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Background: Published rates of cutaneous multiple primary melanoma (MPM) vary widely., Objective: We examined incidence of and risk factors associated with MPMs among Kaiser Permanente Northern California members., Methods: We estimated MPM incidence among 16,570 patients with melanoma from 1996 through 2011. We compared characteristics between patients with MPMs and single primary melanomas and estimated crude and adjusted hazard ratios of MPMs using Cox models., Results: In all, 15,448 patients had a single melanoma and 1122 had MPMs. Patients with MPMs were older and more often male, non-Hispanic white, and partnered. Subsequent primary melanomas were diagnosed after a mean of 3.83 (SD 3.61, median 2.82) years and were more likely in situ and thinner than initial tumors. The risk of a subsequent melanoma decreased from 2% in the first year after diagnosis to a stable approximately 1% rate through 15 years of follow-up., Limitations: We lacked data on some known melanoma risk factors and had small numbers of non-white patients and certain tumor subtypes., Conclusions: The risk of MPMs, although highest in the first year after diagnosis, remains stable thereafter. Those at highest risk of MPMs are older, male, white, and partnered. Clinicians should be aware of the rate of MPMs and recognize high-risk subgroups., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Little is known about the use of sirolimus for primary prevention of cutaneous squamous cell carcinoma (SCC) among solid organ transplant recipients (SOTRs)., Objective: We examined the association between sirolimus exposure and incident SCC risk among SOTRs within Kaiser Permanente Northern California., Methods: Using a retrospective cohort of all Kaiser Permanente Northern California members given a diagnosis of SOTR from 2000 through 2010, we evaluated incident posttransplantation SCC risk in relation to sirolimus exposure. Sirolimus use was determined from electronic pharmacy records, and incident posttransplantation SCCs were identified from health plan electronic pathology records. We used extended Cox regression to examine the independent association between receipt of sirolimus and risk of SCC., Results: Among 3539 SOTRs, 488 were exposed to sirolimus and 47 developed an incident SCC. SCC risk was not associated with ever use of sirolimus (adjusted hazard ratio 1.18, 95% confidence interval 0.84-1.16) or cumulative duration of sirolimus exposure (adjusted hazard ratio 2.75, 95% confidence interval 0.84-9.04, comparing long-term users with nonusers)., Limitations: No information was available for some known SCC risk factors, such as skin type and sun exposure., Conclusions: Among a large cohort of SOTRs, sirolimus exposure was not associated with a reduction in incident posttransplantation SCC risk., (Copyright © 2015 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.)

Importance: The incidence of basal cell carcinomas (BCCs) is increasing globally, but incidence rates in the United States are difficult to quantify because BCCs are not reportable tumors., Objective: To estimate annual BCC incidence rates by age, sex, and race/ethnicity to identify demographically distinct high-risk subgroups and to assess changes in rates over time., Design, Setting, and Participants: In this retrospective cohort study (January 1, 1998, through December 31, 2012), we studied 147 093 patients with BCC from Kaiser Permanente Northern California, a large, integrated health care provision system, identified using a previously validated BCC registry., Main Outcomes and Measures: We estimated annual BCC incidence rates by age, sex, and race/ethnicity and assessed changes in rates over time. The BCC incidence rates were standardized to the age, sex, and race/ethnicity distribution of the 2010 US Census population., Results: In models adjusting for age, sex, and race, male patients had higher rates than female patients (incidence rate ratio [IRR], 1.65; 95% CI, 1.60-1.70). Persons 65 through 79 years of age and those 80 years and older had higher rates than persons 40 through 64 years of age (IRR, 2.96; 95% CI, 2.86-3.06; and IRR, 5.14; 95% CI, 4.94-5.35, respectively). Whites had higher rates than multiracial persons (IRR, 1.96; 95% CI, 1.80-2.13), Hispanics (IRR, 8.56; 95% CI, 7.79-9.41), Asians (IRR, 33.13; 95% CI, 27.84-39.42), and blacks (IRR, 72.98; 95% CI, 49.21-108.22)., Conclusions and Relevance: We estimate that BCCs occur in approximately 2 million Americans annually. Our findings provide an updated estimate of the incidence of BCCs, highlight the changing epidemiologic findings, and better identify demographically distinct high-risk subgroups.

Background: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) carry a high mortality risk. While identifying clinical and genetic risk factors for these conditions has been hindered by their rarity, large electronic health databases hold promise for identifying large numbers of cases for study, especially with the introduction in 2008 of ICD-9 codes more specific for these conditions., Objective: The objective of this study is to estimate the validity of ICD-9 codes for ascertaining SJS/TEN in 12 collaborating research units in the USA, covering almost 60 million lives., Methods: From the electronic databases at each site, we ascertained potential cases of SJS/TEN using ICD-9 codes. At five sites, a subset of medical records was abstracted and standardized criteria applied by board-certified dermatologists to adjudicate diagnoses. Multivariate logistic regression was used to identify factors independently associated with validated SJS/TEN cases., Results: A total of 56 591 potential cases of SJS/TEN were identified. A subset of 276 charts was selected for adjudication and 39 (of the 276) were confirmed as SJS/TEN. Patients with the ICD-9 codes introduced after 2008 were more likely to be confirmed as cases (OR 3.32; 95%CI 0.82, 13.47) than those identified in earlier years. Likelihood of case status increased with length of hospitalization. Applying the probability of case status to the 56 591 potential cases, we estimated 475-875 to be valid SJS/TEN cases., Conclusion: Newer ICD-9 codes, along with length of hospitalization, identified patients with a high likelihood of SJS/TEN. This is important for identification of subjects for future pharmacogenomics studies., (Copyright © 2015 John Wiley & Sons, Ltd.)

Background: The contribution of family history to cutaneous squamous cell carcinoma (SCC) risk has not been systematically quantified., Objective: To examine the association between self-reported family history of skin cancer and SCC risk., Methods and Materials: Cases (n = 415) with a pathology-verified SCC and 415 age-, gender-, and race-matched controls were identified within a large integrated health care delivery system. Family history and skin cancer risk factors were ascertained by survey. Odds ratios (ORs) for associations of SCC with family history of skin cancer were estimated using conditional logistic regression adjusted for environmental and innate SCC risk factors., Results: Any known family history of skin cancer was associated with a four-fold higher risk of SCC, adjusting for known environmental and innate SCC risk factors (OR, 4.0; confidence interval [CI]: 2.5-6.5). An unknown family history of skin cancer showed similar risk for SCC (OR, 3.9; CI: 2.4-6.5). In models including skin cancer type, the strongest association was for family history of basal cell carcinoma (OR, 9.8; CI: 2.6-36.8) and for multiple skin cancer types (OR, 10.5; CI: 3.7-29.6)., Conclusion: Family history of skin cancer is an important independent risk factor for cutaneous SCCs.

An efficient approach to characterizing the disease burden of rare genetic variants is to impute them into large well-phenotyped cohorts with existing genome-wide genotype data using large sequenced referenced panels. The success of this approach hinges on the accuracy of rare variant imputation, which remains controversial. For example, a recent study suggested that one cannot adequately impute the HOXB13 G84E mutation associated with prostate cancer risk (carrier frequency of 0.0034 in European ancestry participants in the 1000 Genomes Project). We show that by utilizing the 1000 Genomes Project data plus an enriched reference panel of mutation carriers we were able to accurately impute the G84E mutation into a large cohort of 83,285 non-Hispanic White participants from the Kaiser Permanente Research Program on Genes, Environment and Health Genetic Epidemiology Research on Adult Health and Aging cohort. Imputation authenticity was confirmed via a novel classification and regression tree method, and then empirically validated analyzing a subset of these subjects plus an additional 1,789 men from Kaiser specifically genotyped for the G84E mutation (r2 = 0.57, 95% CI = 0.37–0.77). We then show the value of this approach by using the imputed data to investigate the impact of the G84E mutation on age-specific prostate cancer risk and on risk of fourteen other cancers in the cohort. The age-specific risk of prostate cancer among G84E mutation carriers was higher than among non-carriers. Risk estimates from Kaplan-Meier curves were 36.7% versus 13.6% by age 72, and 64.2% versus 24.2% by age 80, for G84E mutation carriers and non-carriers, respectively (p = 3.4x10-12). The G84E mutation was also associated with an increase in risk for the fourteen other most common cancers considered collectively (p = 5.8x10-4) and more so in cases diagnosed with multiple cancer types, both those including and not including prostate cancer, strongly suggesting pleiotropic effects. [corrected].

