Clinical risk factors associated with nonmelanoma skin cancer in renal transplant recipients

Ramsay, Helen M.; Fryer, Anthony A.; Reece, Sarah M.; Smith, Andrew G.; Harden, Paul

doi:10.1053/ajkd.2000.8290

Cited by 218 publications

(183 citation statements)

References 25 publications

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“…10,47 The interaction of steroid therapy and the presence of T CM identified in this study also has implications for the interpretation of previous data that CD8 ϩ T CM are markers of tolerance. In the study by Brouard and colleagues, 48 the immune phenotype of tolerant KTRs was compared with KTRs with chronic rejection (n ϭ 14).…”

Section: Cd28mentioning

confidence: 62%

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Immune Phenotype Predicts Risk for Posttransplantation Squamous Cell Carcinoma

Carroll

Segundo²,

Hollowood³

et al. 2010

Journal of the American Society of Nephrology

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Cutaneous squamous cell cancer (SCC) affects up to 30% of kidney transplant recipients (KTRs) within 10 years of transplantation. There are no reliable clinical tests that predict those who will develop multiple skin cancers. High numbers of regulatory T cells associate with poor prognosis for patients with cancer in the general population, suggesting their potential as a predictive marker of cutaneous SCC in KTRs. We matched KTRs with (n ϭ 65) and without (n ϭ 51) cutaneous SCC for gender, age, and duration of immunosuppression and assessed several risk factors for incident SCC during a median follow-up of 340 days. Greater than 35 peripheral FOXP3 ϩ CD4 ϩ CD127 low regulatory T cells/l, Ͻ100 natural killer cells/l, and previous SCC each significantly associated with increased risk for new cutaneous SCC development (hazard ratio [HR] 2.48 [95% confidence interval (CI) 1.04 to 5.98], HR 5.6 [95% CI 1.31 to 24], and HR 1.33 [95% CI 1.15 to 1.53], respectively). In addition, the ratio of CD8/FOXP3 expression was significantly lower in cutaneous SCC excised from KTRs (n ϭ 25) compared with matched SCC from non-KTRs (n ϭ 25) and associated with development of new cutaneous SCCs. In summary, monitoring components of the immune system can predict development of cutaneous SCC among KTRs.

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Section: Cd28mentioning

confidence: 62%

“…9 Age at transplantation and duration and dosage of immunosuppression are major determinants of SCC development. 10,11 Furthermore, dosage of immunosuppression is a major determinant of the risk for SCC metastasis, which has an incidence of 1 to 4%. 9,12 The median survival after a diagnosis of poor-prognosis SCC is approximately 2 years.…”

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confidence: 99%

Immune Phenotype Predicts Risk for Posttransplantation Squamous Cell Carcinoma

Carroll

Segundo²,

Hollowood³

et al. 2010

Journal of the American Society of Nephrology

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“…12, 22 McGregor et a123 suggested that immunosuppressive medications may induce carcinogenesis by selecting defective postreplicative DNA repair clones. Many studies have concluded that the risk of skin cancer is related to the immunosuppressive load, rather than the particular agent,3>' 1, 16,19,21 and that long-term immunosuppression may disrupt normal immunosurveillance with a subsequent proliferation of abnormal cells. 24 However, most studies in renal and heart transplant recipients have not found an increased incidence of skin cancers in patients receiving additional immunosuppression in the form of rejection treatment or induction with ALA or pulse ~t e r o i d s ,~,~5 >~5 and our data confirm these findings.…”

Section: Discussionmentioning

confidence: 99%

Risk factors associated with the development of skin cancer after liver transplantation

