Comparative effectiveness of nonpurpuragenic 595-nm pulsed dye laser and microsecond 1064-nm neodymium:yttrium-aluminum-garnet laser for treatment of diffuse facial erythema: A double-blind randomized controlled trial.

BACKGROUND: Facial erythema is a common symptom that responds to vascular laser treatment, but there are few comparative studies. OBJECTIVE: We sought to compare the effectiveness of microsecond 1064-nm neodymium:yttrium-aluminum-garnet (Nd:YAG) laser with nonpurpuragenic 595-nm pulsed dye laser (PDL) for diffuse facial erythema. METHODS: This was a split-face, double-blind randomized controlled trial. Bilateral cheeks received 4 treatments each at one month intervals with PDL or Nd:YAG. Spectrophotometer measurements, digital photographs, pain scores, and patient preferences were recorded. RESULTS: Sixteen patients enrolled and 2 dropped out. Fourteen patients, all skin types I to III, 57% women, mean age 42 years, completed the study and were analyzed. Spectrophotometer readings changed after both PDL (8.9%) and Nd:YAG (2.5%), but varied by treatment type, with PDL reducing facial redness 6.4% more from baseline than Nd:YAG (P = .0199; 95% confidence interval -11.6 to -1.2). Pain varied (P = .0028), with Nd:YAG associated with less pain, at 3.07, than PDL at 3.87. Subjects rated redness as improved by 52% as a result of PDL, and 34% as a result of Nd:YAG (P = .031; 95% confidence interval -34.6 to -1.94). No serious adverse events were observed. LIMITATIONS: Lasers settings are not standardized across devices. CONCLUSION: Facial erythema is safely and effectively treated with PDL and Nd:YAG. Nonpupuragenic PDL may be more effective for lighter-skinned patients, but microsecond Nd:YAG may be less painful.

Flammability of topical preparations and surgical dressings in cutaneous and laser surgery: a controlled simulation study.

BACKGROUND: Surgical fires are a rare, but serious complication of dermatologic procedures involving electrosurgical and laser devices. Given the lack of data regarding basic fire safety principles, many dermatologists remain unaware of this potential risk. OBJECTIVE: We evaluated the flammability of topical preparations and surgical drapes commonly encountered in the immediate operative field during cutaneous and laser surgery. METHODS: Surgical dressings, drapes, and pork belly skin were examined for fire risk upon exposure to isopropyl alcohol, chlorhexidine gluconate, and aluminum chloride under dry, saturated, and damp conditions. Both electrosurgery and a carbon-dioxide laser were used as ignition sources. RESULTS: At least some char was observed in 86 of 126 simulated conditions (68%). Flames occurred in 2 test conditions: dry underpad drapes and cotton balls exposed to the carbon-dioxide laser. In general, drapes and dressings dampened or saturated with isopropyl alcohol failed to ignite with electrofulguration or electrodessication, although sparks and moderate char developed on pork belly skin and the underpad drape. Materials dampened or saturated with chlorhexidine gluconate, which contains isopropyl alcohol, generated less smoke and char compared with materials exposed to aluminum chloride, which does not contain alcohol. LIMITATIONS: Future studies may assess the flammability of materials in the setting of oxygen supplementation. CONCLUSION: In common cutaneous surgical environments, electrosurgery or ablative laser may lead to char and rarely to fire. Char may be seen in up to two thirds of simulated conditions, and in a minute proportion of conditions, fire is observed.

Safety of a novel microneedle device applied to facial skin: a subject- and rater-blinded, sham-controlled, randomized trial.

OBJECTIVE: To assess the safety of a novel microneedle device on facial skin of healthy individuals of all Fitzpatrick skin types. DESIGN: Subject- and live rater­blinded, sham-controlled, randomized trial. SETTING: University-based ambulatory dermatology service providing both primary and referral care. PARTICIPANTS: Healthy adults recruited from postings. INTERVENTION: Device or sham applied with finger pressure to the right or left sides, respectively, of the participants' lateral forehead, temple, and nasolabial fold. At the 24-hour visit, a larger area (3 × 3 matrix) at the central forehead was treated with the device, and the participants applied the device to their chins. MAIN OUTCOME MEASURE: Live blinded rater determination of local skin reaction scores (SRSs). RESULTS: At the 5-minute skin assessment, the median SRS was 1 for all skin type and age groups. There was no median pain score higher than 1 for any age or skin type group. For the sham device, median SRSs were 0 at all time points for all age and skin type groups. Mean SRSs for the device and sham were significantly different only for the lateral forehead at 5 and 30 minutes (P = .04). CONCLUSIONS: The microneedle device appears to be safe and well tolerated in both sexes and various skin types and ages. Facial skin application of the device elicits mild, self-limited, and rapidly resolving erythema marginally greater than that associated with the sham control.