Objectives: Intratumoral CD8+ lymphocytes (IT-CD8s) have shown promise as a prognostic indicator for Merkel cell carcinoma (MCC). We tested whether IT-CD8s predict survival among a population-based MCC cohort., Methods: One hundred thirty-seven MCC cases that had not previously been analyzed for IT-CD8s were studied., Results: Three-year MCC-specific survival rates were 56%, 72%, and 100% for patients with absent (n = 46), low (n = 85), and moderate or strong (n = 6) IT-CD8s, respectively. Increased IT-CD8s were associated with improved MCC-specific survival in a multivariate competing risk-regression analysis including stage, age, and sex (hazard ratio [HR] = 0.5; 95% confidence interval [CI] = 0.3-0.9). Although a similar trend was observed for overall survival, statistical significance was not reached (HR = 0.8; 95% CI = 0.6-1.0), likely because of the high rate of non-MCC deaths among older patients., Conclusions: This study of prospectively captured MCC cases supports the concept that cellular immunity is important in MCC outcome and that CD8+ lymphocyte infiltration adds prognostic information to conventional staging., (Copyright© by the American Society for Clinical Pathology.)

Background: Psoriasis may predispose to cardiovascular disease and diabetes. However, the role of tumor necrosis factor (TNF) inhibitor in mediating this risk is controversial., Objective: To assess this relationship, we estimated change in metabolic physiologic measures before and after initiation of TNF inhibitor therapy compared with methotrexate (MTX) therapy among psoriasis patients., Methods: We conducted a retrospective cohort study, 2007-2012, using computerized clinical data for 1274 new users of TNF inhibitor and 979 new users of MTX therapy to compare change in blood pressure, lipids, triglycerides, fasting plasma glucose and body mass index (BMI) before and after start of TNF inhibitors or MTX. The study was restricted to new users. We computed within-person change in each measure, so that each patient served as their own control. In addition, we compared TNF inhibitor patients to MTX patients, by computing the adjusted difference in their group means. In secondary analyses, we examined phototherapy as a comparator., Results: Among starters of TNF inhibitor and MTX therapy, within-person change in physiologic measures at 6 months did not differ significantly. We observed no important or significant changes in any of the physiologic measures with initiation of TNF inhibitor compared with MTX. The same results were found in subgroup analyses focused on men, and on those with hypertension, diabetes mellitus, or obesity. The same results were observed with phototherapy, except that diastolic blood pressure declined by 0.6 mmHg within person during the 6 months after starting phototherapy (P < 0.05)., Conclusions: The study provides no evidence for improvement of physiologic measures associated with the metabolic syndrome resulting from TNF inhibitor use for psoriasis., (© 2013 European Academy of Dermatology and Venereology.)

Supplement use is prevalent, and its use is increasing among older adults. Dermatologists need to be aware of the adverse cutaneous effects that can result from herbal supplement use. A 55-year-old man presented with an eruption in a sebotropic distribution after consuming kava kava for 3 weeks, which resolved after discontinuation of the supplement. This case highlights the need for clinicians to consider kava kava in the differential of sebotropic eruptions. The biology, mechanism of action, and potential systemic and cutaneous effects of kava kava are reviewed., (© 2014 British Association of Dermatologists.)

Background: Patients with melanoma are at increased risk for cutaneous squamous cell carcinomas (SCCs)., Objective: We sought to examine the incidence of subsequent SCC among melanoma survivors and the impact of patient and melanoma characteristics on SCC risk., Methods: Kaiser Permanente Northern California members given the diagnosis of melanoma from 2000 to 2005 (n = 6378) were followed up through 2009 for a pathology-confirmed SCC. Cox models were used to estimate SCC risk., Results: The crude SCC incidence rate was 2.41 per 100 person-years, and was higher among males and older subjects. In adjusted models stratified by age, SCC risk was higher among males (hazard ratio [HR] 1.43, 95% confidence interval [CI] 1.22-1.67), those with history of nonmelanoma skin cancer (HR 2.56, 95% CI 2.19-2.98), and those with higher tumor sequence numbers (HR 1.35, 95% CI 1.01-1.80). SCC risk was lower among non-Hispanic whites (HR 0.39, 95% CI 0.17-0.86)., Limitations: SCC risk was not examined among members without melanoma., Conclusions: SCCs arise in approximately 12% of patients with melanoma over a 5-year period and are more common among males, whites, patients older than 60 years, those with prior reportable cancers, and those with history of nonmelanoma skin cancer. Clinicians should be vigilant for SCCs among these individuals at high risk, and counsel melanoma survivors about their increased risk for SCCs., (Copyright © 2014 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Datasets from large health maintenance organizations (HMOs), particularly those with established cancer registries that report to the Surveillance, Epidemiology, and End Results program, are potentially excellent resources for studying melanoma epidemiology and outcomes. However, generalizability of the findings beyond HMO-based populations has not been well studied. We compared melanoma patient, tumor, and treatment characteristics at Kaiser Permanente Northern California and Henry Ford Healthcare Systems with those of corresponding regional, state, and national registry-reported melanoma databases. We identified all melanoma cases diagnosed at Kaiser Permanente Northern California (1996-2009) and Henry Ford Healthcare Systems (1996-2007) and ascertained patient (age, sex, race, and ethnicity), tumor (site, size, laterality, invasiveness, depth, ulceration, subtype, and stage), and treatment (surgery and radiation) variables from health system cancer registries. Registry data were obtained from Surveillance, Epidemiology, and End Results databases for the reporting period ending in November 2011. We found that melanoma cases arising in HMO settings generally have comparable patient, tumor, and treatment characteristics to regional, state, and national cases. An important difference included improved reporting of race information at HMO sites. Melanoma studies using data derived from select HMOs are potentially generalizable to local, state, and national populations, and may be better situated for studying racial-ethnic disparities.

Importance: Merkel cell carcinoma (MCC) is a rare, aggressive, neuroendocrine-derived skin cancer with high rates of recurrence and associated mortality. Few published studies have used comprehensive patient data and long-term follow-up to examine factors that predict MCC outcomes., Objective: To characterize MCC in a large defined-population cohort and analyze predictors of disease recurrence and survival., Setting, Design, and Participants: Retrospective cohort study of 218 patients with MCC from the cancer registry of Kaiser Permanente Northern California, a large integrated health care delivery system. Patients were diagnosed as having MCC and followed up from January 1, 1995, through December 31, 2009. We examined host (age, sex, race, and immunosuppression), tumor (anatomic site, size, and extent), diagnostic (results of imaging and pathologic nodal evaluation), and treatment (surgery, radiation therapy, and chemotherapy) variables for their association with MCC outcomes., Exposure: Host, tumor, diagnostic, and treatment factors., Main Outcomes and Measures: Recurrence (locoregional and distant) of MCC and patient survival (overall and MCC specific)., Results: We estimated adjusted hazard ratios (AHRs) and 95% CIs for outcomes using Cox proportional hazards regression models. After adjustment for host, tumor, diagnostic, and treatment variables, tumor extent (categorized as local, regional, and distant) remained significantly associated with all outcomes. Immunosuppression was associated with higher MCC-specific mortality (AHR, 4.9 [95% CI, 1.7-14.4]), and an unknown primary site was associated with a lower risk for distant metastasis (0.1 [0.0-0.7]) and improved survival (0.4 [0.2-0.9]). Pathological nodal evaluation was associated with a lower risk for metastasis (AHR, 0.2 [95% CI, 0.0-1.0]) and improved survival. Radiation treatment was associated with a decreased risk for locoregional recurrence (AHR, 0.3 [95% CI, 0.1-0.6]), whereas chemotherapy was not associated with any alteration in outcomes., Conclusions and Relevance: Tumor site and extent, results of pathologic nodal evaluation, and the presence of radiation treatment were associated with MCC recurrence. Immunosuppression, tumor extent, and results of pathologic nodal evaluation were associated with MCC-specific survival, whereas chemotherapy was not associated with any outcomes. Our findings may help to inform diagnostic and therapeutic management of MCCs.

