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Singh A, Khanna T, Mahendru D, Kahlon J, Kumar V, Sohal A, Yang J. Insights into renal and urological complications of inflammatory bowel disease. World J Nephrol 2024; 13:96574. [PMID: 39351187 PMCID: PMC11439091 DOI: 10.5527/wjn.v13.i3.96574] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/13/2024] [Revised: 07/01/2024] [Accepted: 07/15/2024] [Indexed: 09/19/2024] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic condition characterized by immune-mediated inflammation in the gastrointestinal tract, which follows a relapsing and remitting course. Apart from affecting the gastrointestinal tract, IBD also has extra-intestinal manifestations (EIMs). While the etiology of extraintestinal manifestation remains unclear, it is theorized to be based on immunological responses influenced by genetic factors. Renal involvement is one of the EIMs observed in ulcerative colitis and Crohn's disease. The renal manifestations in IBD patients encompass a range of conditions including nephrolithiasis, amyloidosis, tubulointerstitial nephritis, glomerulonephritis (GN), obstructive pathologies, and chronic kidney disease (CKD). The incidence of CKD in IBD patients varies from 5%-15%. The decline in renal function can stem from various factors such as direct inflammatory damage to the kidneys leading to glomerular or tubular injury, or from complications like recurrent stones, amyloidosis, or GN. Additionally, nephrotoxic medications used in treating IBD, such as TNF-α inhibitors, calcineurin inhibitors, and aminosalicylates, can exacerbate the decline in renal function. Currently, there is a lack of consensus regarding these patients' screening and renal function monitoring. This review aims to assess the existing literature on the different renal complications among individuals with IBD, shedding light on their pathophysiology and management.
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Affiliation(s)
- Anmol Singh
- Department of Medicine, Tristar Centennial Medical Center, Nashville, TN 37203, United States
| | - Tejasvini Khanna
- Department of Medicine, Maulana Azad Medical College, New Delhi 110002, India
| | - Diksha Mahendru
- Department of Medicine, Dayanand Medical College and Hospital, Ludhiana 141001, Punjab, India
| | - Jasraj Kahlon
- Department of Internal Medicine, Abrazo Medical Center, Phoenix, AZ 85015, United States
| | - Vikash Kumar
- Department of Medicine, The Brooklyn Hospital Center, Brooklyn, NY 11201, United States
| | - Aalam Sohal
- Department of Hepatology, Liver Institute Northwest, Seattle, WA 98105, United States
| | - Juliana Yang
- Division of Gastroenterology and Hepatology, University of Texas Medical Branch, Galveston, TX 77555, United States
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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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Liu J, Wu P, Lai S, Wang J, Wang J, Zhang Y. Identifying possible hub genes and biological mechanisms shared between bladder cancer and inflammatory bowel disease using machine learning and integrated bioinformatics. J Cancer Res Clin Oncol 2023; 149:16885-16904. [PMID: 37740761 DOI: 10.1007/s00432-023-05266-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/16/2023] [Accepted: 08/08/2023] [Indexed: 09/25/2023]
Abstract
BACKGROUND Recent studies have shown that inflammatory bowel disease (IBD) is associated with bladder cancer (BC) incidence. But there is still a lack of understanding regarding its pathogenesis. Thus, this study aimed to identify potential hub genes and their important pathways and pathological mechanisms of interactions between IBD and BC using bioinformatics methods. METHODS The data from Gene Expression Omnibus (GEO) and the cancer genome atlas (TCGA) were analyzed to screen common differentially expressed genes (DEGs) between IBD and BC. The "clusterProfiler" package was used to analyze GO term and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment in DEGs. After that, we conducted a weighted gene co-expression network analysis (WGCNA) on these DEGs to determine the vital modules and genes significantly related to BC. Protein-protein interaction (PPI) networks was used to identify hub genes. Further, the hub genes were used to develop a prognostic signature by Cox analysis. The validity of the ten hub DEGs was tested using three classification algorithms. Finally, we analyzed the microRNAs (miRNA)-mRNA, transcription factors (TFs)-mRNA regulatory network. RESULTS Positive regulation of organelle fission, chromosomal region, tubulin binding, and cell cycle signaling pathway were the major enriched pathways for the common DEGs. PPI networks identified three hub proteins (AURKB, CDK1, and CCNA2) with high connectivity. Three machine-learning classification algorithms based on ten hub genes performed well for IBD and BC (accuracy > 0.80). The robust predictive model based on the ten hub genes could accurately classify BC cases with various clinical outcomes. Based on the gene-TFs and gene-miRNAs network construction, 9 TFs and 6 miRNAs were identified as potential critical TFs and miRNAs. There are 13 drugs that interact with the hub gene based on gene-drug interaction analysis. CONCLUSIONS This study explored common gene signatures and the potential pathogenesis of IBD and BC. We revealed that an unbalanced immune response, cell cycle pathway, and neutrophil infiltration might be the common pathogenesis of IBD and BC. Molecular mechanisms for the treatment of IBD and CC still require further investigation.
