Investigating sun-damaged skin and actinic keratosis with optical coherence tomography: a pilot study.

Actinic Keratosis (AK) arises from sun-damaged skin and is the first clinical manifestation in the multistep process of skin carcinogenesis to invasive squamous cell carcinoma. Thus, it is an ideal target for chemopreventive efforts. Noninvasive measures of AK severity are needed to assess the efficacy of chemoprevention agents. We performed a pilot study on 20 participants to investigate the OCT appearance of sun-protected skin of the upper inner arm as well as sun-damaged skin and early AKs of the dorsal forearms, and to determine if features or quantitative measures in Optical Coherence Tomography (OCT) images could be used to reliably differentiate between these categories. OCT images of upper inner arm (normal appearing skin) showed skin layers and features (stratum corneum, epidermis, dermis, blood vessels) seen in previous studies; additionally in this participant group the subcutaneous fat layer was usually identified. Sun-damaged skin was characterized by increased signal in the epidermis and rapid attenuation of light. AKs were diverse in appearance but frequently characterized by high surface reflection, the presence of a low-signal band in the stratum corneum, and heterogeneous appearance in the epidermis/dermis. Significant differences were found between skin categories using measures of stratum corneum and epidermal/dermal depths and intensities. The presence of a dark band in the stratum corneum was 79% sensitive and 100% specific for AK. This study indicates that OCT holds promise as a useful technique for identifying and characterizing AKs and monitoring their response to chemoprevention agents.

Chemoprevention of human actinic keratoses by topical 2-(difluoromethyl)-dl-ornithine.

Alpha-2-(Difluoromethyl)-dl-ornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, has been shown to suppress skin carcinogenesis in murine models after oral or topical administration. We designed a randomized, placebo-controlled study using a topical hydrophilic ointment formulation with or without 10% (w/w) DFMO. Forty-eight participants with moderate-severe actinic keratoses (AKs) on their forearms (i.e., at least 10 well-circumscribed lesions on the lateral surface) completed a 1-month run-in on placebo ointment. Before randomization, all lateral forearm AKs were circled, counted, photographed, and skin biopsies were obtained for DFMO and polyamine levels. Then participants were randomized to receive DFMO ointment on the right versus the left forearm and placebo hydrophilic ointment on the contralateral forearm twice daily for 6 months. DFMO was not detected in the blood of any subject, and there were no systemic toxicities. None of a subsample of 17 placebo forearms had measurable concentrations of DFMO, whereas 13 of the corresponding DFMO-treated forearms had high DFMO skin levels. As compared with placebo, the 6-month DFMO treatment caused a 23.5% reduction in the number of AKs (P = 0.001) as well as significant suppression of AK biopsy spermidine levels (26%; P = 0.04). Seven of the 48 (14.6%) participants experienced severe (2; 4.2%) or moderate (5; 10.4%) inflammatory reactions on their DFMO-treated arms which required dosing modification. Topical DFMO for 6 months can reduce the number of AK lesions and skin spermidine concentrations in high-risk participants and deserves additional study as a skin cancer chemopreventive agent.

A prospective study of early pregnancy loss.

The New York State Early Pregnancy Detection Study was a prospective study of early pregnancy loss, between implantation and menses, in 217 women attempting to become pregnant during 1989-1992. Women collected urine samples on three consecutive mornings during the late luteal phase of their menstrual cycle, for up to 12 cycles, contributing samples for 1253 menstrual cycles. Urinary human chorionic gonadotrophin (HCG), measured using an immunoradiometric assay, was the biomarker for pregnancy. We observed a range of early pregnancy loss (EPL) rates, from a low estimate of 11.0% to a high estimate of 26.9%, depending on the definition used and the subgroup analysed. Based on a definition of 3 days of HCG concentration > or = 4.00 pmol/l, 2 days > or = 5.33 pmol/l or the last day of HCG > or = 6.67 pmol/l, we identified 115 positive cycles; 95 cycles were clinically confirmed pregnancies and 20 cycles were EPL, giving an EPL rate of 17.4% [95% confidence interval (CI) 11.0-25.6]. In addition, we observed an EPL rate of 19.5% (95% CI 11.3-30.1) for samples collected within a 15 day window around menses, and a rate of 20.3% (95% CI 11.3-32.2) for samples limited to the first three menstrual cycles. Because studies use urine collection schemes other than daily sampling, the definition of pregnancy will be crucial in defining EPL.

An epidemiologic study of Pap screening histories in women with invasive carcinomas of the uterine cervix.

The present study was designed to determine the Pap screening histories of 261 women, ages 20 through 69 years, who were diagnosed with an invasive carcinoma of the uterine cervix. Women who were residents of New York State, exclusive of New York City, and who received a diagnosis between July 1983 and September 1985, were selected for this study. Fifty-four percent of the patients had not received at least one Pap test within three years prior to diagnosis. Women who had not received a prior Pap smear tended to be older, less sexually active, less well educated, and to have more extensive disease at the time of diagnosis than women who had received cytologic examinations. The present study results, coupled to findings of previous reports, demonstrate the need for an intensified effort to insure that all women have access to quality Pap screening services. Particular emphasis needs to be placed on reaching older women who are less likely than younger ones to receive periodic Pap screening. Physicians need to routinely offer older patients who present with nongynecologic conditions the opportunity of receiving cytologic testing.