Multiple Cutaneous Cancers in an Interventional Cardiologist: Predominance in Unprotected Skin Nearest the Radiation Source.

A 70 year-old interventional cardiologist, who worked in the cardiac catheterization laboratory for >35 years, developed multiple skin cancers in regions not conventionally covered by protective lead apparel. The majority of lesions were left-sided, representing cutaneous regions in closest proximity to the radiation source. Although skin not covered by lead apparel often receives frequent sun exposure, a known risk factor for skin cancer, malignancies resulting exclusively from sun exposure would not in most cases be expected to have a left-sided predominance. Additional research is warranted to study the potential link between occupational radiation exposure and skin cancer risk.

Intraepidermal erbium:YAG laser resurfacing: impact on the dermal matrix.

BACKGROUND: Various minimally invasive treatments enhance the skin's appearance. Little is known about the molecular mechanisms whereby treatments working at the epidermal level might alter the dermis. OBJECTIVE: We sought to quantify the molecular changes that result from erbium:yttrium-aluminium-garnet (Er:YAG) laser microablative resurfacing. METHODS: We performed biochemical analyses after intraepidermal Er:YAG laser resurfacing of 10 patients. Immunohistochemical analysis and polymerase chain reaction technology were utilized to measure key biomarkers. RESULTS: The basement membrane remained intact after intraepidermal microablation, as demonstrated by laminin γ2 immunostaining. Epidermal injury was demonstrated with acute up-regulation of keratin 16. An inflammatory response ensued as indicated by increases in cytokines interleukin 1 beta (IL-1ß) and IL-8 as well as a substantial neutrophil infiltrate. Levels of cJun and JunB proteins, components of the transcription factor AP-1 complex, were also elevated. Up-regulation of extracellular matrix degrading proteinases matrix metalloproteinase 1 (MMP-1), MMP-3, and MMP-9 was noted. A transient increase in keratinocyte proliferation, as indicated by staining for Ki67, was observed. Increased expression of type I and type III procollagen was demonstrated. LIMITATIONS: The data presented are those that resulted from a single treatment session. CONCLUSIONS: Although microablation was confined to the uppermost epidermis, marked changes in epidermal and dermal structure and function were demonstrated after Er:YAG laser microablative resurfacing. We demonstrated substantial dermal matrix remodeling, including a degree of collagen production that compares favorably with some more invasive interventions. Dermal remodeling and stimulation of collagen production are associated with wrinkle reduction. Thus these results suggest that the skin's appearance may be enhanced by creating dermal changes through the use of superficially acting treatments.

Microdermabrasion: an evidence-based review.

Microdermabrasion is a popular technique used in the treatment of several skin problems, including acne, acne scarring, striae distensae, and photoaging. This article will review the relevant literature and use an evidence-based approach to evaluate the clinical efficacy of microdermabrasion in skin care. In summary, microdermabrasion appears to be a procedure that can produce changes in dermal matrix constituents and result in improvement in skin contour irregularities. It may also be beneficial in improving transepidermal delivery of certain medications. Its role in the treatment of dyschromias and acne vulgaris is limited.

Molecular analysis of aggressive microdermabrasion in photoaged skin.

OBJECTIVE: To investigate dermal remodeling effects of crystal-free microdermabrasion on photodamaged skin. DESIGN: Biochemical analyses of human skin biopsy specimens following microdermabrasion treatment in vivo. SETTING: Academic referral center. PARTICIPANTS: Volunteer sample of 40 adults, aged 50 to 83 years, with clinically photodamaged forearms. Intervention Focal microdermabrasion treatment with diamond-studded handpieces of varying abrasiveness on photodamaged forearms and serial biopsies at baseline and various times after treatment. MAIN OUTCOME MEASURES: Quantitative polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay were used to quantify changes in inflammatory, proliferative, and remodeling effectors of normal wound healing. Type I and type III procollagen served as the main outcome marker of dermal remodeling. RESULTS: Coarse-grit microdermabrasion induces a wound healing response characterized by rapid increase in induction of cytokeratin 16 and activation of the AP-1 transcription factor in the epidermis. Early inflammation was demonstrated by induction of inflammatory cytokines, antimicrobial peptides, and neutrophil infiltration in the dermis. AP-1 activation was followed by matrix metalloproteinase-mediated degradation of extracellular matrix. Consistent with this wound-healing response, we observed significant remodeling of the dermal component of the skin, highlighted by induction of type I and type III procollagen and by induction of collagen production enhancers heat shock protein 47 and prolyl 4-hydroxylase. Dermal remodeling was not achieved when microdermabrasion was performed using a medium-grit handpiece. CONCLUSIONS: Microdermabrasion using a coarse diamond-studded handpiece induces a dermal remodeling cascade similar to that seen in incisional wound healing. Optimization of these molecular effects is likely the result of more aggressive treatment with a more abrasive handpiece.

