Skin Cancer in Heart Transplant Recipients : Risk Factor Analysis and Relevance of Immunosuppressive Therapy

Immunosuppressive therapies allow long-term patient and transplant survival, but are associated with increased development of UV-induced skin cancers, particularly squamous cell carcinomas. The mechanisms by which CsA, MMF, tacrolimus (TAC) or sirolimus (SRL), alone or in dual combinations, influence tumor development and progression are not completely understood. In the current study, chronically UV-exposed mice treated with SRL alone or in combination with CsA or TAC developed more tumors than mice treated with vehicle or other immunosuppressants, but the tumors were significantly smaller and less advanced. Mice treated with CsA or TAC developed significantly larger tumors than vehicle-treated mice, and a larger percentage in the CsA group were malignant. The addition of MMF to CsA, but not to TAC, significantly reduced tumor size. Immunosuppressant effects on UVB-induced inflammation and tumor angiogenesis may explain these findings. CsA enhanced both UVBinduced inflammation and tumor blood vessel density, while MMF reduced inflammation. Addition of MMF to CsA reduced tumor size and vascularity. SRL did not affect inflammation, but significantly reduced tumor vascularity. Thus the choice of immunosuppressants has important implications for tumor number, size and progression, likely due to the influence of immunosuppressants on UVB-induced inflammation and angiogenesis. † These authors contributed equally to this work.

Section: Introductionmentioning

confidence: 99%

Clinically Relevant Immunosuppressants Influence UVB-Induced Tumor Size Through Effects on Inflammation and Angiogenesis

Duncan¹,

Wulff²,

Tober³

et al. 2007

“…Postoperatively, the majority (83%) of patients had received antilymphocyte and/or antithymocite globulin for 3-5 days. Our immunosuppression protocol consisted of standard cyclosporin A (CsA), azathioprine (Aza) and steroid therapy as previously detailed (7,8). The CsA daily dose was adjusted based on trough target levels (C 0 ), as well as the patient's renal function (assessed by blood creatinine): 150-400 ng/mL (first 3 months), 150-300 (4-12 months), 100-250 (>12 months).…”

Section: Study Patientsmentioning

confidence: 99%

Coronary Flow Reserve by Contrast-Enhanced Echocardiography: A New Noninvasive Diagnostic Tool for Cardiac Allograft Vasculopathy

Tona

Caforio

Montisci

et al. 2006

Self Cite

Noninvasive tests have proven unsatisfactory in cardiac allograft vasculopathy (CAV) diagnosis. We assessed coronary flow reserve (CFR) by contrastenhanced transthoracic echocardiography (CE-TTE) in heart transplantation (HT). CFR was assessed in the left anterior descending coronary artery in 73 HT recipients (59 male, aged 50 ± 12 years at HT), at 8 ± 4.5 years post-HT. CFR measurements were taken blindly from coronary angiographies. CFR cut points were the standard value of ≤2 and those defined by receiver operating characteristics (ROC) curve analysis. CFR was lower in patients with CAV (2.3 ± 0.7 vs. 3.2 ± 0.5, p < 0.0001). The ≤2 cut point was 100% specific and 38% sensitive. The ≤2.7 cut point, optimal by ROC analysis, was 87% specific and 82% sensitive. Accuracy rose from 71% with the standard ≤2 cut point to 85% with the optimal cut point of ≤2.7. CFR by CE-TTE may offer promise as a novel, easily repeatable and accurate noninvasive tool in CAV detection. However, further longitudinal studies in larger patient cohorts are warranted before widespread adoption can be advocated.

“…Between 35-50% of transplant recipients will develop one or more skin cancers by the tenth year following organ transplantation (3)(4)(5)(6). Keratinocyte (nonmelanoma) skin cancers, especially squamous cell carcinomas (SCC), are most common (1,7,8).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of Sun-Protective Practices of Organ Transplant Recipients

Donovan

Rosen

Shaw

2004

The incidence, morbidity and mortality of skin cancer are markedly increased in organ transplant recipients. Efforts aimed at reducing sun exposure through sun avoidance, sunscreens and sun-protective clothing are the most effective means to reduce the risk of skin cancer. We evaluated the sun-protective behaviors of 205 transplant recipients. Twenty-three percent of transplant patients continued to seek a tan. Thirty percent of patients did not use sunscreens, and of those patients who did, less than 5% were committed to using them daily. Thirty-seven percent of patients frequently wore hats and 39% of patients frequently wore additional clothing to block the sun. When data were stratified according to patient age, gender or skin phototype, we identified preferences for specific sun-protective methods. These data strongly suggest that many transplant recipients do not use adequate sun protection. Further study of strategies to encourage the use of sun protection among transplant patients is needed to reduce the incidence of skin cancer.