Mithoefer

Supran

Freeman

2002

Liver Transplantation

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Skin cancer is a well-recognized long-term complication of transplantation and immunosuppression. Although risk factors for the development of skin cancer in the general population are well defined, risk factors for the development of these lesions have not been identified clearly in the liver transplant population. We surveyed 151 liver transplant (LTx) recipients for risk factors associated with cutaneous malignancies in the general population. Variables included were: demographics, primary liver disease, severity of disease at LTx, immunosuppression history, complexion, hair color, eye color, tanning profile, number of moles, occupational history, sun exposure history, sunburn history, family history of skin cancer, and any history of removed skin lesions. All skin cancers were confirmed histologically. There were 86 documented skin cancers in 34 patients: 56 squamous cell, 23 basal cell and 7 melanomas. Median follow-up was 1490 days. In a univariate analysis, age, male gender, red hair, brown eyes, primary sclerosing cholangitis (PSC), primary biliary cirrhosis (protective), cyclosporine, number of second degree sunburns, and frequent lifetime sun exposure were associated with the development of new skin cancers. In a multivariate model, age, male gender, red hair, brown eyes, PSC, and cyclosporine remain the strongest predictors. The incidence of skin cancer after liver transplantation is underestimated. In particular, there is a higher incidence of squamous cell carcinoma compared with the general population. Recipients with identified risk factors may be candidates for prophylactic treatment and should be followed more intensively after liver transplantation. (Liver TranspZ2002;8:939-944.) T he incide,nce of skin cancer in the general population continues to rise, with more than 1.3 million cases of nonmelanoma skin cancer expected to occur in the United States alone this year.l Risk factors for skin cancer in the general population are well known and include exposure to ultraviolet radiation, sun exposure during childhood, a history of second degree sunburns, the tendency to sunburn easily, fair complexion, blonde or red hair, blue or hazel eyes, occupational exposure, and outdoor Skin cancer is the most common malignancy occurring after solid organ transplantation, with the incidence as high as 35% to 70% at 20 years in parts of the world in which sun exposure is more common.3 The incidence after liver transplantation (LTx) specifically has been reported at 1.6% to 2.2?40415 in two studies with a mean follow-up ranging between 35 and 77.8 months, but there are few published reports, and the length of follow-up in these studies is limited compared with the extensive longterm data in renal transplant patients. In addition, these studies often rely on retrospectively collected singlecenter data or composite registry data, information that patients may not provide spontaneously without specific direct questioning. Although skin cancer is a wellrecognized long-term complication of transplantation and immuno...

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“…(19,26,27,28 (31). On the other hand it is also clear that cyclosporine-treated patients have the same risk of developing NMSC (5,32,33), leading to the conclusion that duration and intensity of the immunosuppression and not specific immunosuppressive agents are the main risk factors for the development of NMSC (6,34,35,36 …”

Section: Nonmelanoma Skin Cancer Is One Of the Most Common Long-term mentioning

confidence: 99%

Switch to a Sirolimus‐Based Immunosuppression in Long‐Term Renal Transplant Recipients: Reduced Rate of (Pre‐)Malignancies and Nonmelanoma Skin Cancer in a Prospective, Randomized, Assessor‐Blinded, Controlled Clinical Trial

Salgo¹,

Goßmann

Schöfer³

et al. 2010

American Journal of Transplantation

202

138

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Renal transplant recipients (RTR) have a 50-200-fold higher risk for nonmelanoma-skin cancer (NMSC) causing high rates of morbidity and sometimes mortality. Cohort-studies gave evidence that a sirolimusbased immunosuppression may inhibit skin tumor growth. This single-center, prospective, assessorblinded, randomized trial investigated if switching to sirolimus treatment inhibits the progression of premalignancies and moreover how many new NMSC occur compared to continuation of the original immunosuppressive therapy. Forty-four RTR (mean age 59.9 years, mean duration of immunosuppression 229.5 months) with skin lesions were randomized to sirolimus or continuation of their original immunosuppression. Blinded dermatological assessment at month 6 and 12 by the same dermatologist evaluated the clinical change compared to baseline. Biopsy was performed in suspected malignancy. Already the 6-month-assessment showed significant superiority of sirolimus-therapy: a stop of progression, even regression of preexisting premalignancies (p < 0.0005). This effect was increased at month 12 (p < 0.0001). Nine patients developed histologically confirmed NMSC: one in the sirolimus group, eight in the control group, p = 0.0176. Sirolimus-based immunosuppression in RTR, even when established many years after transplantation, can delay the development of premalignancies, induce regression of preexisting lesions and decelerate the incidence of new NMSC.

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Clinical risk factors associated with nonmelanoma skin cancer in renal transplant recipients

Cited by 218 publications

References 25 publications

Immune Phenotype Predicts Risk for Posttransplantation Squamous Cell Carcinoma

Immune Phenotype Predicts Risk for Posttransplantation Squamous Cell Carcinoma

Risk factors associated with the development of skin cancer after liver transplantation

Switch to a Sirolimus‐Based Immunosuppression in Long‐Term Renal Transplant Recipients: Reduced Rate of (Pre‐)Malignancies and Nonmelanoma Skin Cancer in a Prospective, Randomized, Assessor‐Blinded, Controlled Clinical Trial

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