Deep dermatophytosis caused by Trichophyton rubrum.

A 50-year-old man with hepatitis C virus infection and liver cirrhosis, who was awaiting transplantation, was admitted to the Transplant Surgery Service for treatment of a pleural effusion and an elevated ammonia level. Skin examination showed violaceous, firm nodules on the right thigh, which had been present for eight months. A fungal culture showed Trichophyton rubrum. The patient was started on itraconazole with improvement in the eruption.

Do lasers or topicals really work for nonmelanoma skin cancers?

Novel strategies are urgently needed to address the millions of nonmelanoma skin cancers treated in the United States annually. The need is greatest for those patients who are poor surgical candidates or those prone to numerous nonmelanoma skin cancers and therefore at risk for marked disfigurement. Traditional treatment strategies include electrosurgery with curettage, radiation therapy, cryotherapy, excision, and Mohs micrographic surgery. Alternatives to traditional treatment, including topical medications and light or laser therapies, are becoming popular; however, there are various degrees of efficacy among these alternative tactics. These alternatives include topical retinoids, peels, 5-fluorouracil, imiquimod, photodynamic therapy, and lasers. The purpose of this paper is to review the available data regarding these alternative strategies and permit the reader to have a sense of which therapies are reasonable options for care.

Complications of lasers and light treatments.

Cutaneous lasers and lights, and also more novel cutaneous energy modalities like radiofrequency and ultrasound, are in general very safe interventions with an associated rapid healing time. Posttreatment sequelae are usually mild and spontaneously resolving, with erythema and edema lasting hours to days. More troublesome, less common short-term adverse events include urticaria, erosions, crusting, ecchymoses, blistering, and infection. Medium-term adverse events include hyperpigmentation, hypopigmentation, a line of demarcation, burns, textural imperfections, and delayed reepithelialization. Long-term to permanent adverse events, which are fortunately rare, include indentation, scar, and ocular damage. With few exceptions, there are management strategies for avoiding laser adverse events, and, if they do occur, for mitigating their impact.

Familial benign chronic pemphigus (Hailey-Hailey disease).

A 57-year-old woman presented with a 27-year history of vesicles and crusted erosions of the intertriginous folds. Prior treatments had included topical glucocorticoids, mupirocin, and minocycline, all of which provided minimal relief. A skin biopsy specimen was consistent with Hailey-Hailey disease. Hailey-Hailey disease is the result of mutations in the ATP2C1 gene and is characterized by recurrent vesicles and erosions in intertriginous areas. Whereas topical and/or systemic antibiotic/antifungal agents in combination with topical glucocorticoids is the mainstay of treatment, case reports have documented dramatic improvement with oral retinoids, calcitriol, and tacrolimus.

Multiple eruptive milia.

A 61-year-old-man presented with a sudden onset of multiple, hyperpigmented papules with a central punctum on the face, chest, upper back, and arms. Histopathologic examination showed infundibular cysts. These findings are consistent with a diagnosis of multiple eruptive milia, which is a rare disorder that is characterized by the sudden development of crops of milia over weeks to months. They are more extensive in number and distribution than they are in primary milia. Milia may present spontaneously without a known cause, as part of an inherited familial condition, or as part of a genodermatosis. The etiologies are uncertain, and treatment options are varied.

Phosphorylated 4E-BP1 is associated with poor survival in melanoma.

PURPOSE: Both phosphatidylinositol 3-kinase/AKT and RAS/mitogen-activated protein kinase signal transduction pathways mediate 4E-BP1 phosphorylation, releasing 4E-BP1 from the mRNA cap and permitting translation initiation. Given the prevalence of PTEN and BRAF mutations in melanoma, we first examined translation initiation, as measured by phosphorylated 4E-BP1 (p-4E-BP1), in metastatic melanoma tissues and cell lines. We then tested the association between amounts of total and p-4E-BP1 and patient survival. EXPERIMENTAL DESIGN: Seven human metastatic melanoma cells lines and 72 metastatic melanoma patients with accessible metastatic tumor tissues and extended follow-up information were studied. Expression of 4E-BP1 transcript, total 4E-BP1 protein, and p-4E-BP1 was examined. The relationship between 4E-BP1 transcript and protein expression was assessed in a subset of patient tumors (n = 41). The association between total and p-4E-BP1 levels and survival was examined in the larger cohort of patients (n = 72). RESULTS: 4E-BP1 was hyperphosphorylated in 4 of 7 melanoma cell lines harboring both BRAF and PTEN mutations compared with untransformed melanocytes or RAS/RAF/PTEN wild-type melanoma cells. 4E-BP1 transcript correlated with 4E-BP1 total protein levels as measured by the semiquantitative reverse-phase protein array (P = 0.012). High levels of p-4E-BP1 were associated with worse overall and post-recurrence survival (P = 0.02 and 0.0003, respectively). CONCLUSION: Our data show that translation initiation is a common event in human metastatic melanoma and correlates with worse prognosis. Therefore, effective inhibition of the pathways responsible for 4E-BP1 phosphorylation should be considered to improve the treatment outcome of metastatic melanoma patients.

