A Highly Verified Assay for KRAS Mutation Detection in Tissue and Plasma of Lung, Colorectal, and Pancreatic Cancer.

CONTEXT.­: KRAS Mutation Test v2 is used for the qualitative detection and identification of 28 mutations in exons 2, 3, and 4 of the human KRAS gene. OBJECTIVE.­: To verify the performance of KRAS Mutation Test v2 and to evaluate its accuracy by correlation with a next-generation sequencing method on Illumina MiSeq. DESIGN.­: In this study, we used formalin-fixed, paraffin-embedded tissue and plasma specimens from non-small cell lung cancer, colorectal cancer, and pancreatic cancer patients. Results of specificity, precision, analytical sensitivity, and accuracy as compared with a MiSeq method are reported. RESULTS.­: The KRAS Mutation Test v2 demonstrated exquisite sensitivity and specificity and broad coverage of KRAS mutations. Precision was 100% (108 of 108) across all samples, operators, and instruments for formalin-fixed, paraffin-embedded tissue and 99.8% (615 of 616) for plasma. Analytical sensitivity was high with detection of 1% mutant sequence in formalin-fixed, paraffin-embedded tissue samples and as low as 25 mutant sequence copies/mL for plasma samples. The test also showed high overall concordance for formalin-fixed, paraffin-embedded tumor tissue as well as for plasma specimens when compared with MiSeq sequencing results. CONCLUSIONS.­: The KRAS Mutation Test v2 is a highly robust, reproducible, and sensitive test for the qualitative detection of 28 mutations in exons 2, 3, and 4 of the KRAS gene in both solid (tissue) and liquid (plasma) biopsies from colorectal cancer, non-small cell lung cancer, and pancreatic cancer, and is a convenient option for KRAS mutation testing.

Facial Erosive Pustular Dermatosis After Cosmetic Resurfacing.

Importance: Erosive pustular dermatosis (EPD) is a rare condition that typically affects actinically damaged skin of the scalp. Characterized by sterile pustules, erosions, and crusts, EPD is difficult to treat and heals slowly. The exact cause of EPD is unknown, although trauma is an inciting factor. Objective: To describe 3 women who presented with prolonged facial erosions after cosmetic resurfacing procedures, specifically fully ablative carbon dioxide laser or medium-depth chemical peel. Design, Setting, and Participants: This case series describes the clinical features, histopathological findings, laboratory results, and treatment of 3 patients with an ultimate diagnosis most consistent with facial EPD. Patients were evaluated between September 10, 2010, and May 6, 2016, in a dermatology clinic in an academic medical center. The patients were 3 women seeking diagnostic evaluation and therapeutic options for nonhealing facial erosions occurring after ablative procedures (carbon dioxide laser resurfacing or Jessner solution/trichloroacetic acid chemical peel). Main Outcomes and Measures: Histologic examination and wound culture from initial presentation as well as clinical follow-up documenting improvement with therapeutic interventions. Results: All 3 patients were women in their 50s or 60s for whom EPD was deemed to be the best diagnosis, after infection, immunobullous disorders, and other pustular dermatoses were considered. Histologic features were nonspecific. Treatment included a combination of topical and systemic therapies, such as corticosteroids, dapsone, isotretinoin, and/or antibiotics. Watchful waiting (tincture of time) appeared to be central to the healing process. Conclusions and Relevance: After cosmetic resurfacing, patients may develop EPD isolated to the face. As a diagnosis of exclusion that should be considered in patients who have nonhealing wounds following ablative procedures, EPD is challenging to treat and may require the use of anti-inflammatory agents. Recognizing this condition is important, especially as cosmetic procedures become more widespread.

Ablative Fractional Laser-Assisted Topical Fluorouracil for the Treatment of Superficial Basal Cell Carcinoma and Squamous Cell Carcinoma In Situ: A Follow-Up Study.

BACKGROUND: The authors previously reported the safety and short-term efficacy of ablative fractional laser (AFXL)-assisted delivery of topical fluorouracil in the treatment of superficial basal cell carcinoma (sBCC) and squamous cell carcinoma in situ (SCCis). OBJECTIVE: This follow-up study was conducted to assess whether tumor clearance was sustained in this cohort of patients at >9 months post-treatment. METHODS: Thirty primary sBCC or SCCis <2 cm on the trunk or extremities were treated with AFXL and a single application of topical 5-fluorouracil 5% under occlusion for 7 days. Among the 26 patients who achieved tumor clearance at 4 to 8 weeks post-treatment, 20 patients presented for this follow-up study and underwent shave biopsy to confirm histologic clearance. Mean follow-up time was 15 months. RESULTS: Considering those who had persistent tumor at 4 to 8 weeks post-treatment and those who presented for follow-up at >9 months post-treatment, overall treatment success was 79% (95% confidence interval: 67%-96%), with 92% (11/12) for SCCis and 67% (8/12) for sBCC. Neither the tumor location nor size significantly impacted treatment outcome (p = .96 and 0.87, respectively). CONCLUSION: Ablative fractional laser-assisted topical fluorouracil is a reasonable noninvasive treatment option for primary SCCis and sBCC, especially for lesions located in areas where self-application is not possible, or when clinician-administered therapy is preferred.

