Non-Invasive Gene Expression Testing to Rule Out Melanoma.

The Pigmented Lesion Assay (PLA) is a gene expression test that helps rule out melanoma and has the potential to reduce the need for surgical biopsies of atypical pigmented skin lesions. Utilizing a new technological platform for the non-invasive profiling of skin, the assay analyzes samples collected from adhesive patches for expression of two key genes (PRAME and LINC00518) known to be overexpressed in melanoma. The test result is binary (positive/negative) based on the detection of one or both genes. PLA positive cases are generally biopsied to establish the histopathologic diagosis, while PLA negative cases are considered for ongoing monitoring. The combination of visual inspection with histopathology, the current gold standard for melanoma diagnosis, has a relatively low negative predictive value (NPV) of approximately 83%, meaning that 17% of melanomas will be interpreted as benign lesions. In contrast, the PLA has a very high NPV (>99%). Further, with its high specificity (69-91%), use of the PLA can reduce the number of false positive samples subjected to histopathology review. By adding the PLA to the current care pathway, the number of surgical biopsies needed to find a melanoma (number needed to biopsy) is markedly reduced from 20-25 biopsies for dermatologists and 39 biopsies for physician assistants, to an average of 2.7. To date, unnecessary surgical procedures of benign lesions have been reduced by 88% based on a sample of more than 20,000 analyzed cases. This has resulted in fewer missed melanomas and significant cost savings to health care systems.

Actikerall™ (5-Fluorouracil 0.5% and Salicylic Acid 10%) Topical Solution for Patient-directed Treatment of Actinic Keratoses.

Actinic keratosis (AK), a common cutaneous lesion with the potential to transform into squamous cell carcinoma, has traditionally been treated with ablative and/or surgical procedures. Recently, a topical formulation combining 0.5% 5-fluorouracil with 10% salicylic acid (5-FU-SA) was introduced in Europe under the trade name Actikerall™ for the treatment of grade I/II AKs. In a single randomized phase III trial, 5-FU-SA was shown to be superior to diclofenac 3% gel in hyaluronic acid, as measured by the histological clearance of one defined lesion (72% vs. 59.1%) and by complete clinical clearance (55.4% vs. 32.0%). 5-FU-SA should be applied once daily to a total area of up to 25 cm(2), which may include the lesion(s) and a small area of surrounding skin (rim of healthy skin should not exceed 0.5 cm), for up to 12 weeks. The most common side effects are local inflammation and pruritus at the application site, and no serious adverse effects have been reported to date. Now commercially available in Canada, 5-FU-SA represents a patientapplied therapeutic option for the treatment of both overt and subclinical AKs.

The role of cosmeceuticals in antiaging therapy.

As baby boomers get older, they have shown an increasing interest in maintaining a youthful appearance. As a result, there has been a corresponding increase in topical antiaging formulations, which are commonly referred to as cosmeceuticals. These products come with a seemingly limitless number of key active ingredients and claims of reducing the signs of aging and/or maintaining a youthful appearance. This paper reviews the more common cosmeceutical ingredients.

Imiquimod 5% cream for the treatment of actinic keratoses.

Actinic keratoses (AKs) are premalignant inflammatory skin lesions with the potential to transform into squamous cell carcinoma (SCC). There are several treatment options available for patients presenting with multiple AKs. Imiquimod is believed to stimulate and enhance host immune responses locally against skin tumors and viral infections. Five clinical studies to date have demonstrated its safety and efficacy in the treatment of actinic keratoses. Long-term follow-up studies examining recurrence rates are limited.

Topical 3% diclofenac in 2.5% hyaluronan gel for the treatment of actinic keratoses.

Actinic Keratoses (AKs) are epidermal skin lesions that have the potential to develop into squamous cell carcinoma. Many of the treatment options available can cause discomfort, pain or skin irritation. Topical 3% diclofenac in 2.5% hyaluronan gel (Solaraze, Bioglan Pharma) is a relatively new treatment that has been shown to be effective and well tolerated for the treatment of AKs.

Topical treatment of actinic keratoses with 3.0% diclofenac in 2.5% hyaluronan gel.