Topical fluorouracil for actinic keratoses and photoaging: a clinical and molecular analysis.

OBJECTIVE: To examine clinical and molecular changes after topical fluorouracil treatment of photodamaged human facial skin for actinic keratoses. DESIGN: Nonrandomized, open-label 2-week treatment with fluorouracil cream, 5%, followed by clinical and molecular evaluation. SETTING: Academic referral center. PATIENTS: Twenty-one healthy volunteers, 56 to 85 years old, with actinic keratoses and photodamage. Interventions Twice-daily application of fluorouracil cream for 2 weeks and biopsies and clinical evaluation at baseline and periodically after treatment. MAIN OUTCOME MEASURES: Gene and protein expression of molecular effectors of epidermal injury, inflammation, and extracellular matrix remodeling 24 hours after fluorouracil treatment; clinical improvement measured by evaluators, photography, and patient questionnaires. RESULTS: One day after the final fluorouracil treatment, gene expression of the effectors of epidermal injury (keratin 16), inflammation (interleukin 1beta), and extracellular matrix degradation (matrix metalloproteinases 1 and 3) was significantly increased. Types I and III procollagen messenger RNA were induced at week 4 (7-fold and 3-fold, respectively). Type I procollagen protein levels were increased 2-fold at week 24. Actinic keratoses and photoaging were statistically significantly improved. Most patients rated photoaging as improved and were willing to undergo the therapy again. CONCLUSIONS: Topical fluorouracil causes epidermal injury, which stimulates wound healing and dermal remodeling resulting in improved appearance. The mechanism of topical fluorouracil in photoaged skin follows a predictable wound healing pattern of events reminiscent of that seen with laser treatment of photoaging.

A randomized, controlled, split-face clinical trial of 1320-nm Nd:YAG laser therapy in the treatment of acne vulgaris.

BACKGROUND: There is a need for additional effective treatments for acne vulgaris. Laser therapy has been explored as a therapeutic option for acne, but rigorously designed studies in this area have been limited. OBJECTIVE: We sought to examine the efficacy of an infrared laser in the treatment of acne. METHODS: We conducted a randomized, controlled, single-blind, split-face clinical trial of 46 patients with facial acne. Patients received a series of 3 nonablative laser treatments using a novel neodymium:yttrium-aluminum-garnet (Nd:YAG) laser to half of the face. Serial blinded lesion counts and global acne severity rating of standardized bilateral patient photographs were performed. Sebum production was measured, and patient self-assessment surveys were administered. RESULTS: A transient but statistically significant improvement in lesion counts of open comedones was demonstrated in treated skin as compared with untreated skin. There were no significant differences between treated and control sides of the face in terms of changes in mean papule or pustule counts. Grading of serial photographs revealed no significant differences between treated and untreated skin. Patient surveys indicated that the majority of patients found the treatments to be at least mildly effective for both acne and oiliness. LIMITATIONS: The current study only addresses the efficacy of a single laser system employing a specific treatment regimen. CONCLUSIONS: Infrared laser therapy may improve comedonal acne. Additional work is needed to better define the degree and duration of the effect. Patients appear to positively view such therapy for both acne and oily skin.

Microdermabrasion with and without aluminum oxide crystal abrasion: a comparative molecular analysis of dermal remodeling.