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Affiliation(s)
- Jianyong Liu
- Department of Urology, Institute of the Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China
- Beijing Hospital Continence Center, Beijing, People's Republic of China
| | - Pengjie Wu
- Department of Urology, Institute of the Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China
- Beijing Hospital Continence Center, Beijing, People's Republic of China
| | - Shicong Lai
- Department of Urology, Peking University People's Hospital, Beijing, 100044, People's Republic of China
| | - Jianye Wang
- Department of Urology, Institute of the Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Beijing Hospital Continence Center, Beijing, People's Republic of China.
- , No. 1 DaHua Road, Dong Dan, Beijing, 100730, China.
| | - Jianlong Wang
- Department of Urology, Institute of the Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Beijing Hospital Continence Center, Beijing, People's Republic of China.
- , No. 1 DaHua Road, Dong Dan, Beijing, 100730, China.
| | - Yaoguang Zhang
- Department of Urology, Institute of the Geriatric Medicine, Beijing Hospital, National Center of Gerontology, Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Graduate School of Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People's Republic of China.
- Beijing Hospital Continence Center, Beijing, People's Republic of China.
- , No. 1 DaHua Road, Dong Dan, Beijing, 100730, China.
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Wang L, Deng JY, Li KP, Shan-Yin, Zhu PY. Inflammatory bowel disease and bladder cancer risk: based on a Mendelian randomization study. BMC Urol 2023; 23:195. [PMID: 38012665 PMCID: PMC10683281 DOI: 10.1186/s12894-023-01346-y] [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: 06/28/2023] [Accepted: 10/20/2023] [Indexed: 11/29/2023] Open
Abstract
BACKGROUND Prior epidemiological observational studies have duly documented a correlative link between inflammatory bowel disease (IBD) and bladder cancer (BC); however, the establishment of a definitive causal relationship has remained elusive. The principal objective of this meticulous investigation was to rigorously evaluate the causal nexus between IBD and BC, employing the robust methodology of Mendelian randomization (MR) analysis. METHODS We meticulously performed both univariate and multivariate Mendelian randomization (MVMR) analyses employing publicly accessible genome-wide association study (GWAS) data. The central approach employed for our investigations was inverse variance weighting (IVW) method, while diligently scrutinizing potential sources of heterogeneity and horizontal pleiotropy via the rigorous utilization of Cochran's Q test, the MR-PRESSO method, and MR-Egger. RESULTS In the univariate MR analysis, no causal link was observed between genetic prediction of IBD and BC. Furthermore, both Crohn's disease (CD) and ulcerative colitis (UC) showed no causal association with BC. The consistent association between CD and UC in the MVMR analysis supports this finding. CONCLUSION This study found no genetic basis for the causative association of IBD and BC. It is crucial to emphasize that further comprehensive investigations are warranted to delve into the intricate underlying mechanisms that may contribute to these associations.
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Affiliation(s)
- Li Wang
- Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Jing-Ya Deng
- Department of Neurology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Kun-Peng Li
- Department of Urology, The Second Hospital of Lanzhou University, Lanzhou, China
| | - Shan-Yin
- Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China
| | - Ping-Yu Zhu
- Department of Urology, Affiliated Hospital of North Sichuan Medical College, Nanchong, China.
