Neil A. Swanson

Ingenol mebutate gel for actinic keratosis

BACKGROUND Actinic keratosis is a common precursor to sun-related squamous-cell carcinoma. Treating actinic keratoses and the surrounding skin area (i.e., field therapy) can eradicate clinical and subclinical actinic keratoses. Topical field therapy currently requires weeks or months of treatment. We investigated the efficacy and safety of a new topical field therapy for actinic keratosis, ingenol mebutate gel (0.015% for face and scalp and 0.05% for trunk and extremities). METHODS In four multicenter, randomized, double-blind studies, we randomly assigned patients with actinic keratoses on the face or scalp or on the trunk or extremities to receive ingenol mebutate or placebo (vehicle), self-applied to a 25-cm(2) contiguous field once daily for 3 consecutive days for lesions on the face or scalp or for 2 consecutive days for the trunk or extremities. Complete clearance (primary outcome) was assessed at 57 days, and local reactions were quantitatively measured. RESULTS In a pooled analysis of the two trials involving the face and scalp, the rate of complete clearance was higher with ingenol mebutate than with placebo (42.2% vs. 3.7%, P<0.001). Local reactions peaked at day 4, with a mean maximum composite score of 9.1 on the local-skin-response scale (which ranges from 0 to 4 for six types of reaction, yielding a composite score of 0 to 24, with higher numbers indicating more severe reactions), rapidly decreased by day 8, and continued to decrease, approaching baseline scores by day 29. In a pooled analysis of the two trials involving the trunk and extremities, the rate of complete clearance was also higher with ingenol mebutate than with placebo (34.1% vs. 4.7%, P<0.001). Local skin reactions peaked between days 3 and 8 and declined rapidly, approaching baseline by day 29, with a mean maximum score of 6.8. Adverse events were generally mild to moderate in intensity and resolved without sequelae. CONCLUSIONS Ingenol mebutate gel applied topically for 2 to 3 days is effective for field treatment of actinic keratoses. (Funded by LEO Pharma; ClinicalTrials.gov numbers, NCT00742391, NCT00916006, NCT00915551, and NCT00942604.).

Mohs micrographic surgery for the treatment of dermatofibrosarcoma protuberans. Results of a multiinstitutional series with an analysis of the extent of microscopic spread.

BACKGROUND Dermatofibrosarcoma protuberans (DFSP) is an uncommon soft-tissue tumor of the skin; its microscopic extent of invasion beyond the grossly visible tumor is frequently difficult to appreciate. Although wide local excision has been the standard treatment of DFSP, recurrence rates range from 11% to 53%. Because Mohs micrographic surgery allows the extent of excision to be tailored to the microscopic extent of tumor, we evaluated this technique for the treatment of primary and recurrent DFSP. OBJECTIVE Our purpose was to determine the local recurrence rate and microscopic extent of spread of primary and recurrent DFSP after treatment with Mohs micrographic surgery. METHODS The records of 58 patients with primary and recurrent DFSP treated with Mohs micrographic surgery at three institutions were reviewed and the macroscopic and microscopic extents of tumor were recorded. RESULTS One patient with a twice-recurrent DFSP had another recurrence after Mohs micrographic surgery, for an overall local recurrence rate of 2% (zero for primary tumors and 4.8% for recurrent tumors). There were no cases of regional or distant metastases. Macroscopic tumor size ranged from 0.3 x 0.6 cm to 30 x 20 cm, whereas microscopic (postoperative) size ranged from 1.8 x 1.0 cm to 35 x 40 cm. We calculated the likelihood that a given width of excision around the macroscopic tumor would clear the entire microscopic extent of tumor. Standard wide excision with a width of 1 cm around the primary tumor would have left microscopic residual tumor in 70.7%; a width of 2 cm, 39.7%; 3 cm, 15.5%; and 5 cm, 5.2%. Even an excision width of 10 cm would not have cleared the microscopic extent of some tumors, despite taking a huge excess of normal tissue. CONCLUSION Treatment of primary and recurrent DFSP by Mohs micrographic surgery results in a low recurrence rate because of the ability of the technique to permit the detection and excision of microscopic tumor elements in even the most asymmetric tumors. Whatever type of surgery is chosen to treat DFSP, it is necessary to assess the entire perimeter of the tumor for microscopic extension and to achieve tumor-free margins in all directions.

Mohs Surgery: Technique, Indications, Applications, and the Future

Each year, it is estimated, more than 500,000 new cases of nonmelanoma skin cancer develop. The majority of these cutaneous neoplasms are treated by various modalities that include excision, electrodesiccation and curettage, cryosurgery, and irradiation, with greater than 90% success. Certain of the remaining primary tumors, as well as recurrent carcinomas, present a demanding therapeutic challenge. For these lesions, Mohs surgery has evolved as the most reliable and cost-effective treatment modality, offering maximal preservation of normal tissue and therefore the lowest functional and cosmetic morbidity. In this review, the history and evolution of Mohs surgery and the technique itself will be briefly outlined. The indications for Mohs surgery, together with methods of handling the postoperative wound and future applications of the technique, will be discussed in detail.

