Initial skin cancer screening for solid organ transplant recipients in the United States: Delphi method development of expert consensus guidelines.

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.

Trends of skin cancer mortality after transplantation in the United States: 1987 to 2013.

BACKGROUND: Solid organ transplant recipients are at increased risk of skin cancer, but population-based mortality data are limited. OBJECTIVE: Mortality and predictors of skin cancer death posttransplantation were investigated. METHODS: All US organ transplant recipients between 1987 and 2013, identified through the Organ Procurement and Transplantation Network Standard Transplant Analysis and Research file, were included. Mortality and hazard ratios (HR) were calculated for the overall population and patient subgroups. RESULTS: The overall mortality was 5308 per 100,000 person-years and the skin cancer-specific mortality was 35.27 per 100,000 person-years. Risk factors associated with skin cancer death included thoracic versus abdominal transplantation (HR 2.90, 95% confidence interval [CI] 2.52-3.34), age over 50 years (HR 2.86, CI 2.43-3.38), white race (HR 6.29, CI 4.63-8.53), and male sex (HR 1.85, CI 1.57-2.19). Mortality was highest for malignant melanoma (mortality of 11.48), followed by squamous cell carcinoma (mortality of 4.94) and Merkel cell carcinoma (mortality of 4.59). LIMITATIONS: Limitations of this study included potential underreporting and misclassification of death from skin cancer in the data set. CONCLUSION: Mortality from posttransplantation skin cancer is reported. Older patients, male patients, white patients, and thoracic transplant recipients had increased mortality from skin cancer.

Canonical/ß-catenin Wnt pathway activation improves retinal pigmented epithelium derivation from human embryonic stem cells.

PURPOSE: The purpose of this study was to better understand the role canonical/ß-catenin Wnt signaling plays in the differentiation of human embryonic stem cells (hESCs) into retinal pigmented epithelium (RPE), with the goal of improving methods for derivation. METHODS: Fluorescent reporters were generated to monitor RPE differentiating from hESCs by using a previously described 14-day derivation protocol. Reporters were used to test the effects of the canonical/ß-catenin Wnt pathway agonist CHIR99021 on differentiating RPE. Cells derived from differentiation studies were characterized by lineage-specific transcription factor expression, morphology, pigmentation, and function. The RPE derivation efficiency was determined from percentage positive PMEL17 expression. RESULTS: Fluorescent reporters mimicked expression of endogenous genes during 14-day differentiation to RPE. Analysis of Wnt pathway gene expression showed that the pathway components are expressed in differentiating RPE cells. Addition of CHIR99021 improved RPE derivation based on morphology, expression of RPE-specific lineage markers, and genes involved in melanogenesis. Additionally, expression of the neural retina marker CHX10 was suppressed during differentiation with CHIR99021. Addition of soluble WNT3A, but not WNT5A, had the same result. The CHIR99021-modified protocol yielded cell populations that were 97.77% ± 0.1% positive for the RPE marker PMEL17 at day 14. After cells were expanded to passage 3, they were shown to express RPE markers, carry out phagocytosis of rod outer segments, and secrete pigment epithelium-derived factor apically and vascular endothelial growth factor basally. CONCLUSIONS: Our findings demonstrated the importance of canonical/ß-catenin Wnt signaling in RPE differentiation and showed that manipulating the pathway significantly improves RPE derivation from hESC.