Risk of melanoma and nonmelanoma skin cancer among patients with inflammatory bowel disease.

Department of Medicine, University of North Carolina, Chapel Hill, NC, USA.
Gastroenterology (Impact Factor: 12.82). 05/2012; 143(2):390-399.e1. DOI: 10.1053/j.gastro.2012.05.004
Source: PubMed

ABSTRACT Patients with inflammatory bowel disease (IBD) are at risk for certain malignancies. We aimed to determine the risk of melanoma and nonmelanoma skin cancer (NMSC) in patients with IBD and how medications affect these risks.
We performed retrospective cohort and nested case-control studies using administrative data from the LifeLink Health Plan Claims Database from 1997 to 2009. The cohort comprised 108,579 patients with IBD, and each was matched to 4 individuals without IBD. The risk of melanoma and NMSC was evaluated by incidence rate ratio (IRR) and by adjusted Cox proportional hazard ratio (HR) modeling. In nested case-control studies, patients with melanoma or NMSC were matched to 4 patients with IBD without melanoma or NMSC. Conditional logistic regression was used to determine associations between medications and both skin cancers.
In the cohort, IBD was associated with an increased incidence of melanoma (IRR, 1.29; 95% confidence interval [CI], 1.09-1.53). Risk was greatest among individuals with Crohn's disease (IRR, 1.45; 95% CI, 1.13-1.85; adjusted HR, 1.28; 95% CI, 1.00-1.64). The incidence of NMSC also increased among patients with IBD (IRR, 1.46; 95% CI, 1.40-1.53) and was greatest among those with CD (IRR, 1.64; 95% CI, 1.54-1.74). In the nested case-control studies, therapy with biologics increased the risk of melanoma (odds ratio [OR], 1.88; 95% CI, 1.08-3.29). Patients who had been treated with thiopurines had an increased risk of NMSC (OR, 1.85; 95% CI, 1.66-2.05).
Immunosuppression increases the risk of melanoma and NMSC among patients with IBD. The risk of melanoma is increased by use of biologics, and the risk of NMSC is increased by use of thiopurines. Patients with IBD should be counseled and monitored for skin cancer.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ulcerative colitis can cause debilitating symptoms and complications such as colonic strictures, colonic dysplasia, colorectal cancer, and toxic megacolon or perforation. Goals of treatment in ulcerative colitis include resolution of gastrointestinal symptoms, healing of colonic mucosa, and prevention of disease complications. Our treatment armamentarium has expanded dramatically over the past 10 years, and we now have multiple biologic agents approved for the treatment of moderate-severe disease, in addition to conventional therapies such as 5-aminosalicylates, thiopurines, and corticosteroids. In this review, we will provide a detailed discussion of the three tumor necrosis factor-alpha (TNF-α) inhibitors currently approved for treatment of ulcerative colitis: infliximab, adalimumab, and golimumab. All three agents are effective for inducing and maintaining clinical response and remission in patients with ulcerative colitis, and they have comparable safety profiles. There are no head-to-head trials comparing their efficacy, and the choice of agent is most often based on insurance coverage, route of administration, and patient preference. Combination therapy with an immunomodulator is proven to be more effective than anti-TNF monotherapy, and patients who lose response to an anti-TNF agent should undergo dose intensification in order to regain clinical response. Despite therapeutic optimization, a significant percentage of patients will not achieve clinical remission with anti-TNF agents, and so newer therapies are on the horizon.
    Therapeutics and Clinical Risk Management 01/2015; 11:63-73. · 1.34 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: One of the most effective forms of therapeutic enteral nutrition is designated as "exclusive enteral nutrition" (EEN). EEN constitutes the monotonous enteral delivery of complete liquid nutrition and has been most explored in the treatment Crohn's disease (CD), a form of inflammatory bowel disease. While EEN's mechanisms of action are not clearly understood, it has been shown to modify the composition of the intestinal microbiome, an important component of CD pathogenesis. The current literature on the intestinal microbiome in healthy individuals and CD patients is reviewed with respect to EEN therapy. Further investigations in this field are needed to better understand the role and potential for EEN in chronic human disorders.
    Nutrients 11/2014; 6(11):5298-5311. · 3.15 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Klar E delivered material support and critically revised the manuscript for important intellectual content; Bliemeister A acquired data and performed statistics; Linnebacher M designed and supervised the study, drafted and critically revised the manuscript. Supported by University of Rostock (FORUN program) Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: Abstract AIM: To analyze the cellular immune response towards microsatellite-instability (MSI)-induced frameshift- Reactivity against microsatellite instability-induced frameshift mutations in patients with inflammatory bowel disease peptides (FSPs) in patients suffering from inflammatory bowel disease (IBD) with and without thiopurine-based immunosuppressive treatment. METHODS: Frequencies of peripheral blood T cell responses of IBD patients (n = 75) against FSPs derived from 14 microsatellite-containing candidate genes were quantified by interferon-γ enzyme-linked immunospot. T cells derived from 20 healthy individuals served as controls. RESULTS: Significant T cell reactivities against MSI-induced FSPs were observed in 59 of 75 IBD patients (78.7%). This was significantly more as we could observe in 20 healthy controls (P = 0.001). Overall, the reactivity was significantly influenced by thiopurine treatment (P = 0.032) and duration of disease (P = 0.002) but not by duration or cumulative amount of thiopurine therapy (P = 0.476). Unexpected, 15 of 24 (62.5%) IBD patients without prior thiopurine treatment also showed increased FSP-specific immune responses (P = 0.001). CONCLUSION: These findings propose FSPs as potential novel class of inflammation-associated antigens and this in turn may have implications for screening, diagnosis as well as clinical management of patients suffering from IBD and other inflammatory conditions. Core tip: Oxidative stress resulting from chronic inflammation is likely to relax the mismatch repair (MMR) system and to cause DNA damage. On the other hand thiopurine treatment positively selects for cell variants with defective MMR system. inflammatory bowel disease (IBD) patients are often exposed to both factors, hypothetically resulting in an increased number of frameshift mutations. This study shows an increased immune response towards microsatellite-instability-induced frameshift-peptides (FSPs) in patients with IBD. It is the first report which provides functional evidence of FSP expression under non-but possible pre-neoplastic conditions. These findings have potential implications for screening, diagnosis as well as clinical management of IBD patients. against microsatellite instability-induced frameshift mutations in patients with inflammatory bowel disease. World J Gastroenterol 2015; 21(1): 221-228 Available from:
    World Journal of Gastroenterology 01/2015; 221(7):221-228. · 2.43 Impact Factor