Jeremy S. Bordeaux

Topical Imiquimod or Fluorouracil Therapy for Basal and Squamous Cell Carcinoma: A Systematic Review

OBJECTIVES To conduct a systematic review to determine clearance rates and adverse effects of topical imiquimod or fluorouracil therapy in the treatment of nonmelanoma skin cancers such as basal (BCC) and squamous cell carcinoma (SCC), and to develop recommendations for the use of topical imiquimod or fluorouracil to treat BCC and SCC. DATA SOURCES MEDLINE, CANCERLIT, and Cochrane databases. STUDY SELECTION Prospective, retrospective, and case studies in English containing a minimum of 4 subjects and a 6-month follow-up or posttreatment histologic evaluation. DATA EXTRACTION We calculated the rate of clearance and adverse effects for BCC subtypes and invasive and in situ SCC treated with topical imiquimod or fluorouracil. DATA SYNTHESIS Clearance rates varied by drug regimen, and most of the studies lacked long-term follow-up. Imiquimod use produced the following clearance rates: 43% to 100% for superficial BCC, 42% to 100% for nodular BCC, 56% to 63% for infiltrative BCC, 73% to 88% for SCC in situ, and 71% for invasive SCC. Fluorouracil use produced the following clearance rates: 90% for superficial BCC and 27% to 85% for SCC in situ. Up to 100% and 97% of patients applying imiquimod and fluorouracil, respectively, experienced at least 1 adverse event. Adverse event intensity ranged from mild to severe; erythema, pruritus, and pain were common. CONCLUSIONS Evidence supports the use of topical imiquimod as monotherapy for superficial BCC and topical fluorouracil as monotherapy for superficial BCC and SCC in situ. Based on the available evidence, the strength of any recommendations for the use of these 2 agents in the primary treatment of these tumors is weak. We recommend that their use be limited to patients with small tumors in low-risk locations who will not or cannot undergo treatment with better-established therapies for which long-term clearance rates have been determined. Long-term clinical follow-up is essential for patients treated with topical imiquimod or fluorouracil. Limitations of therapy include high rates of adverse effects, lower clearance rates than other treatment modalities, dependence on patient adherence to treatment, and higher costs than other therapies.

Melanoma in solid organ transplant recipients.

This manuscript outlines estimated risk and clinical course of pretransplant MM, donor‐transmitted MM and de novo MM posttransplantation and includes an analysis of risk factors for metastasis, data from clinical studies and current and proposed management. MM in situ and thin melanoma (<1 mm) in the transplant population has similar recurrence and survival estimates to those in the general population. A minimum wait time of 2 years prior to transplantation is suggested for MM with a Breslow depth <1 mm and no clinical evidence of metastasis. More advanced MM may adopt a more aggressive course in transplant recipients. Sentinel lymph node biopsy may be of additional prognostic benefit. Revision of immunosuppression in the management of de novo melanoma in collaboration with the transplant team should be considered. Larger studies utilizing uniform staging criteria or at minimum Breslow depth, are required to assess true risk and outcome of MM in the immunosuppressed transplant population. Emphasis remains on patient education and regular screening to provide early detection of MM.

The role of massage in scar management: a literature review.

Background Many surgeons recommend postoperative scar massage to improve aesthetic outcome, although scar massage regimens vary greatly. Objective To review the regimens and efficacy of scar massage. Methods PubMed was searched using the following key words: “massage” in combination with “scar,” or “linear,” “hypertrophic,” “keloid,” “diasta*,” “atrophic.” Information on study type, scar type, number of patients, scar location, time to onset of massage therapy, treatment protocol, treatment duration, outcomes measured, and response to treatment was tabulated. Results Ten publications including 144 patients who received scar massage were examined in this review. Time to treatment onset ranged from after suture removal to longer than 2 years. Treatment protocols ranged from 10 minutes twice daily to 30 minutes twice weekly. Treatment duration varied from one treatment to 6 months. Overall, 65 patients (45.7%) experienced clinical improvement based on Patient Observer Scar Assessment Scale score, Vancouver Scar Scale score, range of motion, pruritus, pain, mood, depression, or anxiety. Of 30 surgical scars treated with massage, 27 (90%) had improved appearance or Patient Observer Scar Assessment Scale score. Conclusions The evidence for the use of scar massage is weak, regimens used are varied, and outcomes measured are neither standardized nor reliably objective, although its efficacy appears to be greater in postsurgical scars than traumatic or postburn scars. Although scar massage is anecdotally effective, there is scarce scientific data in the literature to support it.