Background: Melanoma incidence and mortality is a growing concern. Better recognition and management of skin cancer by primary care providers (PCPs) could help, but studies suggest they would benefit from additional education. Effective educational programs are needed., Methods: We developed and conducted a voluntary before-and-after evaluation of a 1- to 2-hour interactive, web-based course in skin cancer detection for practicing, board-certified PCPs (http://www.skinsight.com/info/for&#95;professionals/dermatology-education-resources). Voluntary participants' ability to diagnose and manage skin cancer was assessed using pretests, immediate tests, and 6-month posttests. The effect on actual practice patterns was assessed using participants' patient panels: referrals or visits to dermatology and skin biopsies during the 6 months after the course were compared with those during the same period before the course., Results: The mean age of the 54 participants was 50.5 years (standard deviation, 11.1); 54% were women and 52% were Asian. The mean score for appropriate diagnosis and management increased from 36.1% to 46.7% (odds ratio, 1.6; 95% confidence interval, 1.4-1.9), with greatest improvement in benign lesions, from 32.1% to 46.3% (odds ratio, 1.9; 95% confidence interval, 1.6-2.4). Dermatology referrals for suspicious lesions or new visits by participants' patients decreased at both sites after the course (from 630 to 607 and from 726 to 266, respectively)., Conclusions: This course improved skills in practicing PCPs. Improvement was greatest in the diagnosis and appropriate management of benign lesions and dermatology utilization decreased.

Background: Few population-based studies have reported the prevalence of psoriatic disease., Objective: We validated computerized diagnoses to estimate the prevalence of psoriasis and psoriatic arthritis., Method: We identified adults with ≥1 ICD-9 diagnosis codes of 696.0 (psoriatic arthritis) or 696.1 (psoriasis) in clinical encounter data during 1996-2009 and used chart review to confirm the diagnoses in random samples of patients. We then used the best performing case-finding algorithms to estimate the point prevalence of psoriasis and psoriatic arthritis., Results: The number of persons with a diagnosis for psoriasis (ICD-9 code 696.1) was 87 827. Chart review of a random sample of 101 cases with at least one dermatologist-rendered psoriasis code revealed a positive predictive value (PPV) of 90% (95% CI, 83-95) with sensitivity of 88% (95% CI, 80-93). Psoriatic arthritis (code 696.0) was recorded for 5187 patients, with the best performing algorithm requiring ≥2 diagnoses recorded by a rheumatologist or ≥1 diagnosis recorded by a rheumatologist together with ≥1 psoriasis diagnoses recorded by a dermatologist; the PPV was 80% (95% CI, 70-88) with sensitivity 73% (95% CI, 63-82). Among KPNC adults, the point prevalence of psoriasis, with or without psoriatic arthritis, was 939 (95% CI, 765-1142) per 100 000, and the overall prevalence of psoriatic arthritis, with or without psoriasis, was 68 (95% CI, 54-84) per 100 000., Conclusion: Within an integrated health care delivery system, the use of computerized diagnoses rendered by relevant disease specialists is a valid method for identifying individuals with psoriatic disease., (Copyright © 2013 John Wiley & Sons, Ltd.)

Objective: Few studies based in well-defined North American populations have examined the occurrence of juvenile idiopathic arthritis (JIA), and none has been based in an ethnically diverse population. We used computerized healthcare information from the Kaiser Permanente Northern California membership to validate JIA diagnoses and estimate the incidence and prevalence of the disease in this well-characterized population., Methods: We identified children aged ≤ 15 years with ≥ 1 relevant International Classification of Diseases, 9th edition, diagnosis code of 696.0, 714, or 720 in computerized clinical encounter data during 1996-2009. In a random sample, we then reviewed the medical records to confirm the diagnosis and diagnosis date and to identify the best-performing case-finding algorithms. Finally, we used the case-finding algorithms to estimate the incidence rate and point prevalence of JIA., Results: A diagnosis of JIA was confirmed in 69% of individuals with at least 1 relevant code. Forty-five percent were newly diagnosed during the study period. The age- and sex-standardized incidence rate of JIA per 100,000 person-years was 11.9 (95% CI 10.9-12.9). It was 16.4 (95% CI 14.6-18.1) in girls and 7.7 (95% CI 6.5-8.9) in boys. The peak incidence rate occurred in children aged 11-15 years. The prevalence of JIA per 100,000 persons was 44.7 (95% CI 39.1-50.2) on December 31, 2009., Conclusion: The incidence rate of JIA observed in the Kaiser Permanente population, 1996-2009, was similar to that reported in Rochester, Minnesota, USA, but 2 to 3 times higher than Canadian estimates.

Background: The epidemiological study of basal cell carcinomas (BCCs) is difficult because BCCs lack distinct disease codes and are excluded from most cancer registries., Objective: To develop and validate a large BCC registry based on electronically assigned Systematized Nomenclature of Medicine (SNOMED) codes and text-string searches of electronic pathology reports from Kaiser Permanente Northern California., Methods and Materials: Potential BCCs were identified from electronic pathology reports (n=39,026) in 2005 and were reviewed by a dermatologist who assigned case/non-case status (gold-standard). A subset of the records (n=9,428) was independently reviewed by a second dermatologist to ascertain reliability of case assignment. In addition, a subset of excluded electronic pathology reports from 2005 (n=2,700) was reviewed to determine whether inclusion criteria had missed potential BCCs. We calculated the positive predictive value (PPV) of 3 different algorithms for identifying BCCs from electronic pathology data., Results: BCC-specific SNOMED codes had the highest PPV for identifying BCCs, 0.992 (95 percent CI: 0.991-0.993). Inter-rater reliability for case assignment was high (kappa=0.92, 95 percent CI: 0.91-0.93). Standardized incidence rates were consistent with previously published rates in the United States., Conclusions: We created and validated a large BCC registry to serve as a unique resource for studying BCCs.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) have been associated with decreased risk of gastric, colorectal, and breast cancer. However, the impact of NSAIDs on the risk of melanoma has been inconsistent. The authors evaluated the association between NSAID use and cutaneous melanoma risk in the Women's Health Initiative (WHI) Observational Study (OS)., Methods: At study entry, use of aspirin (acetylsalicylic acid [ASA]) and nonaspirin NSAIDs was assessed among 59,806 postmenopausal Caucasian women ages 50 to 79 years. Cox proportional hazards models were constructed after adjusting for participant skin type, sun exposure history, and medical indications for NSAID use among other confounders., Results: During a median follow-up of 12 years, 548 incident melanomas were confirmed by medical review. Women who used ASA had a 21% lower risk of melanoma (hazard ratio, 0.79; 95% confidence interval, 0.63-0.98) relative to nonusers. Increased duration of ASA use (<1 year, 1-4 years, and ≥ 5 years) was associated with an 11% lower risk of melanoma for each categorical increase (Ptrend = .01), and women with ≥ 5 years of use had a 30% lower melanoma risk (hazard ratio, 0.70; 95% confidence interval, 0.55-0.94). In contrast, use of non-ASA NSAIDs and acetaminophen were not associated with melanoma risk., Conclusions: Postmenopausal women who used ASA had a significantly lower risk of melanoma, and longer duration of ASA use was associated with greater protection. Although this study was limited by the observational design and self-report of NSAID use, the findings suggest that ASA may have a chemopreventive effect against the development of melanoma and warrant further clinical investigation., (Copyright © 2012 American Cancer Society.)

