as well as risk ratios (RRs). Subgroup analysis was performed to explore the potential source of heterogeneity. RESULTS Thirteen studies comprising 149 198 participants were included. The result suggested that thiopurines significantly increased the risk of overall skin cancer in IBD patients (random effects: RR = 1.80, 95% confidence interval [CI] 1.14-2.87, P = 0.013), among which NMSC showed an excess risk associated with thiopurines use (random effects: RR = 1.88, 95% CI 1.48-2.38, P < 0.001) while no increased risk was observed with respect to melanoma skin cancer (random effects: RR = 1.22, 95% CI 0.90-1.65, P = 0.206). Subgroup analysis regarding sample size and geographic distribution in skin cancer and follow-up duration in NMSC reached statistical significance, while other subgroups showed no significance. CONCLUSION Exposition of thiopurines in patients with IBD is associated with a higher risk of skin cancer. Routine skin screening and daily skin protective practice are recommended for these patients.
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Affiliation(s)
- Shao-Zhuo Huang
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Zhi-Cheng Liu
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Wei-Xin Liao
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Jun-Xiao Wei
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Xiao-Wen Huang
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Chen Yang
- The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, China
| | - Yu-Han Xia
- Basic Medical College, Southern Medical University, Guangzhou, Guangdong, China
| | - Lu Li
- Department of Plastic Surgery, Changhai Hospital, Second Military Medical University, Shanghai, China
| | - Chao Ye
- Basic Medical College, Navy Medical University, Shanghai, China
| | - Shi-Xue Dai
- Department of Gastroenterology, Guangdong General Hospital and Guangdong Academy of Medical Sciences, South China University of Technology, Guangzhou, Guangdong, China.,Guangdong Geriatrics Institute, Guangdong General Hospital and Guangdong Academy of Medical Sciences, South China University of Technology, Guangzhou, Guangdong, China
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50
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Keller DS, Windsor A, Cohen R, Chand M. Colorectal cancer in inflammatory bowel disease: review of the evidence. Tech Coloproctol 2019; 23:3-13. [PMID: 30701345 DOI: 10.1007/s10151-019-1926-2] [Citation(s) in RCA: 173] [Impact Index Per Article: 28.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Accepted: 01/13/2019] [Indexed: 02/06/2023]
Abstract
Inflammatory bowel disease (IBD)-related colorectal cancer (CRC) is responsible for approximately 2% of the annual mortality from CRC overall, but 10-15% of the annual deaths in IBD patients. IBD-related CRC patients are also affected at a younger age than sporadic CRC patients, and have a 5-year survival rate of 50%. Despite optimal medical treatment, the chronic inflammatory state inherent in IBD increases the risk for high-grade dysplasia and CRC, with additional input from genetic and environmental risk factors and the microbiome. Recognizing risk factors, implementing appropriate surveillance, and identifying high-risk patients are key to managing the CRC risk in IBD patients. Chemoprevention strategies exist, and studies evaluating their efficacy are underway. Once dysplasia or invasive cancer is diagnosed, appropriate surgical resection and postoperative treatment and surveillance are necessary. Here, we discuss the current state of IBD-related CRC, prevalence, risk factors, and evidence for surveillance, prophylaxis, and treatment recommendations.
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Affiliation(s)
- D S Keller
- Division of Colon and Rectal Surgery, Department of Surgery, NewYork-Presbyterian, Columbia University Medical Center, Herbert Irving Pavilion, 161 Fort Washington Avenue, 8th Floor, New York, NY, 10032, USA.
| | - A Windsor
- Department of Surgery and Interventional Sciences, University College London Hospitals, NHS Foundation Trust, London, UK
| | - R Cohen
- Department of Surgery and Interventional Sciences, University College London Hospitals, NHS Foundation Trust, London, UK
| | - M Chand
- GENIE Centre, University College London, London, UK
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