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Massano A, Bertin L, Zingone F, Buda A, Visaggi P, Bertani L, de Bortoli N, Fassan M, Scarpa M, Ruffolo C, Angriman I, Bezzio C, Casini V, Ribaldone DG, Savarino EV, Barberio B. Extraintestinal Cancers in Inflammatory Bowel Disease: A Literature Review. Cancers (Basel) 2023; 15:3824. [PMID: 37568640 PMCID: PMC10417189 DOI: 10.3390/cancers15153824] [Citation(s) in RCA: 6] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/25/2023] [Revised: 07/24/2023] [Accepted: 07/25/2023] [Indexed: 08/13/2023] Open
Abstract
BACKGROUND Inflammatory bowel disease (IBD) is a group of chronic multifactorial inflammatory disorders including two major entities: Crohn's disease (CD) and ulcerative colitis (UC). Preliminary evidence suggests that patients with IBD may be at increased risk of developing intestinal and extraintestinal cancers (EICs). Actually, little is known about the association between IBD and EICs, and there is ever-growing concern regarding the safety of immunomodulators and biological therapy, which may represent a risk factor for carcinogenesis. AIMS The aim of this review is to summarize the evidence regarding the association between IBD and EICs, the safety of immunomodulators and biological therapy and the management of immunomodulators and biologic agents in IBD patients with prior or current EICs. RESULTS IBD patients have a higher risk of developing different forms of extraintestinal solid organ tumors and hematological malignancies. Immunomodulators and biological therapy may increase the risk of developing some types of EICs and may be consciously used in patients with IBD and current or prior history of malignancy. CONCLUSIONS Decisions regarding the use of immunomodulators or biological therapies should be made on an individual basis, considering a multidisciplinary approach involving oncologists.
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Affiliation(s)
- Alessandro Massano
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Luisa Bertin
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Fabiana Zingone
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Andrea Buda
- Gastroenterology Unit, Department of Gastrointestinal Oncological Surgery, S. Maria del Prato Hospital, 32032 Feltre, Italy;
| | - Pierfrancesco Visaggi
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (P.V.); (L.B.); (N.d.B.)
| | - Lorenzo Bertani
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (P.V.); (L.B.); (N.d.B.)
| | - Nicola de Bortoli
- Gastroenterology Unit, Department of Translational Research and New Technologies in Medicine and Surgery, University of Pisa, 56126 Pisa, Italy; (P.V.); (L.B.); (N.d.B.)
| | - Matteo Fassan
- Surgical Pathology Unit, Department of Medicine, University of Padova, 35138 Padova, Italy;
| | - Marco Scarpa
- General Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padova, Italy; (M.S.); (C.R.); (I.A.)
| | - Cesare Ruffolo
- General Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padova, Italy; (M.S.); (C.R.); (I.A.)
| | - Imerio Angriman
- General Surgery Unit, Department of Surgery, Oncology and Gastroenterology, University of Padova, 35138 Padova, Italy; (M.S.); (C.R.); (I.A.)
| | - Cristina Bezzio
- IBD Center, Gastroenterology Unit, Rho Hospital, ASST Rhodense, 20017 Rho, Italy;
| | | | - Davide Giuseppe Ribaldone
- Department of Medical Sciences, Division of Gastroenterology, University of Turin, 10126 Turin, Italy;
| | - Edoardo Vincenzo Savarino
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
| | - Brigida Barberio
- Gastroenterology Unit, Department of Surgery, Oncology and Gastroenterology, University Hospital of Padova, 35128 Padova, Italy; (A.M.); (L.B.); (F.Z.); (B.B.)