Background The incidence of non-melanoma skin cancers (NMSCs), including basal cell (BCC) or squamous cell carcinoma (SCC), is not well documented among HIV-positive (HIV(+)) individuals. Methods We identified 6560 HIV(+) and 36 821 HIV-negative (HIV(-)) non-Hispanic white adults who were enrolled and followed up in Kaiser Permanente Northern California from 1996 to 2008. The first biopsy-proven NMSCs diagnosed during follow-up were identified from pathology records. Poisson models estimated rate ratios that compared HIV(+) (overall and stratified by recent CD4 T-cell counts and serum HIV RNA levels) with HIV(-) subjects and were adjusted for age, sex, smoking history, obesity diagnosis history, and census-based household income. Sensitivity analyses were adjusted for outpatient visits (ie, a proxy for screening). All statistical tests were two-sided. Results The NMSC incidence rate was 1426 and 766 per 100 000 person-years for HIV(+) and HIV(-) individuals, respectively, which corresponds with an adjusted rate ratio of 2.1 (95% confidence interval [CI] = 1.9 to 2.3). Similarly, the adjusted rate ratio for HIV(+) vs HIV(-) subjects was 2.6 (95% CI = 2.1 to 3.2) for SCCs, and it was 2.1 (95% CI = 1.8 to 2.3) for BCCs. There was a statistically significant trend of higher rate ratios with lower recent CD4 counts among HIV(+) subjects compared with HIV(-) subjects for SCCs (P trend < .001). Adjustment for number of outpatient visits did not affect the results. Conclusion HIV(+) subjects had a twofold higher incidence rate of NMSCs compared with HIV(-) subjects. SCCs but not BCCs were associated with immunodeficiency.

Merkel cell carcinoma (MCC) is an aggressive cutaneous malignancy linked to a contributory virus (Merkel cell polyomavirus). Multiple epidemiologic studies have established an increased incidence of MCC among persons with systemic immune suppression. Several forms of immune suppression are associated with increased MCC incidence, including hematologic malignancies, HIV/AIDS, and immunosuppressive medications for autoimmune disease or transplant. Indeed, immune-suppressed individuals represent ∼10% of MCC patients, a significant overrepresentation relative to the general population. We hypothesized that immune-suppressed patients may have a poorer MCC-specific prognosis and examined a cohort of 471 patients with a combined follow-up of 1,427 years (median 2.1 years). Immune-suppressed patients (n=41) demonstrated reduced MCC-specific survival (40% at 3 years) compared with patients with no known systemic immune suppression (n=430; 74% MCC-specific survival at 3 years). By competing risk regression analysis, immune suppression was a stage-independent predictor of worsened MCC-specific survival (hazard ratio 3.8, P<0.01). Thus, immune-suppressed individuals have both an increased chance of developing MCC and poorer MCC-specific survival. It may be appropriate to follow these higher-risk individuals more closely, and, when clinically feasible, there may be a benefit of diminishing iatrogenic systemic immune suppression.

Background: Vitamin D may have a role in many chronic conditions in addition to bone health. Nutritional surveys among Americans have reported high levels of vitamin D insufficiency, especially among Blacks and Latinos. Our study examined variation in vitamin D supplementation practices in an adult health plan population by age, gender, and race-ethnicity., Methods: Self-report data from a 2008 general health survey in a large Northern California health plan were used to characterize number and types of sources of vitamin D supplementation (multivitamin, calcium with D, singular D) among women and men aged 25-85, overall, by race-ethnicity, and for obese, diabetic, and hypertensive subgroups., Results: In this population, 40% of women and 54% of men ≤ 50, and 24% of women and 53% of men aged 51-85 get no vitamin D from dietary supplements. Higher vitamin D supplementation among women > 50 is associated with higher reported intake of calcium with D. Black and Latina women aged 25-85 and Filipinas in the ≤ 50 age group were significantly less likely than non-Hispanic Whites to get vitamin D from supplements, whereas vitamin D supplementation practices among Chinese women did not significantly differ from non-Hispanic Whites. Among men, Latinos aged 25-85 and Black and Chinese ≤ 50 were significantly less likely than non-Hispanic Whites to get vitamin D from supplements. Similar race-ethnic differences in vitamin D supplementation patterns were observed for people in the obese, diabetic, and hypertensive groups., Conclusions: Our survey results suggest that in 2008, a large percentage of women and an even larger percentage of men in a large Northern California health plan get no vitamin D from dietary supplements, and that Blacks and Latinos and obese adults, who are at higher risk of vitamin D deficiency, are also the least likely to get any vitamin D from dietary supplements.

Web-based learning in medical education is rapidly growing. However, there are few firsthand accounts on the rationale for and development of web-based learning programs. We present the experience of clinical educators who developed an interactive online skin cancer detection and management course in a time-efficient and cost-efficient manner without any prior skills in computer programming or technical construction of web-based learning programs. We review the current state of web-based learning including its general advantages and disadvantages as well as its specific utility in dermatology. We then detail our experience in developing an interactive online skin cancer curriculum for primary care clinicians. Finally, we describe the main challenges faced and lessons learned during the process. This report may serve medical educators who possess minimal computer programming and web design skills but want to employ the many strengths of web-based learning without the huge costs associated with hiring a professional development team.

Skin cancer is the most common cancer in the United States. Exposure to ultraviolet radiation is a known risk factor for skin cancer but is also the principal means by which the body obtains vitamin D. Several studies have suggested that vitamin D plays a protective role in a variety of internal malignancies. With regard to skin cancer, epidemiologic and laboratory studies suggest that vitamin D and its metabolites may have a similar protective effect. These noncalcemic actions of vitamin D have called into question whether the current recommended intake of vitamin D is too low for optimal health and cancer prevention. Part I will review the role of vitamin D in the epidermis; part II will review the role of vitamin D in keratinocyte-derived tumors to help frame the discussion on the possible role of vitamin D in the prevention of skin cancer., (Copyright © 2012 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: In screening pharmaceuticals for possible carcinogenic effects we noted an association between lip cancer risk and the photosensitizing antihypertensive drugs hydrochlorothiazide and nifedipine. In this study, we further characterized the risk of lip cancer associated with these and other commonly used antihypertensive drugs., Methods: In a comprehensive medical care program, we evaluated prescriptions dispensed and cancer occurrence from August 1, 1994, to February 29, 2008. We identified 712 patients with lip cancer (cases) and 22,904 comparison individuals (controls) matched for age, sex, and cohort year of entry in the susceptible group, non-Hispanic whites. We determined use, at least 2 years before diagnosis or control index date, of the commonly prescribed diuretics hydrochlorothiazide and hydrochlorothiazide combined with triamterene, the angiotensin-converting enzyme inhibitor lisinopril, the calcium channel blocker nifedipine, and the β-adrenergic blocker atenolol, the only nonphotosensitizer agent studied. We analyzed the use of each drug exclusively and regardless of use of the others, and focused on duration of use. Conditional logistic regression was used for analysis of matched case-control sets, with control for cigarette smoking., Results: At least a 5-year supply of a drug yielded the following odds ratios (95% CIs), respectively, compared with no use: hydrochlorothiazide, 4.22 (2.82-6.31); hydrochlorothiazide-triamterene, 2.82 (1.74-4.55); lisinopril, 1.42 (0.95-2.13); nifedipine, 2.50 (1.29-4.84); and atenolol, 1.93 (1.29-2.91). When the other drugs were excluded, the odds ratio for atenolol was reduced to 0.54 (0.07-4.08)., Conclusion: These data support an increased risk of lip cancer in non-Hispanic whites receiving treatment for hypertension with long-term use of photosensitizing drugs.