BACKGROUND: Microdermabrasion is a popular method of superficial skin resurfacing with effects on dermal remodeling. OBJECTIVE: The purpose of this study was to evaluate the relative importance of the two components of microdermabrasion, negative pressure and abrasion, in stimulating expression of key genes involved in dermal remodeling. METHODS: Ten subjects were treated with a microdermabrasion machine using focal crystal abrasion and negative pressure or negative pressure alone for 3 seconds. Serial biochemical analyses were performed. Reverse transcriptase real-time polymerase chain reaction assays were used to evaluate changes in transcription factor activator protein-1, primary cytokines (interleukin 1beta, tumor necrosis factor-alpha), and matrix metalloproteinases (MMP-1, MMP-3, MMP-9). RESULTS: Significant increases in gene expression of the c-Jun component of activator protein-1, interleukin 1beta, tumor necrosis factor-alpha, MMP-1, MMP-3, and MMP-9 were found with crystal abrasion combined with negative pressure. Negative pressure alone resulted in increased gene expression of MMP-1 and MMP-3 but of a quantitatively reduced magnitude when compared with negative pressure with crystal abrasion. LIMITATIONS: It is unclear that molecular changes seen with these treatments can result in clinical effect. CONCLUSION: The abrasive component of microdermabrasion is necessary for stimulating expression of key genes involved in dermal remodeling.

Dermal matrix remodeling after nonablative laser therapy.

OBJECTIVE: Nonablative laser therapy is widely practiced for cutaneous rejuvenation. We sought to quantify dermal molecular changes after exposure of photodamaged skin to nonablative laser energy. METHODS: Nonablative laser therapy of forearm skin using either a 585-nm wavelength pulsed dye laser or a 1320-nm wavelength neodymium:yttrium-aluminum-garnet laser was performed. Serial biopsy specimens were obtained at baseline and various times after treatment. RESULTS: Statistically significant increases in type I procollagen messenger RNA expression occurred after exposure of photodamaged skin to each laser. Induction was 47% (P < .05) and 84% (P < .05) above baseline levels 1 week after laser therapy among those treated with the pulsed dye and neodymium:yttrium-aluminum-garnet lasers, respectively. Substantial induction of type III procollagen, various matrix metalloproteinases, and primary cytokines was also demonstrated. Responses with respect to all molecules studied were highly variable. LIMITATIONS: This study addresses molecular changes after a single laser exposure whereas clinically, serial treatments are often provided. CONCLUSIONS: Nonablative laser therapy may result in quantifiable alterations in molecules associated with remodeling of the dermal matrix, although responses vary greatly among patients.

The effects of a professionally produced videotape on education and anxiety/distress levels for patients with newly diagnosed melanoma: a randomized, prospective clinical trial.

OBJECTIVE: Little is known about the effects of videotape-based education on knowledge and anxiety levels among patients with melanoma. We sought to evaluate effects of a professionally produced videotape on the knowledge and distress levels among patients with newly diagnosed melanoma. Secondarily, we sought to compare these effects with those of a traditional clinic visit. METHODS: We conducted a randomized controlled trial involving 217 patients. An intervention group underwent questionnaire-based testing of melanoma knowledge and anxiety/distress levels before and after viewing an educational videotape. A control group underwent similar testing before and after a clinic visit. RESULTS: The videotape and clinical encounter significantly increased knowledge and decreased anxiety. Improvement in knowledge levels was significantly greater after viewing the videotape compared with the clinic visit, whereas anxiety levels decreased to a greater degree after the clinical encounter. Whether or not a synergistic relationship may exist between exposure to an educational videotape and a physician visit was not specifically evaluated in this study. CONCLUSION: Videotape-based education may be more effective than that provided by a clinic visit, whereas the clinical encounter appears to be more effective in alleviating patient anxiety/distress.

Patterns of Internet use and impact on patients with melanoma.

BACKGROUND: Patients with cancer and their families frequently, and increasingly, turn to outside sources for information, particularly the World Wide Web. Our objective was to examine the use of the Internet and its impact among patients with melanoma. METHODS: A prospective survey was obtained from 1613 consecutive patients with cutaneous melanoma seen at our institution between August 2001 and February 2003. Main outcome measures included the ability to access the Internet, Internet use to search for melanoma information, and responses to such Internet searches. Further analysis of whether there were differences based on age, sex, or disease severity was performed. RESULTS: Of patients with melanoma, 39% indicated that they had used the Internet to research their disease, 30% themselves and 9% had someone else do it for them. Nearly half (47%) of patients younger than 40 years researched melanoma on the Internet compared with only 12% of patients 60 years or older. Neither sex nor disease severity impacted Internet use. The vast majority of patients (94%) thought the Internet was useful, 67% believed it helped them better understand their condition, and 45% said they would recommend using the Internet to others to find information about medical conditions. Roughly a third thought it decreased their anxiety, whereas a similar proportion believed the Internet made them more anxious. Increased anxiety correlated with decreasing age and increasing disease severity. CONCLUSIONS: The use of the Internet is common among patients with melanoma. Anxiety attributed to online information about their disease suggests that clinicians caring for patients with melanoma should familiarize themselves with online melanoma information, and be proactive in assisting their patients in using this resource.