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Tulewicz-Marti E, Stępień-Wrochna B, Maciejewska K, Łodyga M, Karłowicz K, Lewandowski K, Rydzewska G. Awareness and Compliance with the Recommendations of Primary and Secondary Prevention of Cancer in Patients with Inflammatory Bowel Disease. J Pers Med 2023; 13:913. [PMID: 37373902 DOI: 10.3390/jpm13060913] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Revised: 05/23/2023] [Accepted: 05/27/2023] [Indexed: 06/29/2023] Open
Abstract
INTRODUCTION Patients with Inflammatory Bowel Disease (IBD), including Crohn's disease (CD) and ulcerative colitis (UC), are at high risk of developing malignancies, so prevention and adherence to cancer screening may improve detection. The aim of this study was to assess compliance with medical recommendations, especially primary and secondary prevention of cancer. METHODS This one-center cross-sectional study was carried out between June and December 2021 amongst patients at the Department of Internal Medicine and Gastroenterology, IBD Division, National Medical Institute of Ministry of Interior Affairs and Administrations, or the outpatient clinic. Patients with IBD were asked to complete an anonymous questionnaire, which included 42 questions concerning lifestyle, cancer risk factors, cancer history, and checkups. STATISTICAL METHODS The results of the qualitative variables were expressed as frequencies and percentages. We used Fisher's exact test and the Chi-squared test. A value of p < 0.05 was considered significant. Statistical analyses were performed with the SPSS statistical package. RESULTS A total of 313 patients were enrolled in the study: 145 women and 168 men. In the group, 182 had Crohn's disease (CD), 120 had ulcerative colitis (UC), and 11 with IBDU (unclassified IBD). Most participants had a disease duration of over 8 years and received biological treatment, corticoids, and/or immunosuppressive therapy. Amongst respondents, 17% (31) of patients with CD and 25.8% (31) with UC were overweight, and 10.5% (19) with CD and 15.8% (19) with UC were obese (p = 0.017). We found that 16.3% of all respondents were smokers (79.6% (144) with CD, 90.8% (109) with UC, and 72.7% (8) with IBDU; p = 0.053), and 33.9% declared that they consumed alcohol (39.4% (71) with CD, 26.9% (32) with UC, and 18.2% (2) with IBDU; p = 0.045). A total of 25.4% of patients were exposed to UV radiation, but only 18.8% used sunblock. In addition, 58.8% (67) of patients with CD and 35.8% (19) with UC receiving immunosuppressants had regular laboratory tests (p = 0.02). Furthermore, 41.4% (46) of patients with UC, 27.1% (49) of patients with CD, and 70.0% (7) of patients with IBDU declared not to perform any dermatological control (p = 0.013). A total of 77% of patients had abdominal ultrasound. Out of 52.9% of patients for whom colonoscopy was recommended, only 27.3% had it performed (16.9% (30) with CD vs. 43.1% (50) with UC p < 0.001). Most examinations were ordered by gastroenterologists. Female patients had regular breast control (CD, 78.6% (66); UC, 91.2% (52); IBDU, 50% (2); p = 0.034), and 93.8% (76) had gynecological examinations. Additionally, 80.2% of patients knew about HPV, but most declared not to be vaccinated. A total of 17.9% of patients had urological control, but most had no important pathology detected. CONCLUSIONS According to our study, many patients are still exposed to risk factors, such as obesity, smoking, and low physical activity, that are modifiable. Laboratory tests in patients with immunosuppressive treatment should be performed regularly. Systematic control, especially dermatological checkups, should be recommended. Additionally, not only gastrologists but also other specialists and GPs should remind patients about regular checkups. Primary prevention, such as HPV vaccinations, should be recommended to all patients.