Laboratory data suggest that intake of vitamin A and carotenoids may have chemopreventive benefits against melanoma, but epidemiological studies examining the association have yielded conflicting results. We examined whether dietary and supplemental vitamin A and carotenoid intake was associated with melanoma risk among 69,635 men and women who were participants of the VITamins And Lifestyle (VITAL) cohort study in western Washington. After an average of 5.84 years of follow-up, 566 incident melanomas were identified. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for risk of melanoma associated with dietary, supplemental, and total vitamin A and carotenoid intake after adjusting for melanoma risk factors. Baseline use of individual retinol supplements was associated with a significant reduction in melanoma risk (HR: 0.60; 95% CI: 0.41-0.89). High-dose (>1,200 μg per day) supplemental retinol was also associated with reduced melanoma risk (HR: 0.74; 95% CI: 0.55-1.00), as compared with non-users. The reduction in melanoma risk was stronger in sun-exposed anatomic sites. There was no association of melanoma risk with dietary or total intake of vitamin A or carotenoids. Retinol supplementation may have a preventative role in melanoma among women.

Purpose: Use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the incidence of several cancers. A recent meta-analysis of randomized trials of aspirin reported a reduction in cancer mortality; however, few studies have investigated whether aspirin or other NSAIDs reduce overall cancer risk., Methods: 64,847 residents of western Washington State, aged 50-76, completed a baseline questionnaire in 2000-2002 and reported on their use of individual NSAIDs over the past 10 years. Behavior was categorized as non-use, low (<4 days/week or <4 years), and high (≥4 days/week and ≥4 years). Over 7 years of follow-up, 5,946 incident invasive cancer cases were identified. Multivariable proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI)., Results: Relative to non-use, high 10-year use of regular-strength NSAIDs was inversely associated with total cancer risk in men (HR 0.88, 95% CI: 0.79-0.97) and not associated with risk in women (HR 1.10, 95% CI: 0.96-1.25; p interaction <0.01). Use of regular-strength NSAIDs was strongly and inversely associated with colorectal cancer risk in men and women, but differentially associated with sex-specific risk of shared cancer sites other than colorectal cancer (men: HR 0.83, 95% CI: 0.71-0.97; women: HR 1.18, 95% CI: 0.97-1.44; p interaction < 0.01)., Conclusions: Long-term use of NSAIDs was associated with a reduced risk of total cancer among men and colorectal cancer among both sexes. Our findings do not support NSAID use for overall cancer prevention among women. Additional high-quality studies with long-term follow-up for cancer among women are needed before a public health recommendation can be made.

Cosmetic procedures have been an integral part of dermatologic surgery for over half a century, with a more recent proliferation of devices to improve skin color and texture and modify subcutaneous fat. Overall, cosmetic dermatologic procedures are extremely safe. However, detailed information about safety and effectiveness, and especially comparative effectiveness, is not available for many procedures. There are few randomized control trials of comparative effectiveness of different procedures for similar indications. Key comparative effectiveness studies are briefly reviewed, and areas of substantial deficiency in such research are highlighted., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This article reviews current recommendations, strength of evidence, and areas in need of further research in the surgical treatment of melanoma and nonmelanoma skin cancers, as well as other select cutaneous neoplasms. Cryosurgery, electrosurgery, photodynamic therapy, and surgical excision are discussed. Local anesthesia, suturing technique, postsurgical dressings, and optimization of scarring are briefly reviewed. In general, large, high-quality, randomized controlled trials on which to base recommendations are lacking., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Non-melanoma skin cancers are one of the most common human malignancies accounting for 2-3% of tumors in the US and represent a significant health burden. Epidemiology studies have implicated Tp53 mutations triggered by UV exposure, and human papilloma virus (HPV) infection to be significant causes of non-melanoma skin cancer. However, the relationship between Tp53 and cutaneous HPV infection is not well understood in skin cancers. In this study we assessed the association of HPV infection and Tp53 polymorphisms and mutations in lesional specimens with squamous cell carcinomas., Methods: We studied 55 cases of histologically confirmed cutaneous squamous cell carcinoma and 41 controls for the presence of HPV infection and Tp53 genotype (mutations and polymorphism)., Results: We found an increased number of Tp53 mutations in the squamous cell carcinoma samples compared with perilesional or control samples. There was increased frequency of homozygous Tp53-72R polymorphism in cases with squamous cell carcinomas, while the Tp53-72P allele (Tp53-72R/P and Tp53-72P/P) was more frequent in normal control samples. Carcinoma samples positive for HPV showed a decreased frequency of Tp53 mutations compared to those without HPV infection. In addition, carcinoma samples with a Tp53-72P allele showed an increased incidence of Tp53 mutations in comparison carcinomas samples homozygous for Tp53-72R., Conclusions: These studies suggest there are two separate pathways (HPV infection and Tp53 mutation) leading to cutaneous squamous cell carcinomas stratified by the Tp53 codon-72 polymorphism. The presence of a Tp53-72P allele is protective against cutaneous squamous cell carcinoma, and carcinoma specimens with Tp53-72P are more likely to have Tp53 mutations. In contrast Tp53-72R is a significant risk factor for cutaneous squamous cell carcinoma and is frequently associated with HPV infection instead of Tp53 mutations. Heterozygosity for Tp53-72R/P is protective against squamous cell carcinomas, possibly reflecting a requirement for both HPV infection and Tp53 mutations.

Mohs micrographic surgery (MMS) is a unique technique that can offer the highest cure rates and maximum tissue conservation in the management of specific primary and recurrent skin cancers. However, there are many areas of controversy that surround MMS, including appropriate indications for its use, technical quandaries, and outcomes. Recent efforts in these areas need to be assessed to identify research gaps in MMS to help fuel further work. The usefulness of MMS and its methods for delivery need more stringent, evidence-based, rigorous study., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: To identify preoperative, intraoperative, and postoperative variables that predict higher short- and long-term patient satisfaction with Mohs surgery., Design: Prospective cohort study., Setting: A university-based dermatology practice and the affiliated Veterans Affairs medical center dermatology clinic., Patients: A total of 339 consecutive patients treated with Mohs surgery in 1999 and 2000., Main Outcome Measures: Short-term satisfaction at 1 week and long-term satisfaction at 1 year. We used directed acyclic graphs to determine appropriate confounding adjustment for preoperative, intraoperative, and postoperative variables that influence satisfaction with Mohs surgery in logistic regression models., Results: Better preoperative skin-related quality of life (measured using Skindex) and more intraoperative Mohs stages were the most salient predictors of higher short- and long-term satisfaction; these odds ratios (ORs) were 2.33 (95% CI, 1.01-5.35) and 5.19 (1.66-16.29), respectively, for preoperative skin-related quality of life and 7.06 (2.02-24.67) and 5.30 (1.24-22.64), respectively, for more intraoperative Mohs stages. Patients not bothered by postoperative bleeding were more likely to be satisfied short term (OR, 2.25; 95% CI, 1.25-4.05), as were those who considered themselves involved in decision making about their treatment (3.05; 1.52-6.10). Higher long-term satisfaction with Mohs surgery was observed among patients who were married (2.36; 1.10-5.09)., Conclusions: Higher short- and long-term satisfaction with Mohs surgery is predicted by better preoperative skin-related quality of life and by more intraoperative Mohs stages. The effect of postoperative variables wanes over time, suggesting that factors influencing satisfaction can vary depending on the time frame when satisfaction is measured. Our results may help clinicians identify patients who are at higher risk of dissatisfaction following Mohs surgery.

