Faculty Bibliography

Early detection of malignant melanoma remains the key factor in lowering mortality from this cancer. Recognizing the importance of this issue 25 years ago, our group at New York University published in CA: A Cancer Journal for Clinicians the mnemonic 'ABCD' to facilitate the early diagnosis of melanoma. Studies have demonstrated the usefulness of this paradigm in enhancing early melanoma diagnosis as a part of clinical examinations, mass screenings, and public education programs. Approaches to melanoma diagnosis have dynamically evolved during the ensuing quarter century. In the 1990s, dermoscopy enabled the recognition of new subsurface features to differentiate between malignant and benign pigmented lesions. During the last decade, new computer-based technologies have improved diagnostic sensitivity and specificity and may result in optimizing lesion selection for biopsy and pathology review. Despite all of the advances in melanoma diagnosis, timely recognition, detection, and rapid treatment of melanoma remain critical. Although pathologic examination remains the gold standard for diagnosis, this cancer has the potential to be diagnosed through noninvasive approaches because of its cutaneous location. From the development of the ABCDs through current attempts that use complex computer algorithms and genetic markers, a clinician's ability to detect melanoma in its earliest form has been augmented. However, a 'good clinical eye' is still fundamental to selecting the lesions for evaluation among the sea of those that are prevalent. As current approaches are refined and new techniques are developed, the improved ability to diagnose this cancer will hopefully enhance reaching the goal of reducing melanoma mortality

BACKGROUND: The approved imiquimod 5% cream regimen for treating actinic keratoses requires a long treatment time and is limited to a small area of skin. OBJECTIVE: We sought to evaluate imiquimod 2.5% and 3.75% for short-course treatment of the full face or balding scalp. METHODS: In two identical studies, adults with 5 to 20 lesions were randomized to placebo, imiquimod 2.5%, or imiquimod 3.75% (1:1:1). Up to two packets (250 mg each) were applied per dose once daily for two 2-week treatment cycles, with a 2-week, no-treatment interval between cycles. Efficacy was assessed at 8 weeks posttreatment. RESULTS: A total of 479 patients were randomized to placebo, or imiquimod 2.5% or 3.75%. Complete and partial clearance (>/=75% lesion reduction) rates were 6.3% and 22.6% for placebo, 30.6% and 48.1% for imiquimod 2.5%, and 35.6% and 59.4% for imiquimod 3.75%, respectively (P < .001 vs placebo, each; P = .047, 3.75% vs 2.5% for partial clearance). Median reductions from baseline in lesion counts were 25.0% for placebo, 71.8% for imiquimod 2.5%, and 81.8% for imiquimod 3.75% (P < .001, each active vs placebo; P = .048 3.75% vs 2.5%). There were few treatment-related discontinuations. Patient rest period rates were 0% for placebo, 6.9% for imiquimod 2.5%, and 10.6% for imiquimod 3.75%. LIMITATIONS: Local pharmacologic effects of imiquimod, including erythema, may have limited concealment of treatment assignment in some patients. CONCLUSIONS: Both imiquimod 2.5% and 3.75% creams were more effective than placebo and were well tolerated when administered daily as a 2-week on/off/on regimen to treat actinic keratoses

Malignant melanoma represents a significant and growing public health burden in the US and worldwide. It is estimated that 68, 130 cases of invasive malignant melanoma and at least 48,000 cases of melanoma in-situ will be diagnosed in the US this year. Melanoma is also one of the few remaining cancers with increasing US incidence. In the 1930s, the lifetime risk of an American developing invasive malignant melanoma was 1 in 1,500. Currently, that risk is 1 in 59. Deaths from malignant melanoma are also increasing. The mortality rate from malignant melanoma has risen about 2% annually since 1960. This year, it is estimated that 8,700 Americans will die from this cancer. The identification of individuals at high risk for malignant melanoma is important for the development of focused and efficient prevention efforts. Acute sun exposure resulting in sunburn remains a significant risk factor for the development of melanoma, but numerous other potential risk factors have been cited. Included among these are atypical mole syndrome/dysplastic nevus syndrome, blistering sunburns, immunosuppression, prior therapy with psoralen with ultraviolet A light (UVA) light, UV exposure at tanning salons, elevated socioeconomic status, and history of melanoma in a first-degree relative. With a better understanding of the reasons for the increasing rate of this cancer, and with enhanced early detection approaches, we may be able to decrease the incidence and mortality of malignant melanoma

