Reduction of immunosuppression for transplant-associated skin cancer: expert consensus survey.

BACKGROUND: Reduction of immunosuppression is considered a reasonable adjuvant therapeutic strategy in solid-organ transplant recipients experiencing multiple or high-risk skin cancers. However, the literature provides no guidance about what threshold of cancer development would warrant initiation of reduction of immunosuppression. OBJECTIVES: To develop expert consensus guidelines for initiation of reduction of transplant-associated immunosuppression for solid-organ transplant recipients with severe skin cancer. METHODS: An expert consensus panel was convened by the International Transplant Skin Cancer Collaborative and Skin Care for Organ Transplant Patients Europe Reduction of Immunosuppression Task Force. Thirteen hypothetical patient scenarios with graduated morbidity and mortality risks were presented and mean and mode expert opinions about appropriate level of reduction of systemic immunosuppression (mild, moderate, severe) were generated. RESULTS: Mild reduction of transplant-associated immunosuppression was considered warranted once multiple skin cancers per year developed or with individual high-risk skin cancers. Moderate reduction was considered appropriate when patients experienced > 25 skin cancers per year or for skin cancers with a 10% 3-year risk of mortality. Severe reduction was considered warranted only for life-threatening skin cancers. CONCLUSIONS: Reduction of immunosuppression is considered a reasonable adjuvant management strategy for transplant recipients with numerous or life-threatening skin cancers. Proposed guidelines are presented for the graduated reduction of immunosuppression coincident with the increasing skin cancer risks.

Investigating sun-damaged skin and actinic keratosis with optical coherence tomography: a pilot study.

Actinic Keratosis (AK) arises from sun-damaged skin and is the first clinical manifestation in the multistep process of skin carcinogenesis to invasive squamous cell carcinoma. Thus, it is an ideal target for chemopreventive efforts. Noninvasive measures of AK severity are needed to assess the efficacy of chemoprevention agents. We performed a pilot study on 20 participants to investigate the OCT appearance of sun-protected skin of the upper inner arm as well as sun-damaged skin and early AKs of the dorsal forearms, and to determine if features or quantitative measures in Optical Coherence Tomography (OCT) images could be used to reliably differentiate between these categories. OCT images of upper inner arm (normal appearing skin) showed skin layers and features (stratum corneum, epidermis, dermis, blood vessels) seen in previous studies; additionally in this participant group the subcutaneous fat layer was usually identified. Sun-damaged skin was characterized by increased signal in the epidermis and rapid attenuation of light. AKs were diverse in appearance but frequently characterized by high surface reflection, the presence of a low-signal band in the stratum corneum, and heterogeneous appearance in the epidermis/dermis. Significant differences were found between skin categories using measures of stratum corneum and epidermal/dermal depths and intensities. The presence of a dark band in the stratum corneum was 79% sensitive and 100% specific for AK. This study indicates that OCT holds promise as a useful technique for identifying and characterizing AKs and monitoring their response to chemoprevention agents.

Can Internet-based continuing medical education improve physicians' skin cancer knowledge and skills?

We sought to determine whether an Internet-based continuing medical education (CME) program could improve physician confidence, knowledge, and clinical skills in managing pigmented skin lesions. The CME program provided an interactive, customized learning experience and incorporated well-established guidelines for recognizing malignant melanoma. During a 6-week evaluation period, 354 physicians completed the on-line program as well as a pretest and an identical posttest. Use of the CME program was associated with significant improvements in physician confidence, correct answers to a 10-question knowledge test (52% vs 85% correct), and correct answers to a 15-question clinical skills test (81% vs 90% correct). We found that the overall improvement in clinical skills was due to a marked increase in specificity and a small decrease in sensitivity for evaluating pigmented lesions. User satisfaction was extremely high. This popular and easily distributed online CME program increased physicians' confidence and knowledge of skin cancer. Remaining challenges include improving the program to increase physician sensitivity for evaluating pigmented lesions while preserving the enhanced specificity.

Chemoprevention of human actinic keratoses by topical 2-(difluoromethyl)-dl-ornithine.