Background: Laboratory and epidemiologic studies suggest that certain dietary supplements may alter risk of cutaneous squamous cell carcinoma (SCC)., Objective: We sought to examine the association between supplement use and SCC risk., Methods: Cases (n = 415) were defined as Kaiser Permanente Northern California members with a pathology-verified SCC in 2004 and control subjects (n = 415) were age-, sex-, and race-matched members with no history of skin cancer. Supplement use and SCC risk factors were ascertained by questionnaire. Associations of SCC with use of multivitamins; vitamins A, C, D, and E; and grape seed extract were estimated as odds ratios and 95% confidence intervals using conditional logistic regression. Models were adjusted for SCC risk factors and other supplement use., Results: Grape seed extract users had a significantly decreased risk of cutaneous SCC (adjusted odds ratio 0.26, confidence interval 0.08-0.89, P = .031). Multivitamin use was associated with a borderline significant reduction in SCC risk (adjusted odds ratio 0.71, confidence interval 0.51-1.00, P = .049). Use of vitamins A, C, D, and E was not associated with SCC risk., Limitations: The data may be prone to recall and selection bias because of the case-control design. No information was obtained on dose or duration of supplement use., Conclusions: Use of grape seed extract may be associated with a decreased risk of cutaneous SCC. The other supplements included in our study did not reveal clear associations with SCC risk., (Copyright © 2010 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.)

Background: Early detection of melanoma may provide an opportunity to positively impact melanoma mortality. Numerous skin cancer educational interventions have been developed for primary care physicians (PCPs) to improve diagnostic accuracy. Standardized training is also a prerequisite for formal testing of melanoma screening in the primary care setting., Objective: We conducted a systematic review to determine the extent of evaluated interventions designed to educate PCPs about skin cancer, including melanoma., Design: Relevant studies in the English language were identified through systemic searches performed in MEDLINE, EMBASE, BIOSIS, and Cochrane through December 2010. Supplementary information was obtained from corresponding authors of the included studies when necessary., Approach: Studies eligible for inclusion formally evaluated skin cancer education interventions and were designed primarily for PCPs. Excluded studies lacked a specified training intervention, used decision-making software, focused solely on risk factor identification, or did not directly educate or assess participants. Twenty studies met the selection criteria. Data were extracted according to intervention content and delivery format, and study outcomes., Key Results: All interventions included instructions about skin cancer diagnosis, but otherwise varied in content. Curricula utilized six distinct educational techniques, usually incorporating more than one. Intervention duration varied from 12 min to over 6 h. Eight of the 20 studies were randomized trials. Most studies (18/20, 90%) found a significant improvement in at least one of the following five outcome categories: knowledge, competence, confidence, diagnostic performance, or systems outcomes. Competence was most commonly measured; no study evaluated all categories. Variability in study design, interventions, and outcome measures prevented correlation of outcomes with intervention characteristics., Conclusions: Despite the development of many isolated educational interventions, few have been tested rigorously or evaluated under sufficient standardized conditions to allow for quantitative comparison. Improved and rigorously tested skin cancer educational interventions for PCPs with outcome measures focusing on changes in performance are needed.

Laboratory and epidemiologic studies suggest a protective effect of tea consumption on risk of cutaneous squamous cell carcinoma (SCC). We designed a case-control study to examine the association between putative protective exposures, including tea consumption, and SCC risk using a large health maintenance organization population. Cases (n=415) were defined as Kaiser Permanente Northern California (KPNC) members with a pathology-verified SCC in 2004 and controls (n=415) were age-, gender-, and race-matched members with no previous history of skin cancer. Tea consumption and SCC risk factors were ascertained by questionnaire. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression to estimate the association of SCC with regular use, as well as dose and duration of tea consumption. Risk factor adjusted models included education, smoking, hair and eye color, skin type, family history of skin cancer, and history of freckling, sunburns, sun exposure, and tanning bed use. Adjusted analyses showed no reduction in SCC risk with regular consumption of tea (OR=1.11, 95% CI: 0.81-1.54). Examining duration, dose, and combined duration and dose exposure variables did not alter findings. We found no evidence that tea consumption was associated with cutaneous SCC risk., (Copyright © 2011, Taylor & Francis Group, LLC)

Objective: The family provides an important communication nexus for information and support exchange about family cancer history, and adoption of family-wide cancer risk reduction strategies. The goals of this study were to (1) use the family systems theory to identify characteristics of this sample of families at increased risk of developing melanoma and (2) to relate familial characteristics to the frequency and style of familial risk communication., Methods: Participants were first-degree relatives (n=313) of melanoma patients, recruited into a family web-based intervention study. We used multivariable logistic regression models to analyze the association between family functioning and family communication., Results: Most participants were female (60%), with an average age of 51 years. Fifty percent of participants reported that they spoke to their relatives about melanoma risk and people were more likely to speak to their female family members. Familial adaptation, cohesion, coping, and health beliefs were strongly associated with an open style of risk communication within families. None were associated with a blocked style of risk communication. Only cohesion and adaptation were associated with the amount of risk communication that occurred within families., Conclusions: Overall, individuals who came from families that were more highly cohesive, adaptable, and shared strong beliefs about melanoma risk were more likely to communicate openly about melanoma. The fact that this association was not consistent across blocked communication and communication frequency highlights the multifaceted nature of this process. Future research should focus on the interplay between different facets of communication., (Copyright © 2010 John Wiley & Sons, Ltd.)

Objectives: To evaluate vitamin D status in patients with basal cell nevus syndrome (BCNS) who practice photoprotection because of their genetic predisposition to skin cancer and to determine risk factors for deficiency., Design: Retrospective cohort study., Setting: Academic medical centers., Patients: Forty-one ambulatory patients with BCNS who participated in a 2-year chemoprevention clinical trial. Population-based controls (n = 360) were selected and matched by age, sex, Fitzpatrick skin type, and season/geography., Main Outcome Measures: Levels of 25-hydroxyvitamin D (25[OH]D) and vitamin D deficiency (defined as a 25[OH]D level of ≤20 ng/mL)., Results: Twenty-three patients with BCNS (56%) were vitamin D deficient. Patients with BCNS had mean 25(OH)D levels below those of the general population (-3 ng/mL; P = .02) and were 3 times more likely to be vitamin D deficient (56% vs 18%; P < .001). Levels of 25(OH)D were lower in patients who were overweight (-3.0 ng/mL; P = .04) and who had blood collected in the winter compared with the summer (-7.1 ng/mL; P < .001)., Conclusion: Patients with BCNS may be at increased risk for vitamin D deficiency, depending on their adherence to photoprotection practices.

We investigated the association between serum 25-hydroxyvitamin D (25(OH)D) levels and basal cell carcinoma (BCC) risk in a nested case-control study at Kaiser Permanente Northern California (KPNC). A total of 220 case patients with BCC diagnosed after serum collection were matched to 220 control subjects. We estimated odds ratios (ORs) and 95% confidence intervals (CIs) using conditional logistic regression. Fully adjusted models included body mass index (BMI), smoking, education, sun-exposure variables, X-ray exposure, and personal history of cancer. For each measure of serum 25(OH)D (continuous, clinically relevant tertiles, quintiles), we found an increased risk of BCC in unadjusted models (OR=1.03, 95% CI 1.00-1.05, P<0.05; OR=3.98, 95% CI: 1.31-12.31, deficient vs. sufficient, test for trend P-value <0.01; OR=2.32, 95% CI: 1.20-4.50, 1st vs. 5th quintile, test for trend P-value 0.03). In fully adjusted models, the values attenuated slightly (OR=1.02, 95% CI 1.00-1.05, P<0.05; OR=3.61, 95% CI: 1.00-13.10, deficient vs. sufficient, t-trend P=0.03; OR=2.09 1st vs. 5th quintile, 95% CI: 0.95-4.58, t-trend P=0.11). Our findings suggest that higher prediagnostic serum 25(OH)D levels may be associated with increased risk of subsequent BCC. Further studies to evaluate the effect of sun exposure on BCC and serum 25(OH)D levels may be warranted.