OBJECTIVE:To evaluate the long-term effects of treatment with diclofenac sodium 3% in 2.5% hyaluronic acid gel on clinically diagnosed actinic keratosis lesions in well-defined skin areas. DESIGN/METHODS:A one-year extension of a Phase 4, single-arm, multicenter, open-label study was conducted. Patients in the original study received diclofenac sodium 3% gel twice daily for 90 days. The extension study consisted of a single evaluation approximately one year post-treatment. SETTING/METHODS:Five US centers. PARTICIPANTS/METHODS:Patients who had completed the initial treatment phase with no further treatment for actinic keratosis in the designated treatment blocks. MEASUREMENTS/METHODS:The primary endpoint was the proportion of patients achieving 75-percent clearance of actinic keratosis lesions at one-year follow up based on percent change from baseline in target lesion number score or cumulative lesion number score. Secondary endpoints were the proportion of patients achieving 100-percent actinic keratosis lesion clearance and change in investigator's global improvement index scores. RESULTS:Eighty-one percent of patients reported no additional treatment for actinic keratosis lesions for one year after completing treatment with diclofenac sodium 3% gel. The proportion of patients with 75-percent clearance after one year was 91 percent (95% CI, 84-99%) for target lesions and 70 percent (95% CI, 57-83%) for cumulative lesions. The proportion of patients with 100-percent clearance at one year was 79 percent (95% CI, 67-90%) for target lesions and 30 percent (95% CI, 17-43%) for cumulative lesions. Investigator's global improvement index severity scores showed that the majority (96%) of patients improved from baseline after one year. CONCLUSION/CONCLUSIONS:The efficacy of a single, 90-day course of diclofenac sodium 3% gel persisted in the majority of patients at one year. (J Clin Aesthetic Dermatol. 2009;2(7):20-25.).

Approximately 5% to 10% of melanoma may be hereditary in nature, and about 2% of melanoma can be specifically attributed to pathogenic germline mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A). To appropriately identify the small proportion of patients who benefit most from referral to a genetics specialist for consideration of genetic testing for CDKN2A, we have reviewed available published studies of CDKN2A mutation analysis in cohorts with invasive, cutaneous melanoma and found variability in the rate of CDKN2A mutations based on geography, ethnicity, and the type of study and eligibility criteria used. Except in regions of high melanoma incidence, such as Australia, we found higher rates of CDKN2A positivity in individuals with 3 or more primary invasive melanomas and/or families with at least one invasive melanoma and two or more other diagnoses of invasive melanoma and/or pancreatic cancer among first- or second-degree relatives on the same side of the family. The work summarized in this review should help identify individuals who are appropriate candidates for referral for genetic consultation and possible testing

The use of natural products for skin care has become more common in the past few years. Consumers are more aware of unnatural chemicals and other toxins and are searching for natural products to use on their skin. Fortunately, a large number of botanical antioxidants exist and are being marketed as either over-the-counter or prescription skin care products. Antioxidants can have profound effects on the intracellular signaling pathways involved in skin damage and thus may be protective against photodamage as well as may prevent wrinkles and inflammation. This supplement discusses the potent effect that botanical antioxidants may have in the management of a broad range of skin issues, from photoaging to inflammatory skin conditions.

OBJECTIVE: To determine the utility of the current diameter criterion of larger than 6 mm of the ABCDE acronym for the early diagnosis of cutaneous melanoma. DESIGN: Cohort study. SETTING: Dermatology hospital-based clinics and community practice offices. Patients A total of 1323 patients undergoing skin biopsies of 1657 pigmented lesions suggestive of melanoma. MAIN OUTCOME MEASURE: The maximum lesion dimension (diameter) of each skin lesion was calculated before biopsy using a novel computerized skin imaging system. RESULTS: Of 1657 biopsied lesions, 853 (51.5%) were 6 mm or smaller in diameter. Invasive melanomas were diagnosed in 13 of 853 lesions (1.5%) that were 6 mm or smaller in diameter and in 41 of 804 lesions (5.1%) that were larger than 6 mm in diameter. In situ melanomas were diagnosed in 22 of 853 lesions (2.6%) that were 6 mm or smaller in diameter and in 62 of 804 lesions (7.7%) that were larger than 6 mm in diameter. Conclusion The diameter guideline of larger than 6 mm provides a useful parameter for physicians and should continue to be used in combination with the A, B, C, and E criteria previously established in the selection of atypical lesions for skin biopsy