Association of MDM2 SNP309, age of onset, and gender in cutaneous melanoma.

PURPOSE: In certain cancers, MDM2 SNP309 has been associated with early tumor onset in women. In melanoma, incidence rates are higher in women than in men among individuals less than 40 years of age, but among those older than 50 years of age, melanoma is more frequent in men than in women. To investigate this difference, we examined the association among MDM2 SNP309, age at diagnosis, and gender among melanoma patients. EXPERIMENTAL DESIGN: Prospectively enrolled melanoma patients (N = 227) were evaluated for MDM2 SNP309 and the related polymorphism, p53 Arg72Pro. DNA was isolated from patient blood samples, and genotypes were analyzed by PCR-restriction fragment length polymorphism. Associations among MDM2 SNP309, p53 Arg72Pro, age at diagnosis, and clinicopathologic features of melanoma were analyzed. RESULTS: The median age at diagnosis was 13 years earlier among women with a SNP309 GG genotype (46 years) compared with women with TG+TT genotypes (59 years; P = 0.19). Analyses using age dichotomized at each decade indicated that women with a GG genotype had significantly higher risks of being diagnosed with melanoma at ages <50 years compared with women >or=50 years, but not when the comparison was made between women <60 and >or=60 years. At ages <50 years, women with a GG genotype had a 3.89 times greater chance of being diagnosed compared with women with TG+TT genotypes (P = 0.01). Similar observations were not seen among men. CONCLUSIONS: Our data suggest that MDM2 may play an important role in the development of melanoma in women. The MDM2 SNP309 genotype may help identify women at risk of developing melanoma at a young age.

Meta-analysis of sentinel lymph node positivity in thin melanoma (

BACKGROUND: Despite the lack of an established survival benefit of sentinel lymph node (SLN) biopsy, this technique has been increasingly applied in the staging of thin (

The "dysplastic" nevus.

Dysplastic nevi have become an increasing focus clinically, with evidence that they are associated with a higher risk of developing melanoma. However, there still is contention regarding the significance of dysplastic nevi. This contribution provides an overview of the history, epidemiology, genetics, clinical and histologic features, and procedures for clinical management of dysplastic nevi. Since dysplastic nevi were described originally in 1978, a great deal of research has examined the epidemiology of these lesions and the genetic factors related to the development of dysplastic nevi. However, there is disagreement regarding the clinical management of dysplastic nevi and the histologic definition of dysplastic nevi. Current recommendations include preventative measures, such as sun protection and careful surveillance and biopsies of suspicious lesions as needed. The advent of new technologies, such as computer-vision systems, have the potential to significantly change treatment of dysplastic nevi in the future.

Assessing the clinical utility of measuring Insulin-like Growth Factor Binding Proteins in tissues and sera of melanoma patients.

BACKGROUND: Different Insulin-like Growth Factor Binding Proteins (IGFBPs) have been investigated as potential biomarkers in several types of tumors. In this study, we examined both IGFBP-3 and -4 levels in tissues and sera of melanoma patients representing different stages of melanoma progression. METHODS: The study cohort consisted of 132 melanoma patients (primary, n = 72; metastatic, n = 60; 64 Male, 68 Female; Median Age = 56) prospectively enrolled in the New York University School of Medicine Interdisciplinary Melanoma Cooperative Group (NYU IMCG) between August 2002 and December 2006. We assessed tumor-expression and circulating sera levels of IGFBP-3 and -4 using immunohistochemistry and ELISA assays. Correlations with clinicopathologic parameters were examined using Wilcoxon rank-sum tests and Spearman-rank correlation coefficients. RESULTS: Median IGFBP-4 tumor expression was significantly greater in primary versus metastatic patients (70% versus 10%, p = 0.01) A trend for greater median IGFBP-3 sera concentration was observed in metastatic versus primary patients (4.9 microg/ml vs. 3.4 microg/ml, respectively, p = 0.09). However, sera levels fell within a normal range for IGFBP-3. Neither IGFBP-3 nor -4 correlated with survival in this subset of patients. CONCLUSION: Decreased IGFBP-4 tumor expression might be a step in the progression from primary to metastatic melanoma. Our data lend support to a recently-described novel tumor suppressor role of secreting IGFBPs in melanoma. However, data do not support the clinical utility of measuring levels of IGFBP-3 and -4 in sera of melanoma patients.

