Kenneth G. Linden

Chemoprevention of Nonmelanoma Skin Cancer With Celecoxib: A Randomized, Double-Blind, Placebo-Controlled Trial

Background Preclinical studies indicate that the enzyme cyclooxygenase 2 plays an important role in ultraviolet-induced skin cancers. We evaluated the efficacy and safety of celecoxib, a cyclooxygenase 2 inhibitor, as a chemopreventive agent for actinic keratoses, the premalignant precursor of nonmelanoma skin cancers, and for nonmelanoma skin cancers, including cutaneous squamous cell carcinomas (SCCs) and basal cell carcinomas (BCCs). Methods A double-blind placebo-controlled randomized trial involving 240 subjects aged 37–87 years with 10–40 actinic keratoses was conducted at eight US academic medical centers. Patients were randomly assigned to receive 200 mg of celecoxib or placebo administered orally twice daily for 9 months. Subjects were evaluated at 3, 6, 9 (ie, completion of treatment), and 11 months after randomization. The primary endpoint was the number of new actinic keratoses at the 9-month visit as a percentage of the number at the time of randomization. In an intent-to-treat analysis, the incidence of actinic keratoses was compared between the two groups using t tests. In exploratory analyses, we evaluated the number of nonmelanoma skin cancers combined and SCCs and BCCs separately per patient at 11 months after randomization using Poisson regression, after adjustment for patient characteristics and time on study. The numbers of adverse events in the two treatment arms were compared using χ2 or Fisher exact tests. All statistical tests were two-sided. Results There was no difference in the incidence of actinic keratoses between the two groups at 9 months after randomization. However, at 11 months after randomization, there were fewer nonmelanoma skin cancers in the celecoxib arm than in the placebo arm (mean cumulative tumor number per patient 0.14 vs 0.35; rate ratio [RR] = .43, 95% confidence interval [CI] = 0.24 to 0.75; P = .003). After adjusting for age, sex, Fitzpatrick skin type, history of actinic keratosis at randomization, nonmelanoma skin cancer history, and patient time on study, the number of nonmelanoma skin cancers was lower in the celecoxib arm than in the placebo arm (RR = 0.41, 95% CI = 0.23 to 0.72, P = .002) as were the numbers of BCCs (RR = 0.40, 95% CI = 0.18 to 0.93, P = .032) and SCCs (RR = 0.42, 95% CI = 0.19 to 0.93, P = .032). Serious and cardiovascular adverse events were similar in the two groups. Conclusions Celecoxib may be effective for prevention of SCCs and BCCs in individuals who have extensive actinic damage and are at high risk for development of nonmelanoma skin cancers.

Psoriasis: current perspectives with an emphasis on treatment

An individualized treatment regimen is necessary for each patient with psoriasis because of the diverse nature of the disease. The manifestation of psoriasis, the severity and extent of the lesions, and the medical history and lifestyle of the patient are important factors that determine the selection of treatment, but in general therapies with the fewest side effects are preferred. First-line topical treatments are corticosteroids, calcipotriene, and tazarotene. If topical treatments are unsuccessful, phototherapy with ultraviolet B or photochemotherapy with psoralens plus ultraviolet A (PUVA) are the next choices. If psoriasis fails to respond to an adequate trial of topical therapy or phototherapy, systemic therapies including methotrexate, acitretin, or cyclosporin should be initiated. Because the regimens involved in systemic and phototherapy are complex and require frequent dose adjustments and specialized equipment, the patient should be referred to a dermatologist when topical therapy is not effective.

Netherton syndrome: a case report and review of the literature.

Netherton syndrome is a rare disorder inherited in an autosomal recessive pattern consisting of ichthyosiform dermatosis, hair shaft abnormalities (trichorrhexis invaginata), and an atopic diathesis. Patients with Netherton syndrome have been found to have a mutation on chromosome 5q32 in a gene named SPINK5 (serine protease inhibitor, Kazal type‐5), which encodes an inhibitor of serine proteases called LEKTI.