Objective: To examine the association between nonsteroidal anti-inflammatory drug (NSAID) use and cutaneous squamous cell carcinoma (SCC)., Design: Retrospective case-control study., Setting: Kaiser Permanente Northern California (KPNC), a large population based-health maintenance organization., Patients: Random sample of 415 KPNC members diagnosed as having a pathologically verified SCC in 2004 and 415 age-, sex-, and race-matched controls with no history of skin cancer., Main Exposure Measure: Self-reported NSAID use in the 10 years prior to baseline. Use of NSAIDs was categorized based on type (any NSAIDs, aspirin, ibuprofen, and nonaspirin NSAIDs). Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression to estimate the association of SCC with regular use, dose, and duration of exposure to the different NSAID types. Information on pharmacy-dispensed NSAIDs was also examined to assess its association with SCC risk. Models were adjusted for all ascertained SCC risk factors (fully adjusted model) and only those variables associated with both SCC risk and NSAID use (parsimonious model)., Results: Fully adjusted analyses showed no statistically significant reduction in SCC risk with self-reported regular use of any NSAID (OR, 1.32; 95% CI, 0.92-1.89), aspirin (OR, 1.38; 95% CI, 0.96-1.97), ibuprofen (OR, 0.74; 95% CI, 0.46-1.19), or nonaspirin NSAIDs (OR, 0.84; 95% CI, 0.56-1.26). Analyses examining duration, dose, and variables combining duration and dose of NSAID exposure did not appreciably change results. An analysis using the parsimonious model showed similar results. The data on pharmacy-dispensed NSAIDs also showed no association with SCC risk., Conclusion: Neither self-reported nor pharmacy-dispensed NSAID exposure was associated with cutaneous SCC risk.

Recently, a population-based case-control study observed a 60% increased odds ratio (OR) for cutaneous squamous cell carcinoma (SCC) among women who had ever used oral contraceptives (OCs) compared with non users (95% confidence interval (CI) = 1.0-2.5). To further characterize the putative association between OC use and SCC risk, we conducted a nested case-control study using a large retrospective cohort of 111,521 Kaiser Permanente Northern California members. Multivariable conditional logistic regression was used to estimate ORs and CIs adjusting for known and hypothesized SCC risk factors. Pre-diagnostic OC use was associated with a statistically significant increased OR for SCC in univariate analysis (OR = 2.4, CI = 1.2-4.8), with borderline statistical significance in multivariable analysis (CI = 2.0, CI = 0.91-4.5). Given the high incidence of SCC in the general population and the prevalent use of OCs among women in the United States, there is a need for more large, carefully designed epidemiologic studies to determine whether the observed association between OC use and SCC can be replicated and to better understand the etiologic basis of an association if one exists.

Cancer registries usually exclude nonmelanoma skin cancers (NMSC), despite the large population affected. Health maintenance organization (HMO) and health system administrative databases could be used as sampling frames for ascertaining NMSC. NMSC patients diagnosed between January 1, 1988, and December 31, 2007, from such defined US populations were identified by using 3 algorithms: NMSC International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes, NMSC treatment Current Procedural Terminology (CPT) codes, or both codes. A subset of charts was reviewed to verify NMSC diagnosis, including all records from HMO-enrollee members in 2007. Positive predictive values for NMSC ascertainment were calculated. Analyses of data from 1988-2007 ascertained 11,742 NMSC patients. A random sample of 965 cases was selected for chart review, and NMSCs were validated in 47.0% of ICD-9-CM-identified patients, 73.4% of CPT-identified patients, and 94.9% identified with both codes. All charts from HMO-health plan enrollees in 2007 were reviewed (n = 1,116). Cases of NMSC were confirmed in 96.5% of ICD-9-CM-identified patients, 98.3% of CPT-identified patients, and 98.7% identified with both codes. HMO administrative data can be used to ascertain NMSC with high positive predictive values with either ICD-9-CM or CPT code, but both codes may be necessary among non-HMO patient populations.

Approximately 5% to 10% of melanoma may be hereditary in nature, and about 2% of melanoma can be specifically attributed to pathogenic germline mutations in cyclin-dependent kinase inhibitor 2A (CDKN2A). To appropriately identify the small proportion of patients who benefit most from referral to a genetics specialist for consideration of genetic testing for CDKN2A, we have reviewed available published studies of CDKN2A mutation analysis in cohorts with invasive, cutaneous melanoma and found variability in the rate of CDKN2A mutations based on geography, ethnicity, and the type of study and eligibility criteria used. Except in regions of high melanoma incidence, such as Australia, we found higher rates of CDKN2A positivity in individuals with 3 or more primary invasive melanomas and/or families with at least one invasive melanoma and two or more other diagnoses of invasive melanoma and/or pancreatic cancer among first- or second-degree relatives on the same side of the family. The work summarized in this review should help identify individuals who are appropriate candidates for referral for genetic consultation and possible testing.

Objective: To examine whether antioxidant supplement use is associated with melanoma risk in light of recently published data from the Supplementation in Vitamins and Mineral Antioxidants (SUVIMAX) study, which reported a 4-fold higher melanoma risk in women randomized to receive a supplement with nutritionally appropriate doses of antioxidants., Design: Population-based prospective study (Vitamins and Lifestyle [VITAL] cohort)., Setting: Western Washington State., Participants: A total of 69 671 men and women who self-reported (1) intake of multivitamins and supplemental antioxidants, including selenium and beta carotene, during the past 10 years and (2) melanoma risk factors on a baseline questionnaire. Main Outcome Measure Incident melanoma identified through linkage to the Surveillance, Epidemiology, and End Results (SEER) cancer registry., Results: Cox proportional hazards regression models were used to estimate multivariable relative risks (RRs) and 95% confidence intervals (CIs) for multivitamin, supplemental selenium, and supplemental beta carotene use. After adjusting for melanoma risk factors, we did not detect a significant association between multivitamin use and melanoma risk in women (RR, 1.14; 95% CI, 0.78-1.66) or in men (RR, 1.09; 95% CI, 0.83-1.43). Moreover, we did not observe increased melanoma risk with the use of supplemental beta carotene (RR, 0.87; 95% CI, 0.48-1.56) or selenium (RR, 0.98; 95% CI, 0.69-1.41) at doses comparable with those of the SUVIMAX study. Conclusion Antioxidants taken in nutritional doses do not seem to increase melanoma risk.

Background: Patient satisfaction is an important aspect of patient-centered care but has not been systematically studied after treatment of nonmelanoma skin cancer (NMSC), the most prevalent cancer., Objective: To compare patient satisfaction after treatment for NMSC and to determine factors associated with better satisfaction., Methods: We prospectively measured patient, tumor, and care characteristics in 834 consecutive patients at two centers before and after destruction, excision, and Mohs surgery. We evaluated factors associated with short-term and long-term satisfaction., Results: In all treatment groups, patients were more satisfied with the interpersonal manners of the staff, communication, and financial aspects of their care than with the technical quality, time with the clinician, and accessibility of their care (p<.05). Short-term satisfaction did not differ across treatment groups. In multivariable regression models adjusting for patient, tumor, and care characteristics, higher long-term satisfaction was independently associated with younger age, better pretreatment mental health and skin-related quality of life, and treatment with Mohs surgery (p<.05)., Conclusions: Long-term patient satisfaction after treatment of NMSC is related to pretreatment patient characteristics (mental health, skin-related quality of life) and treatment type (Mohs) but not tumor characteristics. These results can guide informed decision-making for treatment of NMSC.

Data suggest that vitamin D intake may have chemopreventive efficacy against melanoma, but there have been no published epidemiologic studies examining the association between vitamin D intake and melanoma risk in a large prospective cohort. We examined whether dietary and supplemental vitamin D intake was associated with melanoma risk among 68,611 men and women who were participants of the Vitamins and Lifestyle cohort study. Participants reported dietary vitamin D intake over the past year and 10-year use of multivitamin and individual vitamin D supplements on a baseline questionnaire. After follow-up through 2006, 455 incident melanomas were identified through linkage to the Surveillance, Epidemiology, and End Results cancer registry. Cox proportional hazards regression models were used to estimate relative risks (RRs) and 95% confidence intervals (CIs) for vitamin D intake after adjustment for melanoma risk factors. Compared with the lowest quartile, we did not detect a risk reduction of melanoma in the highest quartiles of dietary vitamin D intake (RR=1.31, CI=0.94-1.82), 10-year average supplemental vitamin D intake (RR=1.13, CI=0.89-1.43), or combined dietary and supplemental intake (1.05, CI=0.79-1.40). In this large prospective cohort, we did not find an association between vitamin D intake and melanoma risk.