BACKGROUND: Actinic keratoses (AKs) are premalignant skin lesions, which, if left untreated, can develop into squamous cell carcinoma. Current treatments for AKs are destructive and are often associated with significant adverse events. The development of an effective and well-tolerated topical treatment for AK is desirable. OBJECTIVES: To evaluate the efficacy and safety of 3.0% diclofenac in 2.5% hyaluronan gel as a treatment for AK. METHODS: This was a multicentre, double-blind, placebo-controlled study in which 195 patients with at least five AKs in up to three designated treatment blocks were randomized to four treatment groups. Patients randomized into the active treatment groups A30 (n = 49) and A60 (n = 48) received topical treatment with 3.0% diclofenac in 2.5% hyaluronan gel 0.5 g twice daily for 30 or 60 days, respectively. Patients in the placebo (vehicle gel) groups V30 (n = 49) and V60 (n = 49) received topical treatment with 2.5% hyaluronan gel 0.5 g twice daily for 30 or 60 days, respectively. Treatment efficacy was assessed by target and cumulative lesion number scores (TLNS and CLNS, respectively) and lesion total thickness score (TTS). Investigator and patient global improvement indices (IGII and PGII) were also used to rate overall improvement. RESULTS: Compared with placebo, significantly more patients given active treatment for 60 days had TLNS = 0 (33% vs. 10%, P < 0.05; an improvement of 64% compared with 34% with placebo), CLNS = 0 (31% vs. 8%, P < 0.05; an improvement of 54% compared with 23% with placebo) and TTS = 0 (25% vs. 6%, P < 0.05; an improvement of 59% compared with 31% with placebo). The IGII and PGII scores were also significantly better when active treatment was compared with placebo (P < 0.05). Both treatments were generally well tolerated and the incidence of the most common adverse events was similar between groups. CONCLUSIONS: Treatment with 3.0% diclofenac in 2.5% hyaluronan gel was effective when used for 60 days and was well tolerated in patients with AK.

Predictors of sunburn among Canadian adults.

BACKGROUND: Data from the 1996 National Survey on Sun Exposure & Protective Behaviors (4,023 respondents) were analyzed to identify independent predictors of sunburn among adult Canadians. METHODS: Multivariate models predicting sunburn odds were developed using unconditional logistic regression. Backward elimination model selection was used to identify independent predictors of sunburn. RESULTS: Nonbehavioral characteristics found to predict sunburn were younger age, male sex, light skin color, nonblack hair color, and birthplace in North America or Europe. Behavioral predictors of sunburn included high awareness of the UV Index, working outdoors in the summer, longer leisure time in the sun, forgetfulness about protecting oneself from the sun, and seeking a tan. Sun avoidance between 11 AM and 4 PM was associated with lower odds of sunburn, while seeking shade when outside and use of protective clothing showed nonsignificant associations with lower sunburn odds. Sunscreen use was found to have a nonsignificant positive association with sunburn. CONCLUSIONS: These findings highlight risk factors to be considered in the targeting of sunburn reduction strategies to high-risk groups and suggest that sun avoidance, seeking shade, and use of protective clothing may be effective in preventing sunburn.

Dural melanoma associated with ocular melanosis and multiple blue nevi.

BACKGROUND: Primary meningeal melanomas of the central nervous system (CNS) are a rare malignant process with the majority originating from the leptomeninges. Primary dural melanomas have been reported to occur in isolation or in conjunction with Nevus of Ota. The association of primary dural melanoma with multiple cutaneous blue nevi has not been reported previously. OBJECTIVE: To describe a case of a 41-year-old Asian woman patient with a primary dural melanoma that arose in association with ocular melanosis and multiple cutaneous blue nevi. The patient is alive almost more than 8 years after subtotal and subsequent total resection of her primary tumor. Primary dural melanomas, Nevus of Ota, and blue nevi are discussed in relation to their coexistence and potential for intracranial melanoma. CONCLUSION: CNS melanoma is regarded as an extremely aggressive disease with poor prognosis. This case and previous reports of dural melanomas occurring in isolation or with Nevus of Ota have demonstrated relatively prolonged survival after surgical intervention. We conclude that dural melanomas are less aggressive tumors requiring surgical extirpation only.

