Incidence of lymphomas in inflammatory bowel disease: report of an emblematic case, systematic review, and meta-analysis

IntroductionOver 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...

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Main Authors: Maria Francesca Russo, Annalisa Diddoro, Alessandra Iodice, Carola Severi, Lidia Castagneto-Gissey, Giovanni Casella
Format: Article
Language:English
Published: Frontiers Media S.A. 2023-05-01
Series:Frontiers in Medicine
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Online Access:https://www.frontiersin.org/articles/10.3389/fmed.2023.1172634/full
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author Maria Francesca Russo
Annalisa Diddoro
Alessandra Iodice
Carola Severi
Lidia Castagneto-Gissey
Giovanni Casella
author_facet Maria Francesca Russo
Annalisa Diddoro
Alessandra Iodice
Carola Severi
Lidia Castagneto-Gissey
Giovanni Casella
author_sort Maria Francesca Russo
collection DOAJ
description IntroductionOver 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.MethodsStudies 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).ResultsA 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).ConclusionsThe 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 registrationIdentifier: CRD42023398348.
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spelling doaj.art-26d057df911345a1836c7c9c5d8754c22023-05-03T05:07:17ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2023-05-011010.3389/fmed.2023.11726341172634Incidence of lymphomas in inflammatory bowel disease: report of an emblematic case, systematic review, and meta-analysisMaria Francesca Russo0Annalisa Diddoro1Alessandra Iodice2Carola Severi3Lidia Castagneto-Gissey4Giovanni Casella5Department of Surgery, Sapienza University of Rome, Rome, ItalyDepartment of Surgery, Sapienza University of Rome, Rome, ItalyDepartment of Surgery, Sapienza University of Rome, Rome, ItalyDepartment of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, ItalyDepartment of Surgery, Sapienza University of Rome, Rome, ItalyDepartment of Surgery, Sapienza University of Rome, Rome, ItalyIntroductionOver 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.MethodsStudies 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).ResultsA 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).ConclusionsThe 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 registrationIdentifier: CRD42023398348.https://www.frontiersin.org/articles/10.3389/fmed.2023.1172634/fulllymphomainflammatory bowel diseaseulcerative colitisproctocolectomybiologic agents
spellingShingle Maria Francesca Russo
Annalisa Diddoro
Alessandra Iodice
Carola Severi
Lidia Castagneto-Gissey
Giovanni Casella
Incidence of lymphomas in inflammatory bowel disease: report of an emblematic case, systematic review, and meta-analysis
Frontiers in Medicine
lymphoma
inflammatory bowel disease
ulcerative colitis
proctocolectomy
biologic agents
title Incidence of lymphomas in inflammatory bowel disease: report of an emblematic case, systematic review, and meta-analysis
title_full Incidence of lymphomas in inflammatory bowel disease: report of an emblematic case, systematic review, and meta-analysis
title_fullStr Incidence of lymphomas in inflammatory bowel disease: report of an emblematic case, systematic review, and meta-analysis
title_full_unstemmed Incidence of lymphomas in inflammatory bowel disease: report of an emblematic case, systematic review, and meta-analysis
title_short Incidence of lymphomas in inflammatory bowel disease: report of an emblematic case, systematic review, and meta-analysis
title_sort incidence of lymphomas in inflammatory bowel disease report of an emblematic case systematic review and meta analysis
topic lymphoma
inflammatory bowel disease
ulcerative colitis
proctocolectomy
biologic agents
url https://www.frontiersin.org/articles/10.3389/fmed.2023.1172634/full
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