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Affiliation(s)
- Edyta Tulewicz-Marti
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Unit, National Medical Institute of the Ministry of Interior Affairs and Administration-Warsaw, 02-507 Warsaw, Poland
| | - Beata Stępień-Wrochna
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Unit, National Medical Institute of the Ministry of Interior Affairs and Administration-Warsaw, 02-507 Warsaw, Poland
| | - Katarzyna Maciejewska
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Unit, National Medical Institute of the Ministry of Interior Affairs and Administration-Warsaw, 02-507 Warsaw, Poland
| | - Michał Łodyga
- Internal Medicine Department, Grochowski Hospital, 04-073 Warsaw, Poland
- Department of Internal Medicine, Faculty of Health Science, Medical University of Warsaw, 02-091 Warszawa, Poland
| | - Katarzyna Karłowicz
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Unit, National Medical Institute of the Ministry of Interior Affairs and Administration-Warsaw, 02-507 Warsaw, Poland
| | - Konrad Lewandowski
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Unit, National Medical Institute of the Ministry of Interior Affairs and Administration-Warsaw, 02-507 Warsaw, Poland
| | - Grazyna Rydzewska
- Department of Internal Medicine and Gastroenterology with Inflammatory Bowel Disease Unit, National Medical Institute of the Ministry of Interior Affairs and Administration-Warsaw, 02-507 Warsaw, Poland
- Collegium Medicum, Jana Kochanowski University, 25-317 Kielce, Poland
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Nakada T, Arihiro S, Gunji T, Ogasawara Y, Kato M, Kato T, Ikegami M, Yano S, Hokari A, Saruta M. A rare case of Epstein-Barr virus-positive diffuse large B-cell lymphoma, not otherwise specified, in a patient with ulcerative colitis. Clin J Gastroenterol 2023:10.1007/s12328-023-01811-z. [PMID: 37204601 DOI: 10.1007/s12328-023-01811-z] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/23/2022] [Accepted: 04/29/2023] [Indexed: 05/20/2023]
Abstract
While colorectal cancer is a likely complication associated with inflammatory bowel diseases such as ulcerative colitis, malignant lymphoma occurs less frequently. We report the case of a patient with ulcerative colitis having Epstein-Barr virus-positive diffuse large B-cell lymphoma, not otherwise specified (EBV + DLBCL, NOS), which was maintained in clinical remission with 5-aminosalicylic acid. The patient had received a diagnosis of total ulcerative colitis 5 years ago. A recent colonoscopy revealed a 35 mm protruding lesion with depression in the sigmoid colon, and histopathological examination confirmed the presence of EBV + DLBCL, NOS. The patient has undergone six courses of chemotherapy without recurrence of lymphoma and will continue to be monitored periodically. Patients with ulcerative colitis must be followed up with periodic colonoscopies and imaging studies regardless of their background, treatment, and symptoms to ensure the prevention of complications. Furthermore, while special attention must be paid to the commonly occurring colorectal cancer on account of its association with the patient's prognosis, the possibility of the incidence of malignant lymphoma must not be ignored.
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Affiliation(s)
- Tatsuya Nakada
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University, Katsushika Medical Center, 6-41-2 Aoto, Katsushika-Ku, Tokyo, 105-8461, Japan
| | - Seiji Arihiro
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University, Katsushika Medical Center, 6-41-2 Aoto, Katsushika-Ku, Tokyo, 105-8461, Japan.
| | - Tadahiro Gunji
- Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Yoji Ogasawara
- Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Masayuki Kato
- Department of Endoscopy, The Jikei University School of Medicine, Tokyo, Japan
| | - Tomohiro Kato
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
- Center for Preventive Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Masahiro Ikegami
- Department of Pathology, Katsushika Medical Center, The Jikei University, Tokyo, Japan
| | - Shingo Yano
- Division of Clinical Oncology and Hematology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
| | - Atsushi Hokari
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University, Katsushika Medical Center, 6-41-2 Aoto, Katsushika-Ku, Tokyo, 105-8461, Japan
| | - Masayuki Saruta
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, The Jikei University School of Medicine, Tokyo, Japan
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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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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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10
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Adamek HE, Hommelsheim A. [Intestinal and extraintestinal malignancies in inflammatory bowel disease: case series from a tertiary center]. ZEITSCHRIFT FUR GASTROENTEROLOGIE 2021; 60:320-325. [PMID: 34820805 DOI: 10.1055/a-1672-4861] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 10/19/2022]
Abstract
Inflammatory bowel diseases have recorded increasing incidence. A long period of illness and immunsuppressive drugs run a high risk of complications, this is particularly true for neoplasias.Medical records of patients with inflammatory bowel diseases who developed a malignant disease during 2000 and 2020 were used for analysis.51 patients could be included. 56% of tumors were located extraintestinal and occurred more often in patient with Crohn's disease. Neoplasias were more frequent in men (61 %).Individual prevention recommendations are urgently needed. Our focus should be extended to extraintestinal neoplasias. Initial diagnosis is often made in the 50+ age group. Thus, standardizised prevention programs including life-style factors should be started at the time of IBD diagnosis.