Varicella zoster virus. Recent advances in management.

OBJECTIVE: To provide an update on strategies for managing varicella zoster virus (VZV) and for preventing and treating established postherpetic neuralgia (PHN). QUALITY OF EVIDENCE: Treatment guidelines are based on randomized clinical trials. Recommendations concerning other aspects of VZV management (e.g., vaccination) are based mainly on expert opinion. MAIN MESSAGE: Varicella and herpes zoster caused by VZV can give rise to serious morbidity and mortality and should be treated. For preventing chickenpox, safe and effective immunization is widely recommended. Treating varicella-exposed seronegative pregnant women requires special attention because the virus can harm expectant mothers, fetuses, and newborns. The antiviral drugs, acyclovir, valacyclovir, and famciclovir, have been approved for treating herpes zoster and have a role in reducing the duration of PHN. Established PHN can be managed with analgesics, tricyclic antidepressants, and other agents. CONCLUSION: Vaccination and antiviral and other systemic agents can substantially reduce the morbidity associated with VZV infection.

Broad-spectrum sunscreen use and the development of new nevi in white children: A randomized controlled trial.

CONTEXT: High nevus density is a risk factor for cutaneous malignant melanoma. Melanocytic nevi originate in childhood and are largely caused by solar exposure. OBJECTIVE: To determine whether use of broad-spectrum, high-sun protection factor (SPF) sunscreen attenuates development of nevi in white children. DESIGN: Randomized trial conducted June 1993 to May 1996. SETTING AND PARTICIPANTS: A total of 458 Vancouver, British Columbia, schoolchildren in grades 1 and 4 were randomized in 1993. After exclusion of nonwhite children and those lost to follow-up or with missing data, 309 children remained for analysis. Each child's nevi were enumerated at the start and end of the study in 1996. INTERVENTION: Parents of children randomly assigned to the treatment group (n=222) received a supply of SPF 30 broad-spectrum sunscreen with directions to apply it to exposed sites when the child was expected to be in the sun for 30 minutes or more. Children randomly assigned to the control group (n=236) received no sunscreen and were given no advice about sunscreen use. MAIN OUTCOME MEASURE: Number of new nevi acquired during the 3 years of the study, compared between treatment and control groups. RESULTS: Children in the sunscreen group developed fewer nevi than did children in the control group (median counts, 24 vs 28; P=.048). A significant interaction was detected between freckling and study group, indicating that sunscreen use was much more important for children with freckles than for children without. Modeling of the data suggests that freckled children assigned to a broad-spectrum sunscreen intervention would develop 30% to 40% fewer new nevi than freckled children assigned to the control group. CONCLUSIONS: Our data indicate that broad-spectrum sunscreens may attenuate the number of nevi in white children, especially if they have freckles. JAMA. 2000.

Clinical significance of skin biopsies in the diagnosis and management of graft-vs-host disease in early postallogeneic bone marrow transplantation.

OBJECTIVE: To determine the value of skin biopsies in the management of suspected graft-vs-host disease (GVHD) within 30 days of allogeneic bone marrow transplantation (BMT). DESIGN: Retrospective study based on review of a BMT database. SETTING: Leukemia/BMT ward of a tertiary care, university teaching hospital. PATIENTS: One hundred and eighty-seven consecutive patients who received allogeneic BMT between January 1, 1994, and June 30, 1997, at Vancouver General Hospital, Vancouver, British Columbia. MAIN OUTCOME MEASURES: (1) Skin biopsy frequency for patients with rashes suggestive of acute GVHD; (2) clinical significance of skin biopsy in the management of patients with suspected acute GVHD after BMT; (3) relationship between severity of clinical GVHD and the likelihood to receive GVHD therapy; and (4) relationship between biopsy status or biopsy result and outcome of BMT (acute and chronic GVHD, transplant-related mortality, and overall and event-free survival). RESULTS: During the early post-BMT period (<30 days after BMT), 88 patients had rashes suggestive of acute GVHD; of these, 51 (58%) underwent skin biopsy to confirm the diagnosis. Skin biopsies were performed more often for higher clinical stages of cutaneous GVHD. There was no significant difference between the patients with positive biopsy findings and those with negative findings, either in the clinical severity of acute GVHD or in likelihood to receive treatment for GVHD. Most (85%) of the patients who underwent biopsies and received GVHD therapy had treatment initiated before skin biopsies were performed or before the results were available. The higher the clinical grade of overall acute GVHD, the more likely it was that the patients were treated for GVHD (P<.001). The outcome of BMT was not influenced by the skin biopsy status or biopsy result. CONCLUSIONS: The biopsy findings correlated poorly with the clinical severity of skin rash suggestive of acute GVHD soon after BMT. The decision to treat suspected acute GVHD depended not on skin biopsy findings but rather on clinical severity of acute GVHD. In this regard, skin biopsy has a limited role in the management of patients early after allogeneic BMT.