Treatment of Pearly Penile Papules with Fractionated CO2 Laser.

OBJECTIVE: Pearly penile papules are asymptomatic, benign growths distributed around the corona of the penis that can frequently be a source of significant psychological distress for the patient. Various treatment options are limited mainly by their complications. DESIGN: Two case reports and a review of the literature. SETTING: University academic setting. PARTICIPANTS: Two subjects of skin types I and V. MEASUREMENTS: Visual inspection and photographs were used to determine clearance. RESULTS: Two cases of pearly penile papules that were successfully treated using a fractionated CO2 laser. CONCLUSION: The fractionated CO2 laser is a well-tolerated treatment for pearly penile papules. Importantly, this modality is useful even in darker skin types.

A critical evaluation of clinical research study designs.

Interventional and observational studies have important roles in dermatology. The results from any study must be put in the context of the appropriate research design selection. RCTs are most useful in determining causality and effectiveness of treatment. Observational studies provide information about epidemiology and possible links between exposure and disease. Understanding the fundamentals underlying the various study designs is critical to both investigators and clinicians alike.

Laser hair removal: a review.

BACKGROUND: Unwanted hair growth is a common aesthetic problem. Laser hair removal has emerged as a leading treatment option for long-term depilation. OBJECTIVES: To extensively review the literature on laser hair removal pertaining to its theoretical basis, current laser and light-based devices, and their complications. Special treatment recommendations for darker skin types were considered. MATERIALS AND METHODS: A comprehensive literature search related to the long-pulse alexandrite (755 nm), long-pulse diode (810 nm), long-pulse neodymium-doped yttrium aluminum garnet (Nd:YAG; 1,064 nm), and intense pulsed light (IPL) system, as well as newer home-use devices, was conducted. RESULTS: The literature supports the use of the alexandrite, diode, Nd:YAG and IPL devices for long-term hair removal. Because of its longer wavelength, the Nd:YAG is the best laser system to use for pigmented skin. Further research is needed regarding the safety and efficacy of home-use devices. CONCLUSION: Current in-office laser hair removal devices effectively provide a durable solution for unwanted hair removal.

Intracellular degradation of elastin by cathepsin K in skin fibroblasts--a possible role in photoaging.

Solar elastosis is observed in the dermis of photoaged skin and is characterized by an accumulation of abnormal elastin in the extracellular space. Several proteases that degrade elastin in the extracellular space have been implicated in its formation. The lysosomal protease cathepsin K (catK) has recently been described to be highly expressed in skin fibroblasts under certain pathologic conditions. As cat K is one of the most potent mammalian elastases, we hypothesized that catK-mediated intracellular elastin degradation may play a role in the formation of solar elastosis. Immunostaining of cultured skin fibroblasts incubated with labeled elastin demonstrated internalization of extracellular elastin to lysosomes and its degradation by catK. Induction of catK expression in fibroblasts was observed both in vitro and in vivo after exposure to longwave UVA. In contrast to fibroblasts from young donors, cells from old donors failed to activate catK in response to UVA. These data suggest a role of intracellular elastin degradation by catK in the formation of solar elastosis. We propose that an age-related decline in catK activity, in particular after UV exposure, may promote the formation of actinic elastosis through a decline of orderly intracellular elastin degradation and subsequent accumulation of elastin in the extracellular space.

Significant impact of cutaneous T-cell lymphoma on patients' quality of life: results of a 2005 National Cutaneous Lymphoma Foundation Survey.

BACKGROUND: Cutaneous T-cell lymphoma (CTCL) can have a profound impact on a patient's health-related quality of life; however, little is known about its actual impact. The authors evaluated patients' perspectives on the impact of CTCL on physical functioning, lifestyle, emotional well being, and satisfaction with treatment. METHODS: A 4-page, self-administered questionnaire was mailed and made available online in March 2005 to the entire United States membership of the Mycosis Fungoides Foundation (n = 930 members). Outcome measures were patients' perspectives on the psychosocial impact of CTCL and the management of their disease. RESULTS: The response rate was 68%, and 93.6% of respondents were white. The majority of respondents had mycosis fungoides (89%). Respondents were bothered by skin redness (94%) and by the extent of symptoms that affected their choice of clothing (63%). For most patients, the disease had a functional impact, rendering them tired or affecting their sleep. Health distress was reported by almost all respondents, with 94% reporting that they worried about the seriousness of their disease and 80% worrying about dying from the disease. Sixty-two percent of respondents reported that their disease made them feel unattractive, 85% reported that their treatment made their disease seem more manageable, but 61% reported that they felt burdened financially by their disease. CONCLUSIONS: The high response rate and patients' responses to the survey provided compelling evidence that patients believed CTCL had a profound and severe impact on their functioning, emotional, and social well being. A striking health distress was prevalent in almost all respondents. Although the majority of patients reported that treatments made their disease more manageable, a significant proportion reported that they felt burdened financially by their disease.