Staging for Cutaneous Squamous Cell Carcinoma as a Predictor of Sentinel Lymph Node Biopsy Results: Meta-analysis of American Joint Committee on Cancer Criteria and a Proposed Alternative System

IMPORTANCE The appropriate clinical setting for the application of sentinel lymph node biopsy (SLNB) in the management of cutaneous squamous cell carcinoma (cSCC) is not well characterized. Numerous case reports and case series examine SLNB findings in patients who were considered to have high-risk cSCC, but no randomized clinical trials have been performed. OBJECTIVE To analyze which stages in the American Joint Committee on Cancer (AJCC) criteria and a recently proposed alternative staging system are most closely associated with positive SLNB findings in nonanogenital cSCC. DESIGN, SETTING, AND PARTICIPANTS Medical literature review and case data extraction from private and institutional practices to identify patients with nonanogenital cSCC who underwent SLNB. Patients were eligible if sufficient tumor characteristics were available to classify tumors according to AJCC staging criteria and a proposed alternative staging system. One hundred thirty patients had sufficient data for AJCC staging, whereas 117 had sufficient data for the alternative system. EXPOSURE Nonanogenital cSCC and SLNB. MAIN OUTCOMES AND MEASURES Positive SLNB findings by cSCC stage, quantified as the number and percentage of positive nodes. RESULTS A positive SLN was identified in 12.3% of all patients. All cSCCs with positive SLNs were greater than 2 cm in diameter. The AJCC criteria identifed positive SLNB findings in 0 of 9 T1 lesions (0%), 13 of 116 T2 lesions (11.2%), and 3 of 5 T4 lesions (60.0%). No T3 lesions were identified. The alternative staging system identified positive SNLB findings in 0 of 9 T1 lesions (0%), 6 of 85 T2a lesions (7.1%), 5 of 17 T2b lesions (29.4%), and 3 of 6 T3 lesions (50.0%). Rates of positive SLNB findings in patients with T2b lesions were statistically higher than those with T2a lesions (P = .02, Fisher exact test) in the alternative staging system. CONCLUSIONS AND RELEVANCE Our findings suggest that most cSCCs associated with positive SLNB findings occur in T2 lesions (in both staging systems) that are greater than 2 cm in diameter. The alternative staging system appears to more precisely delineate high-risk lesions in the T2b category that may warrant consideration of SLNB. Future prospective studies are necessary to validate the relationship between tumor stage and positive SLNB findings and to identify the optimal staging system.

Surgical management of congenital dermatofibrosarcoma protuberans

Congenital dermatofibrosarcoma protuberans (DFSP) is a rare tumor with varying clinical presentations that is commonly misdiagnosed. Treatment of congenital DFSP is complicated by delays in diagnosis and its propensity for subclinical spread. Of 61 reported cases, 11 (18%) were treated with Mohs micrographic surgery (MMS) and 46 (75%) were treated with wide local excision (WLE). One case was treated with imatinib, and the remaining 3 did not differentiate between receiving MMS or WLE. In the cases of congenital DFSP treated with MMS the clearance rate was 100% with an average follow-up of 4.3 years. The clearance rate seen with WLE was 89% with an average follow-up period of 1.9 years. The average margins taken during MMS (1.7 cm) were smaller than those taken with WLE (2.8 cm). Fifty percent of cases with available follow-up undergoing WLE required multiple surgeries. Based on superior cure rates with long-term follow-up, smaller surgical margins, and fewer surgical sessions, MMS should be considered as first-line treatment for congenital DFSP.

Non-melanoma skin cancers: Photodynamic therapy, cryotherapy, 5-fluorouracil, imiquimod, diclofenac, or what? Facts and controversies

Surgical modalities-excision, Mohs micrographic surgery, and electrodesiccation with curettage-are the preferred treatments for nonmelanoma skin cancer (NMSC). When used within guidelines, they have cure rates greater than 90%. Despite this, many other treatments have been studied and utilized for NMSC. We present a comprehensive review of the literature on these topical treatments. Photodynamic therapy (PDT) is administered under numerous and significantly varied regimens, and there are a wide range of cure rates reported. Even with aggressive regimens, PDT is not as effective as surgery is, and it is not a first-line therapy for NMSC. The cryotherapy regimen aggressive enough to adequately treat NMSC carries adverse effects and cosmetic outcomes poor enough to negate its usefulness. Topical 5-fluorouracil and imiquimod are efficacious and safe for the treatment of superficial basal cell carcinoma (BCC) but not other BCC subtypes or squamous cell carcinoma. They are self-administered twice daily for several weeks; therefore, patient and tumor selection are vital to ensuring adherence. There are currently insufficient data to support the use of topical diclofenac and ingenol mebutate for NMSC.