Follow-up and evaluation of skin cancer screening in British Columbia.

BACKGROUND: Skin cancer screening is thought to be a useful public health tool for the early detection of skin cancers. However, few studies have reported on follow-up and outcome of subjects who have a positive screen. OBJECTIVE: The aims of this study were to evaluate attendance at skin cancer screening clinics in British Columbia for the period 1994 and 1995 and to assess follow-up outcome among participants who were identified to have a potentially serious skin lesion that warranted further medical review. METHODS: A self-administered questionnaire was sent to participants screening positive for skin cancer and to their attending physicians. RESULTS: Five hundred twenty people were screened. Of these, 105 were referred for evaluation of a potential malignancy or precursor lesion. One melanoma, 3 basal cell carcinomas, 4 atypical nevi, and 1 actinic keratosis were histologically confirmed in 76 referred participants for whom follow-up information was available. The positive predictive values ranged from 17% to 89% depending on the screening diagnosis. Several false-positive results and one false-negative result were observed. Reasons for not seeking recommended follow-up were addressed. CONCLUSIONS: Our yield and positive predictive values for different screening diagnoses were virtually identical to those previously reported in larger US studies. Improved communication between screening physicians and screening participants may improve follow-up rates in those people who would benefit from further medical care.

Is there a rationale for the drugs used in hair transplantation surgery?

BACKGROUND: Various medications may be used before, during, or after hair transplantation surgery (HTS) with the aims of maximizing patient comfort, reducing unwanted side effects, and improving the results of HTS. OBJECTIVE: The objectives of this study were to determine the current practice pattern and rationale for drug prescribing by a group of leading hair transplant surgeons and to review the literature for the evidence upon which these prescribing patterns were based. METHODS: A postal questionnaire was sent to 16 hair transplant surgeons from the United States and Canada, and the answers were analyzed. The relevant evidence-based literature concerning HTS was reviewed by medicine search. RESULTS: Questionnaires suitable for analysis were received from 14 of the surgeons. There were many differences in the pattern of prescribing drugs for the HTS procedure. There was general agreement about the use of local anesthetics but no consensus about the withholding of agents that might increase bleeding; the use of pre- and postoperative analgesics; the use of topical and systemic antibiotics; the use of corticosteroids; or minoxidil. Randomized controlled studies relating to these issues for HTS were not identified in the literature. CONCLUSION: A lack of consensus exists about the drugs used in HTS based on a lack of evidence-based medicine.

Canadian National Survey on Sun Exposure & Protective Behaviours: methods.

This article describes the methods used for the 1996 Canadian National Survey on Sun Exposure & Protective Behaviours. A 55-item random-digit-dialling telephone household survey of people 15 years of age or more was completed in 1996. Items assessed were daily sun exposure and protective behaviours, as well as other sun-related behaviours and attitudes. Data were collected regarding sun-related behaviours during leisure, work time and winter holidays, as well as for children 12 years of age or less (as reported by parents). To test for an effect on the survey response rate, a letter of introduction was sent to 40% of the households. The survey response rate was 69% (4023 successfully completed surveys out of 5847 households included in the sample). The response rate achieved in the subset that received the introductory letter was 75%. This survey is the first to establish national population estimates for sun exposure and protective behaviours in Canada.