A randomized, double-blind, placebo-controlled phase 3 skin cancer prevention study of {alpha}-difluoromethylornithine in subjects with previous history of skin cancer.

Preclinical studies have shown that the inhibition of ornithine decarboxylase (ODC) by alpha-difluoromethylornithine (DFMO) and resultant decreases in tissue concentrations of polyamines (putrescine and spermidine) prevents neoplastic developments in many tissue types. Clinical studies of oral DFMO at 500 mg/m(2)/day revealed it to be safe and tolerable and resulted in significant inhibition of phorbol ester-induced skin ODC activity. Two hundred and ninety-one participants (mean age, 61 years; 60% male) with a history of prior nonmelanoma skin cancer (NMSC; mean, 4.5 skin cancers) were randomized to oral DFMO (500 mg/m(2)/day) or placebo for 4 to 5 years. There was a trend toward a history of more prior skin cancers in subjects randomized to placebo, but all other characteristics including sunscreen and nonsteroidal anti-inflammatory drug use were evenly distributed. Evaluation of 1,200 person-years of follow-up revealed a new NMSC rate of 0.5 events/person/year. The primary end point, new NMSCs, was not significantly different between subjects taking DFMO and placebo (260 versus 363 cancers, P = 0.069, two-sample t test). Evaluation of basal cell (BCC) and squamous cell cancers separately revealed very little difference in squamous cell cancer between treatment groups but a significant difference in new BCC (DFMO, 163 cancers; placebo, 243 cancers; expressed as event rate of 0.28 BCC/person/year versus 0.40 BCC/person/year, P = 0.03). Compliance with DFMO was >90% and it seemed to be well tolerated with evidence of mild ototoxicity as measured by serial audiometric examination when compared with placebo subjects. The analysis of normal skin biopsies revealed a significant (P < 0.05) decrease in 12-0-tetradecanoylphorbol-13-acetate-induced ODC activity (month 24, 36, and 48) and putrescine concentration (month 24 and 36 only) in DFMO subjects. Subjects with a history of skin cancer taking daily DFMO had an insignificant reduction (P = 0.069) in new NMSC that was predominantly due to a marked reduction in new BCC. Based on these data, the potential of DFMO, alone or in combination, to prevent skin cancers should be explored further.

Dermatofibrosarcoma protuberans: a report on 29 patients treated by Mohs micrographic surgery with long-term follow-up and review of the literature.

BACKGROUND: Dermatofibrosarcoma protuberans (DFSP) is an uncommon tumor of the skin. Clinically, it often masquerades as a benign, indolent tumor on the trunk and extremities. Microscopically, it extends far beyond assessed clinical margins, spreading locally in the dermis, subcutaneous tissue, and muscle. The local recurrence rate in patients with DFSP who undergo wide local excision ranges from 0% to 21%. Recent preliminary reports indicate more consistently favorable cure rates with Mohs micrographic surgery (MMS). However, to date only a few scattered reports have documented long-term 5-year follow-up. The authors present data on 29 patients with DFSP who underwent MMS. In addition, they reviewed the medical literature to summarize the accumulated experience of MMS treatment in the management of DFSP. METHODS: The authors conducted a retrospective review of a series of 40 consecutive patients with DFSP who underwent MMS over the last 20 years. Of these, there were 29 patients with > 5 years of follow-up who formed the basis of the current review. The literature also was searched for patients with DFSP who underwent MMS with > 5 years of follow-up RESULTS: At the University of Wisconsin Mohs Surgery Clinic, 29 patients with > 5 years of follow-up were treated. There were 16 women and 13 men. Eight patients developed recurrent disease after previous non-Mohs treatment. Site distribution was 45% head and neck and 55% trunk and extremities. In the current series, there were no local recurrences, with a local 5-year cure rate of 100%. In the literature review, which included the current series, there were 136 patients with DFSP who underwent Mohs surgery with > 5 years of follow-up. Nine patients in the current series developed local recurrences, including five patients who underwent a second Mohs procedure. The local cure rates after the first and second Mohs surgeries were 93.4% and 98.5%, respectively. The rate (percent) and time to local recurrence was 50% at 3 years and 75% at 5 years. However, 25% of local recurrences appeared late, after the usual 5-year recommendation. CONCLUSIONS: In a series of 29 patients with of DFSP and in an accompanying update of the medical literature, 136 patients with DFSP underwent MMS with > 5 years of follow-up. There were no regional and/or distant metastases. However, late recurrences beyond the usual recommended 5-year follow-up may occur. Therefore, all patients with DFSP, especially those with recurrent tumors, should be followed for an extended period. The accumulated data continue to confirm that, when DFSP is discovered early and is accessible readily to excision by MMS, a favorable outcome can be expected with minimal trauma or sacrifice of adjacent normal structures and with a low recurrence rate.

Sebaceous carcinoma of the eyelids treated by mohs micrographic surgery: report of nine cases with review of the literature.

BACKGROUND: Ocular sebaceous carcinoma (SC) is a rare tumor of the eyelids. Clinically it frequently involves the upper lid in older women. Microscopically it tends to extend far beyond its assessed clinical margins. SC is characterized by a variety of tissue invasion mechanisms. It may spread by direct extension, be multifocal in advanced cases, and develop "skip areas" after trauma. Despite its ability to develop discontinuity, over the past two decades there have been several favorable case reports of SC treated by Mohs micrographic surgery (MMS). OBJECTIVE: To illustrate by case report the clinical presentation and management of patients with SC and to document our series of SC patients treated by MMS over the last 14 years. METHODS: A retrospective study was conducted of all cases of sebaceous carcinoma involving the ocular adnexa treated at the University of Wisconsin Mohs Surgery Clinic from 1987 to 2001. We also reviewed the accumulated medical literature of SC treated by MMS. RESULTS: In our series, there were nine cases of periocular SC. Five cases originated on the upper lid and four on the lower lid. Five of nine patients (55%) showed epithelial invasion. One patient developed a local recurrence 1.5 years later and was treated by orbital exenteration. This patient has had no evidence of disease for 5 years. Eight of nine patients (88%) had no evidence of local recurrence with a follow-up of 1-14 years. In our literature review we found 40 additional cases of orbital SC treated by MMS. Intraepithelial spread of SC was found in 50% of patients (24 of 48). Six patients developed local recurrence. The overall local cure rate following MMS is 87.8% (43 of 49), with a mean follow-up of 3.1 years. The regional metastatic rate was 8% (4 of 49). There were no deaths reported. CONCLUSION: We present nine new cases of SC. The age, sex, and site distribution are compatible with other SC cases reported in the literature. We reviewed the medical literature and compiled 49 cases of SC treated by Mohs surgery. Intraepithelial spread was discovered in 50% of the cases. Multifocal disease or discontinuity was present in 6% (3 of 49). Mohs surgery appears to be an effective method for excising the microscopic ramifications of primary SC. When feasible, we recommend in SC cases where intraepithelial pagetoid spread has been observed, that removal of another Mohs layer should be considered in order to provide an additional assurance layer against local tumor recurrence.