Chemoprevention of Nonmelanoma Skin Cancer: Experience with a Polyphenol from Green Tea

Nonmelanoma skin cancer is extremely common and is increasing in incidence. It would be very useful to have forms of therapy that would prevent precancerous changes from going on to form cancer, or to reverse the precancerous changes. Epidemiologic evidence in humans, in vitro studies on human cells, and clinical experiments in animals have identified polyphenol compounds found in tea to be possibly useful in reducing the incidence of various cancers, including skin cancer. To examine the potential for a polyphenol from green tea, epigallocatechin gallate, to act as a chemopreventive agent for nonmelanoma skin cancer, a randomized, double-blind, placebo-controlled phase II clinical trial of topical epigallocatechin gallate in the prevention of nonmelanoma skin cancer was performed.

A Randomized, Double-Blind, Placebo-Controlled Phase II Clinical Trial of Lovastatin for Various Endpoints of Melanoma Pathobiology

On the basis of large cardiovascular clinical trials of lipid-lowering agents that showed a considerable decrease in the incidence of primary melanomas in the active agent arm, we have carried out a randomized, double-blind clinical trial examining the impact of lovastatin on various biomarkers of melanoma pathogenesis. Subjects with at least two clinically atypical nevi were randomized to receive oral lovastatin or placebo for a 6-month period. Clinical, histopathologic, and molecular biomarkers were evaluated for change in the two groups. Eighty subjects were randomized, evaluable, and included in the analyses. Lovastatin showed no benefit in comparison with placebo in the primary endpoint of decreasing the level of histopathologic atypia, nor in any of the secondary endpoints of decreasing clinical atypia, impact on nevus number, nor in showing significant changes in any of the molecular biomarkers. There were no significant differences in adverse event profiles for lovastatin compared with placebo. The lovastatin arm did show a significant and considerable decrease in total serum cholesterol and serum low-density lipoprotein (LDL) levels compared with placebo, an expected result. This finding bolsters confidence in subject compliance. Given the results of this trial, it is concluded that if lovastatin were to lower the incidence of melanoma, it would appear not to be doing so by reversing atypia of precursor atypical nevi over the 6-month time frame studied. Further research into the pathogenesis of melanoma and in other potential chemopreventive agents is needed. Cancer Prev Res; 7(5); 496–504. ©2014 AACR.

Medical students educate teens about skin cancer: what have we learned?

Skin cancer is a serious societal problem, and public awareness outreach, including to youth, is crucial. Medical students have joined forces to educate adolescents about skin cancer with significant impacts; even one 50-min interactive outreach session led to sustained changes in knowledge and behavior in a cohort of 1,200 adolescents surveyed. Medical students can act as a tremendous asset to health awareness public outreach efforts: enthusiastic volunteerism keeps education cost-effective, results in exponential spread of information, reinforces knowledge and communication skills of future physicians, and can result in tangible, life-saving benefits such as early detection of melanoma.

Localized pretibial bullous pemphigoid arising in a patient on pembrolizumab for metastatic melanoma

Author(s): Amber, Kyle T; Valdebran, Manuel; Lu, Yuxin; De Feraudy, Sebastien; Linden, Kenneth G

Awareness of Surgical Smoke Risks and Assessment of Safety Practices During Electrosurgery Among US Dermatology Residents

This study assessed clinician awareness of surgical smoke risks and current safety practices during active electrosurgery among dermatology residents.

Letter: clear margins after the use of imatinib mesylate prior to resection of extensive dermatofibrosarcoma protuberans.

Wright and Petersen reported a case of a patient with dermatofibrosarcoma protuberans (DFSP) treated with imatinib mesylate for 5 months prior to Mohs micrographic surgery (MMS) after two previous resections with subsequent recurrence. All margins were clear on permanent frozen sections of the surgical specimens. Clinically, the patient has not had any evidence of disease for 16 months. The authors suggest the need for large-scale clinical trials before presurgical treatment with imatinib mesylate, which could be defined as the new standard of care.

Diffuse cutaneous mastocytosis: Case report and literature review

A 6‐month‐old boy was referred to our burn unit with a recurrent bullous dermatitis, fever, and emesis, originally diagnosed as staphylococcal scalded skin syndrome (SSSS) at an outside hospital. Infectious workup was negative and shave biopsy revealed a dense, diffuse dermal infiltrate of mast cells, consistent with diffuse cutaneous bullous mastocytosis—a rare variant of cutaneous mastocytosis. Treatment included a prolonged course of corticosteroids and antihistamines. Recognition of this rare form of mastocytosis is important, as it can be easily mistaken for other pediatric bullous diseases and is associated with life‐threatening complications including vasodilation, anaphylactic shock, gastrointestinal bleeding, and death.