Objective: We examined the association between statin use and basal cell carcinoma (BCC) risk., Methods: We identified all members of a large integrated health care delivery system with a diagnosis of a histologically proven BCC in 1997. Subsequent BCCs were identified through 2006 from health plan electronic pathology records. Longitudinal exposure to statins and other lipid-lowering agents was determined from automated pharmacy records. We used extended Cox regression to examine the independent association between receipt of statin therapy (ever vs never, cumulative duration) and risk of subsequent BCC. To minimize confounding by indication, we conducted sensitivity analyses in the subset of individuals considered eligible for lipid-lowering therapy based on national guidelines., Results: Among 12,123 members given a diagnosis of BCC who had no prior statin exposure, 6381 developed a subsequent BCC during follow-up. Neither "ever use of statins" (adjusted hazard ratio 1.02, 95% confidence interval: 0.92-1.12) or cumulative duration of statin (adjusted hazard ratio 1.02/year, 95% confidence interval: 0.99-1.11) was associated with subsequent BCC after adjustment for age, sex, and health care use. Risk estimates did not change appreciably when the analysis was limited to the subset of individuals who met eligibility criteria for initiating statin therapy. There was also no significant association between use of non-statin antilipemics and subsequent BCC (adjusted hazard ratio 1.10, 95% confidence interval: 0.76-1.58)., Limitations: No information was available for BCC risk factors, such as sun sensitivity and sun exposure., Conclusions: Among a large cohort of individuals with BCC, statin therapy was not significantly associated with risk of subsequent BCC.

Results of laboratory studies indicate that nonsteroidal anti-inflammatory drugs (NSAIDs) may have chemopreventive activity and therapeutic efficacy against melanoma. However, few published epidemiological studies have examined the association between NSAID use and melanoma risk. We examined whether NSAID use was associated with melanoma risk among 63 809 men and women in the Vitamins and Lifestyle (VITAL) cohort study. Participants self-reported NSAID use (low-dose aspirin, regular or extra-strength aspirin, and nonaspirin NSAIDs) during the previous 10 years and data related to their melanoma risk factors on a baseline questionnaire. After linkage of the VITAL database to the NCI Surveillance, Epidemiology, and End Results cancer registry, 349 patients with incident melanoma were identified through December 31, 2005. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) of melanoma by NSAID use as categorized by overall use, duration of use, and dose (expressed as average number of days of use during the past 10 years). All statistical tests were two-sided. After adjusting for melanoma risk factors and indications for NSAID use, no association between NSAID use and melanoma risk was found. When use of at least 4 d/wk was compared with nonuse, no melanoma risk reduction was detected for any NSAID dose (HR = 1.12, 95% CI = 0.84 to 1.48), for any NSAID excluding low-dose aspirin (HR = 1.03, 95% CI = 0.74 to 1.43), for regular- or extra-strength aspirin (HR = 1.10, 95% CI = 0.76 to 1.58), or for nonaspirin NSAIDs (HR = 1.22, 95% CI = 0.75 to 1.99). Moreover, NSAID use was not associated with tumor invasion (P(interaction) = .38), tumor thickness (P(trend) = .98), or risk of metastasis (HR = 1.09, 95% CI = 0.32 to 3.62). NSAIDs do not appear to be good candidates for the chemoprevention of melanoma.

The presence of certain types of human papillomavirus (HPV) is a known risk factor for the development of anogenital squamous cell carcinomas (SCCs). A similar association has been hypothesized for cutaneous SCCs, although, to our knowledge, no studies to date have combined sensitive HPV DNA detection techniques with epidemiologic data controlling for known risk factors to explore the association. We designed a case-control study examining HPV prevalence using highly sensitive PCR-detection assays in tissue samples from 85 immunocompetent patients with histologically confirmed SCCs and 95 age-matched individuals without a prior history of skin cancer. A standardized interview was administered to all study subjects to collect information pertaining to potential confounding variables. The overall detection rate of HPV DNA was high in case lesions (54%) and perilesions (50%) and in both sun-exposed normal tissue (59%) and non-sun-exposed normal tissue (49%) from controls. In comparing case tissue to control tissue, there was no differential detection of HPV DNA across various HPV species. However, HPV DNA from beta-papillomavirus species 2 was more likely to be identified in tumors than in adjacent healthy tissue among cases (paired analysis, odds ratio=4.0, confidence interval=1.3-12.0). The high prevalence of HPV DNA detected among controls suggests that HPV DNA is widely distributed among the general population. However, the differential detection of HPV beta-papillomavirus species in tumors among cases suggests that certain HPV types may be involved in the progression of cutaneous SCCs.

Background: Cutaneous angiosarcoma is a rare, life-threatening tumor that is often initially misdiagnosed. This delay in diagnosis can affect tumor growth, metastatic potential, and prognosis., Observations: We describe the "head-tilt maneuver," which highlights the vascular nature of these lesions and can be of potential benefit in early recognition and better appreciation of the clinical extent of this tumor., Conclusion: Early recognition and aggressive management of these tumors can afford the best opportunity for cure.

Compartment syndrome of the extremity may occur after severe trauma secondary to fractures, vascular ischemia, crush, or electrical injury. Treatment consists of expedient fasciotomy to avoid permanent injury to muscles or nerves. Management of the wounds postoperatively has consisted traditionally of primary closure, healing by secondary intention, or split-thickness skin grafting to cover defects. The fasciotomy wound may remain substantial secondary to soft-tissue swelling and edema. The authors present an alternative protocol for fasciotomy wound management, consisting of gradual closure with progressive tension using vessel loops. The vessel loops are placed intraoperatively during the compartment release and are attached to the wound margins using standard skin staples. The loops are tightened progressively postoperatively during routine dressing changes, resulting in closure of the wound within 2 weeks. The advantages over split-thickness grafting include avoidance of donor morbidity and better cosmesis. Sporadic case reports using similar techniques have been published in the orthopedic literature with comparable results. The current series includes 37 patients, ages 9 to 48 years, who were treated for open fasciotomy. There were 11 upper extremity and 26 lower extremity wounds treated, all of which were closed within 3 weeks.

Thymidine phosphorylase/platelet-derived endothelial cell growth factor (TPase/PD-ECGF) is a catabolic enzyme that has been shown to be chemotactic for endothelial cells in vitro and angiogenic in vivo. TPase/PD-ECGF expression is increased in a variety of tumors. In the skin, TPase is active in normal keratinocytes in vitro and in vivo. Our objective was to study the expression and localization of TPase/PD-ECGF by immunohistochemical analysis in normal skin and cutaneous tumors and to correlate this information with enzymatic activity of TPase. TPase/PD-ECGF expression was observed in keratinocytes with intense staining of the infundibulum of hair follicles but no staining of hair bulbs. Expression localized primarily to the nucleus of keratinocytes in the basal layer but was more intense and cytoplasrmic in suprabasal keratinocytes. Increased expression of TPase/PD-ECGF in differentiated cells was confirmed by in vitro studies of TPase activity. In cutaneous tumors, there was positive staining for TPase/ PD-ECGF in squamous cell carcinomas (10/10), eccrine poromas (3/4), eccrine syringomas (4/4), trichoepitheliomas (1/3), and tumors of the follicular infundibulum (2/3) and melanomas (5/8). There was no staining of any intradermal nevi (0/2), basal cell carcinomas (0/10) or Merkel cell carcinoma (0/1). We conclude TPase/PD-ECGF is found throughout the epidermis and its expression increases with differentiation of keratinocytes. In cutaneous tumors, expression of TPase/PD-ECGF may be linked to the cell of origin of the tumor as well as the tumor's degree of differentiation.