Alpha-2-(Difluoromethyl)-dl-ornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase, has been shown to suppress skin carcinogenesis in murine models after oral or topical administration. We designed a randomized, placebo-controlled study using a topical hydrophilic ointment formulation with or without 10% (w/w) DFMO. Forty-eight participants with moderate-severe actinic keratoses (AKs) on their forearms (i.e., at least 10 well-circumscribed lesions on the lateral surface) completed a 1-month run-in on placebo ointment. Before randomization, all lateral forearm AKs were circled, counted, photographed, and skin biopsies were obtained for DFMO and polyamine levels. Then participants were randomized to receive DFMO ointment on the right versus the left forearm and placebo hydrophilic ointment on the contralateral forearm twice daily for 6 months. DFMO was not detected in the blood of any subject, and there were no systemic toxicities. None of a subsample of 17 placebo forearms had measurable concentrations of DFMO, whereas 13 of the corresponding DFMO-treated forearms had high DFMO skin levels. As compared with placebo, the 6-month DFMO treatment caused a 23.5% reduction in the number of AKs (P = 0.001) as well as significant suppression of AK biopsy spermidine levels (26%; P = 0.04). Seven of the 48 (14.6%) participants experienced severe (2; 4.2%) or moderate (5; 10.4%) inflammatory reactions on their DFMO-treated arms which required dosing modification. Topical DFMO for 6 months can reduce the number of AK lesions and skin spermidine concentrations in high-risk participants and deserves additional study as a skin cancer chemopreventive agent.

Epidemiology of actinic keratoses and squamous cell carcinoma.

OBJECTIVE: The purpose of this article was to review the frequency, distribution, and determinants of actinic keratoses (AKs) and squamous cell carcinoma (SCC). METHODS: A review of the literature was done. RESULTS: AKs are extremely common lesions on the sun-exposed skin of Caucasian persons. The most important risk factors are a combination of genetic propensity ("fair skin phenotype") and cumulative sun exposure. Their prevalence increases with advancing age. The epidemiology of SCC is virtually the same, but the lesions occur most often on the head rather than on the upper extremities where most AKs are located. AKs are the most important risk factor identifying those most predisposed to the development of an SCC. CONCLUSION: AKs are a reliable marker for those people most predisposed to development of an invasive SCC. In addition, AKs are probably an early stage in a biologic continuum that culminates in SCC. However, there are many more AKs than SCCs, and it is difficult to predict exactly which lesions will progress to invasive cancer.

Using the Internet to teach melanoma management guidelines to primary care physicians.

The aim of this study was to determine whether a brief Internet-based education programme could improve physicians' abilities to manage pigmented skin lesions. A pre-test-post-test assessment was used of subjects' knowledge of skin cancer, confidence in their management abilities and actual ability to recommend appropriate treatment for 20 hypothetical patients with pigmented skin lesions. The setting was the general medicine service of an academic medical centre. Seventeen volunteer medical students, house officers and faculty members took part in the study. Following the pre-test, subjects completed a 1-hour computer-based educational programme, distributed via the Internet, presenting a guideline for recognizing and managing potentially malignant pigmented skin lesions. The guideline was based on the ABCD rule and the Glasgow seven-point checklist. The educational programme had a positive effect on the subjects' overall skin cancer knowledge and had significantly positive effects on their confidence and ability to apply the management guideline. Based on the guideline criteria, the subjects made the correct management decision on the clinical scenarios 63.2% of the time before the programme and 74.1% of the time after the programme (P = 0.002). We were able to teach melanoma management guidelines to physicians and medical students using a brief, interactive computer programme distributed via the Internet. Such an approach is more cost-effective than classroom teaching and could be used to improve the clinical skills of practising physicians to recognize and manage early melanomas. This approach to distributed learning could also be used to teach other clinical guidelines to physicians.

Positive surgical excision margins of a basal cell carcinoma.

This case illustrates two strongly and diametrically opposed options advocated in the literature for dealing with positive surgical margins. The best plan is to individualize the decision-making process based on the available variables (histology, location of positive margins), the patient's age and health, and a "guided," but informed decision by the patient.

Squamous cell carcinoma in a patient with chronic lymphocytic leukemia. An intraoperative diagnostic challenge for the Mohs surgeon.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is the most common form of chronic leukemia in the US. CLL patients have an increased risk of developing other malignant neoplasms, especially skin cancer. Lymphoma-associated squamous cell carcinomas (SCCs) tend to behave more aggressively and therefore are often treated with Mohs micrographic surgery (MMS). OBJECTIVE: To elucidate the potential difficulty of distinguishing perineural infiltrates as leukemic infiltrates versus inflammatory infiltrates associated with SCC on frozen tissue sections during MMS. METHODS: This is a case report illustrating a patient with CLL who develops a SCC on the posterior ear. MMS was employed to treat the patient. Special immunohistochemical stains were performed to help distinguish the type of perineural infiltrate present. RESULTS: The perineural infiltrate was shown by immunohistochemistry to be leukemic in origin. Special stains for keratin revealed no residual SCC hidden in the infiltrate. CONCLUSION: CLL is a malignancy that primarily effects the elderly population and markedly increases their risk of developing skin cancers, especially SCC. An intense infiltrate may be present surrounding the tumor. This case report demonstrates one of the potential challenges the Mohs surgeon may face in interpreting histologic frozen section. Immunohistochemistry may be helpful in providing a more definitive answer to this problem.