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11
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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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12
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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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13
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Kuriakose Kuzhiyanjal AJ, Nigam GB, Afzal M. Amelanotic anorectal malignant melanoma in an ulcerative colitis patient: a rare coincidence or a rare association. BMJ Case Rep 2021; 14:14/3/e240398. [PMID: 33727297 PMCID: PMC7970289 DOI: 10.1136/bcr-2020-240398] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/03/2022] Open
Abstract
Inflammatory bowel disease (IBD) is a chronic inflammatory disorder of the gastrointestinal system, known to be associated with increased risk of carcinogenesis. We report the case of a 55-year-old woman, presenting with symptoms of increased bowel frequency, per rectal bleeding and rectal pain with a background of ulcerative colitis (UC). This was presumptively managed as UC flare, with titration of her medications to control the symptoms. However, a flexible sigmoidoscopy revealed an ulceroproliferative lesion in the rectum, which was identified as an amelanotic anorectal malignant melanoma on immunohistochemistry. No local or distant metastases were noted on radiological imaging. The tumour enlarged progressively and was managed with laparotomy and defunctioning stoma followed by palliative chemotherapy and immunotherapy. This is the first such case reported in literature, highlighting the importance of endoscopic assessment and the need to consider other differential diagnosis in patients with symptoms of IBD flare.
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Affiliation(s)
| | - Gaurav Bhaskar Nigam
- Gastroenterology, The Royal Oldham Hospital, The Pennine Acute Hospitals NHS Trust, Manchester, UK
| | - Muhammad Afzal
- Gastroenterology, The Royal Oldham Hospital, The Pennine Acute Hospitals NHS Trust, Manchester, UK
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14
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Rao RR, Majlessipour F, Ziring DA, Baca NM. Ewing's Sarcoma in a Patient with Crohn's Disease Treated with Ustekinumab: A Case Report. J Adolesc Young Adult Oncol 2020; 10:614-617. [PMID: 32960134 DOI: 10.1089/jayao.2020.0077] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022] Open
Abstract
Biologic therapies have revolutionized the treatment of immune-mediated diseases. They are generally well tolerated; however, there are reports of malignancies associated with the use of these drugs. This case is of an adolescent with refractory Crohn's disease treated with ustekinumab, who subsequently developed Ewing's sarcoma. Patients treated with ustekinumab have reportedly developed B cell lymphoma, epithelioid sarcoma, as well as cancer of the lung, esophagus, ovary, testis, kidney, and thyroid. However, this is the first documented case of a patient treated with ustekinumab to develop Ewing sarcoma.
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Affiliation(s)
- Rameshwar R Rao
- Department of Pediatrics, David Geffen School of Medicine, University of California, Los Angeles, California, USA
| | - Fataneh Majlessipour
- Department of Pediatric Hematology-Oncology and Cedars Sinai Medical Center, Los Angeles, California, USA
| | - David A Ziring
- Department of Pediatric Gastroenterology, Cedars Sinai Medical Center, Los Angeles, California, USA
| | - Nicole M Baca
- Department of Pediatric Hematology-Oncology and Cedars Sinai Medical Center, Los Angeles, California, USA
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15
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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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16
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Mine S, Takeshima F, Akazawa Y, Matsushima K, Minami H, Yamaguchi N, Ohnita K, Isomoto H, Nakao K. Correlation of Fecal Markers with Magnifying Endoscopic Stratification in Patients with Ulcerative Colitis Who Are in Clinical Remission. Digestion 2018; 97:82-89. [PMID: 29393146 DOI: 10.1159/000484223] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Maintenance of mucosal healing is recommended during the treatment of ulcerative colitis (UC). However, symptoms of UC often do not reflect mucosal disease activity. Fecal markers such as calprotectin, lactoferrin, and hemoglobin have been reported to correlate well with the Mayo endoscopic subscore (MES) and are being considered alternative monitoring tools in endoscopy. Ulcerative Colitis Endoscopic Index of Severity (UCEIS) is a new and more detailed endoscopic scoring system compared to MES. Furthermore, magnifying endoscopic stratification (ME) based on alterations in the mucosal surface pit patterns is noted in UC. However, the association between fecal markers and UCIES and magnifying endoscopy is relatively unexplored. SUMMARY This study investigated the association between the aforementioned fecal markers and MES, UCEIS, and ME in patients with UC in clinical remission. This prospective study included 60 patients with UC in clinical remission who underwent colonoscopy at the Nagasaki University Hospital between June 2015 and November 2016. A significant correlation was observed between MES and all fecal markers. Notably, the fecal markers correlated well with UCEIS (calprotectin Spearman's correlation coefficient [r] = 0.54, p < 0.0001; lactoferrin r = 0.56, p < 0.0001; and hemoglobin r = 0.43, p < 0.001). Furthermore, ME findings correlated significantly with calprotectin (r = 0.50, p = 0.0002) and lactoferrin (r = 0.46, p = 0.0006) levels and slightly with hemoglobin (r = 0.28, p = 0.043) levels. Moreover, each cutoff level of fecal calprotectin, lactoferrin, or hemoglobin had a high sensitivity and specificity for the detection of MES = 0, UCEIS = 0, ME = A, for predicting mucosa healing. Key Messages: Fecal markers correlated not only with MES but also with UCEIS and ME and should be useful for monitoring patients with UC in clinical remission.
