Capecitabine to reduce nonmelanoma skin carcinoma burden in solid organ transplant recipients.

BACKGROUND: Solidorgan transplant recipients (SOTRs) are at greater risk of nonmelanoma skin cancer (NMSC) than the general population, in large part because of their immunosuppression. Select individual SOTRs demonstrate a rate of tumor development at the upper end of their cohort. Capecitabine, a prodrug converted in the body to 5-fluorouracil (5-FU), may alter the risk for development of NMSC in an individual SOTR with a high rate of tumor development. OBJECTIVE: To report observations of a series of 10 SOTRs treated with capecitabine as adjuvant prevention for high-incidence NMSC. METHODS: Ten SOTRs were administered cycles of low-dose oral capecitabine (0.5-1.5 g/m(2) per day) for days 1 to 14 of a 21-day treatment cycle. Measurements (skin screenings, laboratory and toxicity monitoring) were performed every 1 to 3 months. Incidence rates of squamous cell carcinoma (SCC) before and during treatment were determined and compared using the Wilcoxon signed-rank test. RESULTS: The average incidence rate (mean ± SD) of SCC before treatment (0.56 ± 0.28 SCCs/month, range 0.17-1.17 SCCs/month) declined to 0.16 ± 0.11 SCCs/month (range 0-0.33 SCCs/month) during the first 12 months of treatment (mean reduction 68 ± 30.0%, range 0-100%, p < .005). Reduction in actinic keratosis was observed. Common side effects included fatigue, nausea, hand-and-foot syndrome, gout, and poor renal function. Seven of 10 participants required dose adjustment, and two of these were discontinued from the study drug because of side effects. LIMITATIONS: Case series design, small observational population. CONCLUSIONS: SOTRs experienced a clinically and statistically significant decline in incident SCCs during treatment with low-dose oral capecitabine, with varying degrees of side effects. Larger randomized trials will determine the dose and efficacy of capecitabine for adjuvant treatment of NMSC in SOTRs.

A randomized controlled trial of fractional laser therapy and dermabrasion for scar resurfacing.

BACKGROUND: Dermabrasion has been the standard resurfacing procedure for postsurgical scars, but recovery can be long. Fractionated carbon dioxide (CO2 ) laser is a safe, effective tissue resurfacing modality, but no prospective trial has compared its safety or efficacy with that of dermabrasion for postsurgical scar resurfacing. OBJECTIVE: To compare the safety and efficacy of single-treatment fractional photothermolysis with that of single-treatment dermabrasion for postsurgical scar resurfacing on the face. METHODS AND MATERIALS: A split-scar method was used to compare fractionated CO2 laser and diamond fraise dermabrasion on postsurgical scars of the face. Primary endpoint was safety at day 0, 1 week, and 1 month. Secondary endpoint was efficacy at 3 months as measured by blinded evaluation of standardized photographs. RESULTS: Safety data revealed that there was less erythema (p = .001) and bleeding (p = .001) at day 0, less erythema (p = .01) and edema (p = .046) at 1 week, and a trend toward less erythema at 1 month (p = .06) with fractionated CO2 . Efficacy data at 3 months revealed equivalent scar improvements (p = .77). CONCLUSION: Fractionated CO2 laser therapy should be considered a safe alternative for surgical scar resurfacing on the face. The safety profile exceeds that of dermabrasion, and it has a quicker clinical recovery and equivalent cosmetic efficacy.

Efficacy of a multiple diode laser system for body contouring.

BACKGROUND AND OBJECTIVES: Low-level laser therapy (LLLT) has been shown to induce cellular reactions in nonphotosynthetic cells however skepticism remains regarding efficacy at the clinical level. The purpose of this study was to evaluate the efficacy of LLLT independent of liposuction. Additionally, a weight loss supplement (Curva™, Santa Barbra Medical Innovations, Santa Barbra, CA) was evaluated. This clinical trial evaluates the effectiveness of the Erchonia EML Laser (Zerona™ System, Santa Barbra Medical Innovations) for non-invasive fat reduction and body contouring in a split-body clinical evaluation. MATERIALS AND METHODS: Five subjects were enrolled and completed the study. Subjects had a body mass index (BMI) of less than or equal to 29 kg/m(2) and satisfied the set inclusion criteria. Participants were randomly assigned to receive low-level laser treatments on one side of the body three times per week for 2 weeks. One group took the weight loss supplement and was also treated with the laser. Subject satisfaction questionnaires, physician blinded photo evaluation, circumference measurements and ultrasound measurements were utilized to evaluate efficacy. RESULTS: Circumference measurements revealed no statistically significant reduction at either 7 days or 1 month post-treatment. One month following treatment the greatest circumference reduction overall was 0.5 ± 0.3 inches. Ultrasound measurements also did not reveal statistically significant reduction in fat layer thickness (P > 0.5). Evaluation by three blinded dermatologists resulted in average correct photo identification of 51.1%. Results reflect little clinical difference between post-treatment and baseline images. Three subjects recording a "dissatisfied" rating on satisfaction questionnaires and all subjects reported the effects of the treatment were less than expected. Subjects who took the weight loss supplement had no greater circumference reduction or identifiable clinical outcome. CONCLUSIONS: This small study demonstrates to the authors that there needs to be more evidence to show clinical circumferential reduction before LLLT can be recommended as an effective therapeutic option.