Microstaging accuracy after subtotal incisional biopsy of cutaneous melanoma.

BACKGROUND: A significant portion of cutaneous melanoma may remain after subtotal incisional biopsy. The accuracy of microstaging and impact on clinical practice in this scenario are unknown. OBJECTIVE: Our purpose was to examine microstaging accuracy of an initial incisional biopsy with a significant portion of the clinical lesion remaining (> or =50%). METHODS: Patients with cutaneous melanoma, diagnosed by incisional biopsy with > or =50% of the lesion remaining, were prospectively evaluated for microstaging accuracy, comparing initial Breslow depth (BD1) to final depth (BD2) after excision of the residual lesion. Impact on prognosis and treatment was also evaluated. RESULTS: Two hundred fifty of 1783 patients (14%) presented with > or =50% residual clinical lesion after incisional biopsy. The mean BD1 was 0.66 mm; the mean BD2, 1.07 mm (P = .001). After complete excision of the residual lesion, upstaging occurred in 21% and 10% became candidates for sentinel node biopsy. CONCLUSION: An incisional biopsy with > or =50% clinical lesion remaining afterward may be inadequate for accurate microstaging of melanoma. This scenario is relatively uncommon but clinically significant.

Microdermabrasion: a molecular analysis following a single treatment.

BACKGROUND: Microdermabrasion is a popular method of superficial skin resurfacing. It is unclear if dermal remodeling actually occurs. OBJECTIVE: To rigorously investigate the molecular alterations observed following a single microdermabrasion treatment. METHODS: Forty-nine subjects received a single microdermabrasion treatment to buttock skin. Serial in vivo biochemical and immunohistological analyses were performed. Reverse transcriptase real-time polymerase chain reaction and immunohistochemistry assays were used to evaluate changes in transcription factors (AP-1, NF-kappaB), primary cytokines (interleukin-1beta, tumor necrosis factor-alpha), matrix metalloproteinases (MMP-1, MMP-3, MMP-9), barrier repair enzymes (acetyl-coenzyme A carboxylase, 3-hydroxy-3-methylglutaryl coenzyme A reductase), and type I procollagen. Results Elevation of transcription factors, primary cytokines, and matrix metalloproteinases occurs rapidly after a single microdermabrasion treatment. Two of 11 subjects also demonstrated increased type I procollagen messenger RNA and protein levels 14 days after treatment. No alteration in stratum corneum thickness was detected. CONCLUSION: Microdermabrasion activates a dermal remodeling/wound healing cascade with minimal epidermal disruption. Evidence now exists to further study manipulation of variables such as number and timing of microdermabrasion sessions.

Tretinoin treatment before carbon-dioxide laser resurfacing: a clinical and biochemical analysis.

BACKGROUND: Tretinoin is often prescribed before laser resurfacing in an attempt to enhance results. OBJECTIVE: We sought to assess the clinical and biochemical effects of preoperative tretinoin use before laser resurfacing. METHODS: Patients were randomized to apply tretinoin to one forearm and placebo to the other for 3 weeks. Patients' photodamaged forearms were focally treated by carbon-dioxide laser resurfacing. Biopsy specimens were obtained at baseline and various times posttreatment. Real-time polymerase chain reaction technology was used to quantify messenger RNA levels of types I and III procollagen and matrix metalloproteinases-1, 3, and 9. Wounds were assessed for degree of re-epithelialization using a computer graphics-generated template. A colorimeter was used to quantify postoperative erythema. RESULTS: No substantial differences in either biochemical markers or clinical end points were identified between tretinoin and placebo pretreated forearms. CONCLUSIONS: We found no evidence of enhanced collagen formation, accelerated re-epithelialization, or quicker resolution of postoperative erythema with tretinoin pretreatment before laser resurfacing.