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Affiliation(s)
- Shoichiro Mine
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan
| | - Fuminao Takeshima
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan
| | - Yuko Akazawa
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan
| | - Kayoko Matsushima
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan
| | - Hitomi Minami
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan
| | - Naoyuki Yamaguchi
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan
| | - Ken Ohnita
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan
| | - Hajime Isomoto
- Division of Medicine and Clinical Science, Tottori University Faculty of Medicine, Tottori, Japan
| | - Kazuhiko Nakao
- Department of Gastroenterology and Hepatology, Graduate School of Biomedical Science, Nagasaki University, Nagasaki, Japan
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Kato S, Ishibashi A, Kani K, Yakabi K. Optimized Management of Ulcerative Proctitis: When and How to Use Mesalazine Suppository. Digestion 2018; 97:59-63. [PMID: 29393142 DOI: 10.1159/000484224] [Citation(s) in RCA: 15] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
BACKGROUND Ulcerative proctitis, one of the disease types of ulcerative colitis, is considered one of the initial manifestations of ulcerative colitis. Prevention of aggravation of ulcerative proctitis is important for improving the prognosis of ulcerative colitis. Here we reviewed the epidemiology, diagnosis, and management of ulcerative proctitis. SUMMARY The number of patients with ulcerative proctitis is increasing. Disease extension occurs in many patients with ulcerative proctitis. Differential diagnosis from other chronic proctitis is important and should be performed based on the clinical history and endoscopical and histological features. Mesalazine suppository has been the first-line therapy for patients with ulcerative proctitis because of its high effectiveness and safety. Topical treatment of ulcerative proctitis, particularly using mesalazine suppository has been underused in clinical practice. Key Messages: Mesalazine suppositories are more effective than dose intensification of oral mesalazine for relapsed patients with maintenance dose of oral mesalazine. However, low adherence to rectal mesalazine has hindered remission in patients with ulcerative proctitis.
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18
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Nonmelanoma Skin Cancer Risk in Patients With Inflammatory Bowel Disease Undergoing Thiopurine Therapy: A Systematic Review of the Literature. Dermatol Surg 2018; 44:469-480. [PMID: 29315147 DOI: 10.1097/dss.0000000000001455] [Citation(s) in RCA: 33] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Azathioprine and 6-mercaptopurine (thiopurines) are common adjunct treatments for inflammatory bowel disease (IBD). Although thiopurine therapy in organ transplant recipients is known to increase nonmelanoma skin cancers (NMSCs), dermatologic literature yields less data regarding NMSC risk of thiopurine use in IBD. OBJECTIVE The aim of this study was to systematically review current literature on NMSC risk in patients with IBD using thiopurine therapy. METHODS Systematic review of PubMed was performed with keywords "inflammatory bowel disease," "ulcerative colitis," "Crohn's disease," "thiopurine," "azathioprine," "6-mercaptopurine," "skin cancer," "non-melanoma," "squamous cell carcinoma," and "basal cell carcinoma." All available publication years were included. Publications were evaluated using PRISMA guidelines. RESULTS The systematic review yielded 67 articles; 18 met final inclusion criteria. LIMITATIONS Heterogeneity of study designs limited direct comparisons of thiopurine exposure and NMSC risk. CONCLUSION Patients with IBD using thiopurines seem to have a moderately increased risk of NMSC that is proportional to therapy duration. Risk of NMSC seems to decrease or return to baseline after discontinuing therapy, although additional data are needed to support this trend. Younger patients with IBD using thiopurines seem to be at greater risk of NMSC. Appreciating NMSC risk in patients with IBD undergoing thiopurine therapy should help direct skin cancer screening recommendations and sun protective measures.