Capecitabine for skin cancer prevention in solid organ transplant recipients.

Skin cancers are the most common malignancies in solid organ transplant recipients (SOTR). A case-observational, retrospective study was performed to determine the efficacy of low-dose capecitabine in the secondary prevention of skin cancers in SOTRs treated at a single institution. SOTRs with recurrent squamous cell carcinoma (SCC) and/or basal cell carcinoma (BCC) were given low-dose capecitabine 1 g/m(2) daily, days 1-14 of a 21-d treatment cycle. Skin surveillance was performed by dermatologists every 1-3 months. Cumulative incidence rates of SCC, BCC, and actinic keratosis (AK) before and after treatment were scored and statistically compared for each patient using a non-parametric Wilcoxon signed rank test. Fifteen patients (13 men and two women) with a median age of 57 yr (range 40-73) were treated. Incidence rates as measured by mean number of events per month declined by 0.33 for SCC, 0.04 for BCC, and 2.45 for AK (p < 0.05). The most common grade 3 and 4 toxicities included fatigue (40.0%), hand-foot syndrome (20.0%), and diarrhea (20.0%). The discontinuation rate at one yr was approximately 33.3%. We conclude that oral capecitabine significantly decreases the incidence rates of recurrent SCC, BCC, and AK in SOTRs and is associated with manageable toxicity.

Kruppel-like factor 2 regulates thymocyte and T-cell migration.

Mammalian Kruppel-like transcription factors are implicated in regulating terminal differentiation of several tissue types. Deficiency in Kruppel-like factor (KLF) 2 (also known as LKLF) leads to a massive loss of the peripheral T-cell pool, suggesting KLF2 regulates T-cell quiescence and survival. Here we show, however, that KLF2 is essential for T-cell trafficking. KLF2-deficient (Klf2-/-) thymocytes show impaired expression of several receptors required for thymocyte emigration and peripheral trafficking, including the sphingosine-1-phosphate (S1P) receptor S1P1, CD62L and beta7 integrin. Furthermore, KLF2 both binds and transactivates the promoter for S1P1--a receptor that is critical for thymocyte egress and recirculation through peripheral lymphoid organs. Our findings suggest that KLF2 serves to license mature T cells for trafficking from the thymus and recirculation through secondary lymphoid tissues.

Phenotypic analysis of T-cells in extensive alopecia areata scalp suggests partial tolerance.

This study demonstrates the feasibility and efficacy of using flow cytometric analysis with intracellular cytokine staining for characterization of T-cell phenotype and functional status in extensive alopecia areata (EAA) scalp skin. Cell suspensions were made from scalp punch biopsies taken from 12 patients with long-standing EAA (average disease duration 14 years, 95% hair loss) and six control subjects. EAA samples had a lower percentage of CD-3-expressing cells, but CD-4/CD-8 ratios remained similar to controls. Expression of CD-69 was found only in EAA scalp biopsies, suggesting that T-cells from EAA scalp have undergone activation. No difference was found in tumor necrosis factor alpha expression. Surprisingly, EAA scalp T-cells produced less IL-2 and CD-8 T-cells produced less IFN-gamma. Immunohistochemical staining of formalin-fixed paraffin-embedded specimens demonstrated that IFN-gamma-producing cells in EAA scalp were not greater in number than in normal specimens. The few identified IFN-gamma-producing cells demonstrated no tendency to localize to the perifollicular region, and were similarly distributed as in control specimens. The abnormalities in cytokine production may explain the relative paucity of inflammatory change observed in the clinical setting and suggest that T-cell responses in EAA scalp are tightly, albeit aberrantly, regulated via mechanisms of peripheral T-cell tolerance.

Differential role for IL-7 in inducing lung Kruppel-like factor (Kruppel-like factor 2) expression by naive versus activated T cells.

Kruppel-like Factor 2 [KLF2, also called lung Kruppel-like factor (LKLF)] is a transcription factor shown to be necessary for the maintenance of naive T cells. KLF2 is expressed in both naive and memory cells, and is proposed to promote quiescence in these populations. During T cell stimulation, both KLF2 protein and mRNA are down-regulated, and loss of KLF2 appears to be critical for full T cell activation. It is unclear, however, how KLF2 expression is maintained in naive T cells. Recently it was proposed that IL-7, which is known to promote KLF2 re-expression in antigen-stimulated T cells, may also induce KLF2 expression in naive T cells. Here we address this issue by comparing the impact of IL-7 on KLF2 expression in naive and activated T cells. Use of bcl-2 transgenic T cells allowed us to uncouple the requirements for IL-7 in preserving naive T cell survival from its role in maintaining KLF2 expression. Our data demonstrates that IL-7 signals are not required for KLF2 maintenance in naive T cells, suggesting that this cytokine has distinct effects on KLF2 expression in naive versus activated T cells.