Connective tissue remodeling induced by carbon dioxide laser resurfacing of photodamaged human skin.

OBJECTIVE: To quantitatively examine the dynamics of molecular alterations involved in dermal remodeling after carbon dioxide (CO(2)) laser resurfacing of photodamaged human skin. DESIGN: Serial in vivo biochemical analyses after laser therapy. SETTING: Academic referral center, Department of Dermatology, University of Michigan, Ann Arbor. Subjects Volunteer sample of 28 adults, 48 to 76 years old, with clinically evident photodamage of the forearms. Intervention Focal CO(2) laser resurfacing of photodamaged forearms and serial biopsies at baseline and various times after treatment. MAIN OUTCOME MEASURES: Reverse transcriptase real-time polymerase chain reaction technology and immunohistochemistry were used to assess levels of type I and type III procollagens; matrix metalloproteinases (MMPs) 1, 3, 9, and 13; tropoelastin; fibrillin; primary cytokines interleukin 1beta and tumor necrosis factor alpha; and profibrotic cytokine transforming growth factor beta1. RESULTS: Production of type I procollagen and type III procollagen messenger RNA peaked at 7.5 and 8.9 times baseline levels, respectively, 21 days after treatment and remained elevated for at least 6 months. Increases in messenger RNA levels of several cytokines (interleukin 1beta, tumor necrosis factor alpha, and transforming growth factor beta1) preceded and/or accompanied changes in collagen levels. Marked increases in messenger RNA levels of MMP-1 (39 130-fold), MMP-3 (1041-fold), MMP-9 (75-fold), and MMP-13 (767-fold) were noted. Levels of fibrillin and tropoelastin rose in a delayed fashion several weeks after treatment. CONCLUSIONS: The biochemical changes seen after CO(2) laser resurfacing proceed through a well-organized and highly reproducible wound healing response that results in marked alterations in dermal structure. These quantitative changes may serve as a means for comparison as other therapeutic modalities meant to improve the appearance of photodamaged skin are evaluated.

An education theory-based method to teach a procedural skill.

OBJECTIVE: To determine the effectiveness of an education theory-based method to teach students to place and tie a simple interrupted stitch. DESIGN: A teaching intervention before-after trial. SETTING: Dermatology department, academic university. PARTICIPANTS: Fourth-year medical students and dermatology residents. MAIN OUTCOME MEASURES: Scores on a 12-criterion grading instrument before and after instruction. RESULTS: The scores for medical students and residents in each class showed significant improvement. The mean score for all participants (N = 23) rose by 24% after instruction (P< .001). Scores in 9 of the 12 graded performance areas improved significantly after instruction, including scores in tissue damage/teeth marks (P<.001), needle dulled/bent (P< .001), needle loaded properly and knots square (P = .01), throws done correctly (P = .01), stitch tension and needle entry/exit angle (P = .02), amount of suture used (P = .03), and correct number of throws (P = .04). In addition, participants' confidence increased significantly after instruction (P<.001). No difference was noted between men and women in preinstruction vs postinstruction score improvement. CONCLUSIONS: This teaching method can be effectively used to teach students to place and tie a simple interrupted stitch. Once validated and expanded, it may prove useful in shortening and standardizing procedural skill training and in objectively documenting competency.

Effect of carbon dioxide laser resurfacing on epidermal p53 immunostaining in photodamaged skin.