Correlation of histologic subtypes of primary basal cell carcinoma and number of Mohs stages required to achieve a tumor-free plane.

BACKGROUND: Certain histologic subtypes of basal cell carcinoma (BCC) behave more aggressively and require more aggressive treatment. OBJECTIVE: The aim of this study was to see whether certain subtypes of BCC require more Mohs stages to achieve tumor-free margins. METHODS: A retrospective study of 342 primary BCCs treated with Mohs micrographic surgery (MMS) was performed identifying the histologic subtype of BCC present and the number of stages required to clear the tumor. RESULTS: The aggressive subtypes (infiltrative, morpheaform, micronodular, and mixed) were most frequently found when high numbers of Mohs stages were required for cure. CONCLUSION: The more aggressive subtypes of BCC require more MMS stages to achieve tumor-free margins, which is consistent with the concept that these subtypes usually require more aggressive treatment from the start.

How to "peer review" a medical journal manuscript.

BACKGROUND: The accuracy, validity, and appropriateness of what gets published in the medical literature depends upon a pool of competent peer referees. However, the requisite skills needed to become such a peer are not taught at the residency training program level or subsequently by the journals themselves, who offer no training and little written instruction. OBJECTIVE: To outline a logical, orderly approach to the task of reviewing a "raw" medical manuscript. By breaking the overall endeavor down into smaller, step-by-step components, the novice reviewer should attain the direction and skills to complete a review with confidence. METHODS: Explore the role of the reviewer, discuss the philosophy of review, identify the key elements to look for when reading and rereading the manuscript, and outline a orderly approach to the decision making process. CONCLUSIONS: A "peer" is a physician with expertise on the subject under scrutiny who spends sufficient time and thought to fulfill two main obligations: to render an honest, unbiased decision on whether or not the manuscript should be published and, if it is acceptable, to help make it better. It is possible to perform the review process in a relatively simple, organized, and logical manner.

How to prepare and present a scientific talk. A primer.

BACKGROUND: How to organize a scientific paper and present it at a forum of one's peers is not a skill presently taught at many training programs in dermatology. OBJECTIVE: To enumerate the principles, rules, impressions, and helpful hints that will help in the preparation and delivery of a scientific talk. METHODS: An attempt has been made, from the authors experience, to assimilate and codify the requisite organizational and delivery skills necessary to accomplish this. CONCLUSIONS: Organization must begin early. The key is to keep in mind that new information is being conveyed to the audience. The speaker must prepare an outline, develop visual aids, and rehearse diligently to hone speaking skills and ensure the talk is within time parameters.

Nonsurgical treatment of basal cell carcinomas with intralesional 5-fluorouracil/epinephrine injectable gel.

BACKGROUND: To develop a nonsurgical treatment alternative for basal cell carcinomas (BCCs), we evaluated intralesional sustained-release chemotherapy with 5-fluorouracil/epinephrine injectable gel (5-FU/epi gel). OBJECTIVE: To optimize the dose and treatment schedule, we compared the safety, tolerance, and efficacy of six treatment regimens of 5-FU/epi gel in patients with BCCs. METHODS: Two doses and four treatment schedules of 5-FU/epi gel were compared in an open-label, randomized study of 122 patients with biopsy-proven BCCs. One BCC per patient was treated for up to 4 to 6 weeks, then observed for 3 months at which time the tumor site was completely excised for histologic examination. RESULTS: Overall, 91% of evaluable treated tumors (106 of 116) in all regimens had histologically confirmed complete tumor resolution. No clinically significant treatment-related systemic adverse events occurred. The best response rate, tolerance, and patient compliance with assigned dose were in patients receiving 0.5 ml of 5-FU/epi gel three times a week for 2 weeks. The complete response rate based on histologic assessment in this group was 100%. CONCLUSION: Results demonstrate that treatment of BCC with 5-FU/epi gel is both safe and effective, may result in histologically confirmed complete response rates comparable to surgery, and provides a nonsurgical treatment alternative in selected patients.