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19
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Labinac-Peteh L, Terlević R, Krušlin B. Pleomorphic undifferentiated soft tissue sarcoma in patient with long standing inflammatory bowel disease. Autops Case Rep 2018; 8:e2018018. [PMID: 29780754 PMCID: PMC5953184 DOI: 10.4322/acr.2018.018] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2018] [Accepted: 03/06/2018] [Indexed: 12/18/2022]
Abstract
Inflammatory bowel disease (IBD) has been associated with the development of both gastrointestinal and extraintestinal malignancy. The role of therapy in the development of malignancy in IBD has been controversial. We present the case of a 40-year-old female patient with long-standing mild IBD, who developed an undifferentiated pleomorphic sarcoma of the inguinal region and provide a brief review of the relevant literature. While our case likely represents a coincidence of two unrelated pathological entities, clinicians should keep in mind the possibility of soft tissue sarcomas in patients chronically treated with anti-inflammatory agents.
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Affiliation(s)
| | - Robert Terlević
- General Hospital Pula,
Department of Pathology
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Pula
,
Croatia
| | - Božo Krušlin
- University Hospital Center “Sestre milosrdnice”,
Department of Pathology
.
Zagreb
,
Croatia
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20
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Baker KT, Salk JJ, Brentnall TA, Risques RA. Precancer in ulcerative colitis: the role of the field effect and its clinical implications. Carcinogenesis 2018; 39:11-20. [PMID: 29087436 PMCID: PMC6248676 DOI: 10.1093/carcin/bgx117] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/11/2017] [Revised: 09/22/2017] [Accepted: 10/26/2017] [Indexed: 12/13/2022] Open
Abstract
Cumulative evidence indicates that a significant proportion of cancer evolution may occur before the development of histological abnormalities. While recent improvements in DNA sequencing technology have begun to reveal the presence of these early preneoplastic clones, the concept of 'premalignant field' was already introduced by Slaughter more than half a century ago. Also referred to as 'field effect', 'field defect' or 'field cancerization', these terms describe the phenomenon by which molecular alterations develop in normal-appearing tissue and expand to form premalignant patches with the potential to progress to dysplasia and cancer. Field effects have been well-characterized in ulcerative colitis, an inflammatory bowel disease that increases the risk of colorectal cancer. The study of the molecular alterations that define these fields is informative of mechanisms of tumor initiation and progression and has provided potential targets for early cancer detection. Herein, we summarize the current knowledge about the molecular alterations that comprise the field effect in ulcerative colitis and the clinical utility of these fields for cancer screening and prevention.
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Affiliation(s)
- Kathryn T Baker
- Department of Pathology, University of Washington, Seattle, WA, USA
| | - Jesse J Salk
- Division of Hematology and Oncology, Department of Medicine, University of
Washington, Seattle, WA, USA
- TwinStrand Biosciences Seattle, WA, USA
| | - Teresa A Brentnall
- Division of Gasteroenterology, Department of Medicine, University of
Washington, Seattle, WA, USA
| | - Rosa Ana Risques
- To whom correspondence should be addressed. Tel: +206-616-4976; Fax:
+206-543-1140;
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21
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Bye WA, Jairath V, Travis SPL. Editorial: gut selective immunosuppression-is it a double edged sword? Authors' reply. Aliment Pharmacol Ther 2017; 46:374. [PMID: 28677283 DOI: 10.1111/apt.14166] [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: 12/08/2022]
Affiliation(s)
- W A Bye
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
| | - V Jairath
- Departments of Medicine, Epidemiology and Biostatistics, Western University, London, ON, Canada
| | - S P L Travis
- Translational Gastroenterology Unit, John Radcliffe Hospital, Oxford, UK
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