Abscess formation and local necrosis after treatment with Zyderm or Zyplast Collagen Implant

The incidence, clinical presentation, pathophysiology, and possible treatment of two rare but clinically meaningful complications of tissue augmentation with Zyderm and Zyplast Collagen Implant are described. Abscesses as a manifestation of hypersensitivity to bovine collagen occur rarely (4 in 10,000 cases) and may persist for days to weeks. Periods of remission and exacerbation may occur from 1 month to more than 24 months. Localized tissue necrosis also occurs rarely (9 in 10,000 cases) after implantation and is probably the result of local vascular interruption and not hypersensitivity. The incidence varies greatly between the anatomic sites of implantation; more than half the reported cases involve the glabella. Evidence strongly suggests that the increased vulnerability of the glabellar region is due to its unique vascular distribution.

Imiquimod 2.5% and 3.75% for the treatment of actinic keratoses: Results of two placebo-controlled studies of daily application to the face and balding scalp for two 2-week cycles

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 (> or =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.

Mohs' micrographic surgery using frozen sections alone may be unsuitable for detecting single atypical melanocytes at the margins of melanoma in situ

Summary Background It remains questionable whether micrographic surgery with frozen sections is an appropriate technique for excision of melanoma in situ (MIS) of the lentigo maligna type. Advocates of the technique have interpreted MIS as being histologically defined by nests and contiguous atypical melanocytes on the basal layer. Others, however, have viewed the periphery of MIS as consisting of scattered single atypical melanocytes, a finding that may be difficult or impossible to establish on frozen sections.

Dermal implants: Safety of products injected for soft tissue augmentation

Soft tissue augmentation is a frequently performed outpatient operation. Products available for soft tissue augmentation vary in chemistry, clinical indications, and toxicity. This review examines safety and efficacy data for collagen implants (Zyderm and Zyplast), gelatin matrix implants (Fibrel), and injectable silicone. Soft tissue augmentation requires excellent technique to achieve excellent clinical efficacy. When used appropriately, the available products for soft tissue augmentation have few complications or adverse reactions.

Clinical and histologic trends of melanoma

BACKGROUND Several changing clinical and histopathologic melanoma trends occurred from the 1950s to the 1980s. OBJECTIVE The purpose of this study was to evaluate melanoma trends during the past decade and to compare present trends to those documented during the past four decades. METHODS Sex, age at diagnosis, location, tumor thickness, stage, and histologic subtypes were evaluated from 1984 to 1995 and compared with trends during the past four decades. RESULTS Most changing trends from the past four decades have slowed or stabilized during the past decade. CONCLUSION Complete reporting of all melanomas to central tumor registries is necessary to accurately analyze present and future melanoma trends. Ongoing and new prevention and control strategies beginning at birth may be necessary to continue the positive efforts to curtail the melanoma epidemic.

Identification of common polymorphisms in the coding sequence of the human MSH receptor (MCIR) with possible biological effects

The extension locus has been identified in many mammalian species as a gene that determines the relative amounts of eumelanin and phaeomelanin pigments in hair and skin. In at least three species, this locus has been demonstrated to encode the melanocyte‐stimulating hormone receptor (MC1‐R), and functionally variant alleles have been demonstrated to cause a broad range of pigmentation phenotypes. To test for MC1‐R allelic variation in man, genomic DNA was extracted from skin samples collected from patients with different skin types (I–VI), and eye and hair color. A PCR‐based approach was used to amplify the full‐length coding sequence of the MC1‐R and the resulting products were sequenced. Two polymorphic alleles were identified with single point mutations in the coding sequence: a valine‐to‐methionine substitution at position 92 (V92M), and an aspartic acid‐to‐glutamic acid substitution at position 84 (D84E). RFLP analysis demonstrated the presence of the V92M allele in 4 out of 60 (6.6%) of individuals examined, predominantly those with blue eyes and blond hair. This polymorphism was found in both heterozygous and homozygous states in individuals with type I skin. The D84E allele was found in one individual with skin type I; this person also has the V92 M allele and thus is a compound heterozygote.

Topical minoxidil for hair regrowth

Minoxidil, a potent peripheral vasodilator used orally for refractory hypertension, has produced hypertrichosis. To determine the efficacy and safety of 1% or 5% topical minoxidil for the stimulation of scalp hair regrowth, we studied fifteen normotensive patients, five with androgenic alopecia and ten with alopecia areata diagnosed clinically and by biopsy, for 12 months. Three of five patients with androgenic alopecia using 5% minoxidil for 12 months noted hair regrowth, ranging from minimally observable hair to an appreciable restoration of larger, pigmented, terminal hair in one patient. Among the patients with androgenic alopecia, regrowth response corresponded to the serum minoxidil blood levels. None of the patients with alopecia areata receiving either 1% or 5% minoxidil noted hair regrowth despite comparable minoxidil blood levels. Improved local absorption of topical minoxidil solution may promote hair regrowth in androgenic alopecia.