OBJECTIVE: To quantitatively examine changes in p53 tumor suppressor gene immunostaining after carbon dioxide (CO(2)) laser resurfacing of photodamaged skin to assess the potential value of this treatment in reducing the risk of progression to cutaneous carcinoma. DESIGN: Serial in vivo immunohistochemical analyses after laser therapy. SETTING: Academic referral center, Department of Dermatology, University of Michigan, Ann Arbor. OTHER PARTICIPANTS: Volunteer sample of 11 adults, 51 to 76 years old, with clinically evident photodamage of the forearms. INTERVENTION: Focal CO(2) laser resurfacing of photodamaged forearms and serial biopsies at baseline, 3 weeks, and 6 months after treatment. MAIN OUTCOME MEASURES: Because keratinocytes with mutations in p53 or altered p53 expression stain via immunohistochemical techniques, image analysis of immunohistochemically stained sections was used to quantify p53 expression. RESULTS: Positive immunostaining for p53 in the interfollicular epidermis was noted in 8 of 11 subjects at baseline, with an average staining density of 250 cells/mm(2). Average staining decreased to 3 cells/mm(2) 3 weeks after treatment. This decrease was sustained at 5 cells/mm(2) 6 months after resurfacing. CONCLUSIONS: There was a consistent decrease in p53 immunostaining in the interfollicular epidermis lasting for at least 6 moths after CO(2) laser resurfacing of photodamaged skin. Since p53 mutation or overexpression is observed in a majority of cases of cutaneous carcinoma, the posttreatment repopulation of the epidermis with p53-negative keratinocytes should theoretically decrease the risk of malignant progression. Further study of laser resurfacing as a prophylactic procedure in patients at high risk for skin cancer development appears warranted.

Treatment of acne vulgaris with a pulsed dye laser: a randomized controlled trial.

CONTEXT: The high prevalence of acne vulgaris and its significant morbidity underscore the need for convenient, low-risk, and efficacious therapy. Treatment with various lasers has been reported to improve acne. OBJECTIVE: To evaluate the clinical efficacy of pulsed dye laser therapy in the treatment of acne. DESIGN, SETTING, AND PATIENTS: Randomized, single-blind, controlled, split-face clinical trial of a volunteer sample of 40 patients aged 13 years or older with facial acne conducted at an academic referral center from August 2002 to September 2003. INTERVENTION: One or 2 nonpurpuric pulsed dye laser treatments to half of the face (fluence of 3 J/cm2), serial blinded clinical assessments (lesion counts), and grading of acne severity using standardized bilateral serial photographs. MAIN OUTCOME MEASURES: Comparison of the changes in lesion counts from baseline to 12 weeks between treated and untreated sides of the face and changes in photographic evidence of acne severity as graded by a panel of dermatologists blinded to treatment assignment. RESULTS: After 12 weeks, using intent-to-treat analysis with last observation carried forward, there were no significant differences between laser-treated and untreated skin for changes in mean papule counts (-4.2 vs -2.2; P =.08), mean pustule counts (0 vs -1.0; P =.12), or mean comedone counts (2.9 vs 1.6; P =.63). Grading of serial photographs confirmed the clinical assessments, showing no significant mean (SE) differences in Leeds scores (range, 1-12) for treated skin (3.98 [0.32] at baseline and 3.94 [0.27] at week 12) compared with untreated skin (3.83 [0.32] at baseline and 3.79 [0.28] at week 12) (P>.99). CONCLUSIONS: In this study, the nonpurpuric pulsed dye laser therapy did not result in significant improvement of facial acne. More research is needed before this laser therapy may be recommended as an acne treatment.

Standard immunostains for melanoma in sentinel lymph node specimens: which ones are most useful?

BACKGROUND: Sentinel lymph node (SLN) biopsy in melanoma is an increasingly used procedure. Pathologic evaluation of SLNs using immunohistochemistry improves diagnostic accuracy, yet no universally accepted standard protocol for pathologic processing of SLNs exists. OBJECTIVE: The primary purpose of this study was to evaluate our experience with the sensitivity of the immunostains S-100, HMB-45, and Melan-A for SLN biopsy. METHODS: Ninety-nine positive SLNs from 72 patients were retrospectively reviewed for the presence of microscopic metastatic melanoma on hematoxylin and eosin (H&E), S-100, HMB-45, and Melan-A stained sections and sensitivities of each immunohistochemical stain were determined. RESULTS: The sensitivities of S-100, HMB-45, and Melan-A were 97%, 75%, and 96% respectively. CONCLUSION: Given the lower sensitivity of HMB-45, our practice for evaluation of SLN biopsy specimens was modified using combinations of H&E, S-100, and Melan-A without HMB-45. If the H&E sections are negative or equivocal for metastatic melanoma, immunohistochemistry staining with S-100 protein and Melan-A is performed. New and improved protocols will undoubtedly be forthcoming as the field advances.