Changes in the presentation of nodular and superficial spreading melanomas over 35 years.

BACKGROUND: Nodular melanoma (NM) may be biologically aggressive compared with the more common superficial spreading melanoma (SSM), with recent data suggesting underlying genetic differences between these 2 subtypes. To better define the clinical behavior of NMs, the authors compared their clinical and histopathologic features to those of SSMs at their institution, a tertiary referral center, over 3 decades. METHODS: A total of 1,684 patients diagnosed with 1,734 melanomas were prospectively enrolled. Of these, 1,143 patients (69% SSM, 11% NM, 20% other) were diagnosed between 1972 and 1982; 541 patients (54% SSM, 23% NM, 23% other) were diagnosed between 2002 and the present. Differences between the features of NM and SSM within each time period as well as changes over time were analyzed. RESULTS: The authors found that SSMs are now diagnosed as thinner lesions (P < .0001) with a low incidence of histologic ulceration (P < .0001), whereas there was no significant change in the median tumor thickness or ulceration status of NMs over time (P = .10, P = .30, respectively). The median age at diagnosis of NM, however, did significantly increase over time (51 years to 63 years, P < .01). The median duration of NMs was reported to be only 5 months compared with 9 months in SSM patients. CONCLUSIONS: The authors' data suggest that improvements have been made in the early detection of SSM but not NM. Modifications of current screening practices, including increased surveillance of high-risk patients with an emphasis on the "E" for "evolution" criterion of the ABCDE acronym used for early detection of melanoma, are thus warranted.

Shedding of distinct cryptic collagen epitope (HU177) in sera of melanoma patients.

PURPOSE: Extracellular matrix remodeling during tumor growth plays an important role in angiogenesis. Our preclinical data suggest that a newly identified cryptic epitope (HU177) within collagen type IV regulates endothelial and melanoma cell adhesion in vitro and angiogenesis in vivo. In this study, we investigated the clinical relevance of HUI77 shedding in melanoma patient sera. EXPERIMENTAL DESIGN: Serum samples from 291 melanoma patients prospectively enrolled at the New York University Medical Center and 106 control subjects were analyzed for HU177 epitope concentration by a newly developed sandwich ELISA assay. HU177 serum levels were then correlated with clinical and pathologic parameters. RESULTS: Mean HU177 epitope concentration was 5.8 ng/mL (range, 0-139.8 ng/mL). A significant correlation was observed between HU177 concentration and nodular melanoma histologic subtype [nodular, 10.3 +/- 1.6 ng/mL (mean +/- SE); superficial spreading melanoma, 4.5 +/- 1.1 ng/mL; all others, 6.1 +/- 2.1 ng/mL; P = 0.01 by ANOVA test]. Increased HU177 shedding also correlated with tumor thickness (< or =1.00 mm, 3.8 +/- 1.1 ng/mL; 1.01-3.99 mm, 8.7 +/- 1.3 ng/mL; > or =4.00 mm, 10.3 +/- 2.4 ng/mL; P = 0.003 by ANOVA). After multivariate analysis controlling for thickness, the correlation between higher HU177 concentration and nodular subtype remained significant (P = 0.03). The mean HU177 epitope concentration in control subjects was 2.4 ng/mL. CONCLUSIONS: We report that primary melanoma can induce detectable changes in systemic levels of cryptic epitope shedding. Our data also support that nodular melanoma might be biologically distinct compared with superficial spreading type melanoma. As targeted interventions against cryptic collagen epitopes are currently undergoing phase I clinical trial testing, these findings indicate that patients with nodular melanoma may be more susceptible to such targeted therapies.

The diagnostic performance of expert dermoscopists vs a computer-vision system on small-diameter melanomas.

OBJECTIVE: To evaluate the performance of dermoscopists in diagnosing small pigmented skin lesions (diameter