Early detection of melanoma: reviewing the ABCDEs.

Over the course of their nearly 30-year history, the ABCD(E) criteria have been used globally in medical education and in the lay press to provide simple parameters for assessment of pigmented lesions that need to be further evaluated by a dermatologist. In this article, the efficacy and limitations of the ABCDE criteria as both a clinical tool and a public message will be reviewed.

Association of Increased Dermatologist Density With Lower Melanoma Mortality

OBJECTIVE To determine whether there is an association between dermatologist density and melanoma mortality. DESIGN A regression model was developed to test the association between melanoma mortality and dermatologist density, controlling for county demographics, health care infrastructure, and socioeconomic factors. Data were collected from the Area Resource File, US Centers for Disease Control and Prevention, and National Cancer Institutes Surveillance, Epidemiology, and End Results program and National Program for Cancer Registries. SETTING US counties. PATIENTS Melanoma mortality and incidence data were reported as age-adjusted mean rates per 100 000 people from January 2002, through December 2006. MAIN OUTCOME MEASURE The primary outcome measure was melanoma mortality rate per 100 000 people at the county level. RESULTS Geographic variation exists in the distribution of dermatologists across the United States. Multivariate analysis demonstrated that the presence of 0.001 to 1 dermatologist per 100 000 people was associated with a 35.0% reduction in the melanoma mortality rate (95% CI, 13.4%-56.6%) when compared with counties with no dermatologist. The presence of 1.001 to 2 dermatologists per 100 000 people was associated with a 53.0% reduction in the melanoma mortality rate (95% CI, 30.6%-75.4%). Having more than 2 dermatologists per 100 000 people did not further lower melanoma mortality rates. CONCLUSION Within a given county, a greater dermatologist density is associated with lower melanoma mortality rates compared with counties that lacked a dermatologist.

Patterns of cancer screening in primary care from 2005 to 2010.

Cancer screening recommendations vary widely, especially for breast, prostate, and skin cancer screening. Guidelines are provided by the American Cancer Society, the US Preventive Services Task Force, and various professional organizations. The recommendations often differ with regard to age and frequency of screening. The objective of this study was to determine actual rates of screening in the primary care setting.

Risk and Survival of Cutaneous Melanoma Diagnosed Subsequent to a Previous Cancer

OBJECTIVE To understand the risk of cutaneous melanoma (CM) following a previous cancer. DESIGN Using the Surveillance, Epidemiology, and End Results database (1988-2007), we compared a cohort of patients diagnosed as having CM as a first cancer with a cohort of patients diagnosed as having CM following a previous cancer. PARTICIPANTS We included 70,819 patients with CM as a first primary cancer and 6353 patients with CM following a previous cancer. MAIN OUTCOME MEASURES We calculated the relative risk (RR) for development of primary CM following a previous cancer and used Cox modeling to examine survival characteristics of the 2 cohorts. RESULTS Patients younger than 45 years at first cancer diagnosis had significantly higher risk of CM following cutaneous melanoma (RR, 11.89; 95% CI, 10.83-13.03), other nonepithelial skin cancer (RR, 2.81; 95% CI, 1.13-5.79), Kaposi sarcoma (RR, 3.26; 95% CI 1.41-6.42), female breast cancer (RR, 1.38; (1.11-1.70), and lymphoma (RR, 1.79; (95% CI, 1.30-2.41). Patients 45 years or older at first cancer diagnosis had significantly higher risk of CM following cutaneous melanoma (RR, 8.36; 95% CI, 7.93-8.81), other nonepithelial skin cancer (RR, 2.00; 95% CI 1.35-2.86), ocular melanoma (RR, 5.34; 95% CI 3.42-7.94), female breast cancer (RR, 1.12; 95% CI, 1.03-1.21), prostate cancer (RR, 1.08; 95% CI, 1.03-1.13), thyroid cancer (RR, 1.40; 95% CI, 1.06-1.82), lymphoma (RR, 1.34; 95% CI, 1.16-1.55), and leukemia (RR, 1.79; 95% CI, 1.49-2.13). Characteristics associated with better survival in both cohorts included female sex, age younger than 45 years at melanoma diagnosis, being married, being white vs black, decreasing Breslow depth, lack of tumor ulceration, no nodal involvement, and absence of metastases. CONCLUSION Given that cutaneous melanoma is the most common second primary cancer in patients with a first CM (a risk that remains elevated for over 15 years), our results suggest the need for continued skin surveillance in melanoma survivors.