Analgesic and nonsteroidal anti-inflammatory use in relation to nonmelanoma skin cancer: a population-based case-control study.

BACKGROUND: Aspirin and other nonsteroidal anti-inflammatory drugs (NSAIDs) are potentially chemopreventive. OBJECTIVE: We examined the relation between NSAID use and nonmelanoma skin cancer in a population-based case-control study. METHODS: NSAID and analgesic use was analyzed in 1484 participants: 535 with squamous cell carcinoma (SCC), 487 with basal cell carcinoma (BCC), and 462 control subjects. RESULTS: Use of NSAIDs, particularly aspirin, was associated with a reduced odds ratio (OR) of SCC, especially tumors positive for p53 (OR 0.29; 95% confidence interval 0.11-0.79) or with PTCH loss of heterozygosity (OR 0.35; 95% confidence interval 0.13-0.96). Although not considered a NSAID, decreased ORs of both basal cell carcinoma and SCC were observed in relation to use of paracetamol (acetaminophen). Risk of BCC was unrelated to NSAID use. LIMITATIONS: Self-reported drug use was a limitation. CONCLUSIONS: This study supports the hypothesis that NSAIDs, aspirin in particular, may reduce risk of SCC and may affect specific molecular subtypes of SCC.

Spitz nevi arising in speckled lentiginous nevus: clinical, histologic, and molecular evaluation of two cases.

Spitz nevi are small dome-shaped nodules that sometimes arise in areas of preexisting hyperpigmentation, such as a speckled lentiginous nevus (nevus spilus), where they present a diagnostic dilemma. We report clinical, histopathological, and molecular findings of two cases of multiple Spitz nevi arising in a speckled lentiginous nevus. We used immunohistochemistry to assess expression of Ki-67, epidermal growth factor receptor, vascular endothelial growth factor, and RelA in two cases of Spitz nevi arising in a speckled lentiginous nevus. We observed rare staining for the proliferative marker Ki-67, but positive staining for the growth and antiapoptotic factors epidermal growth factor receptor, vascular endothelial growth factor, and RelA. Characterization of the molecular phenotype of Spitz nevi arising in speckled lentiginous nevi may provide a useful adjunct to long-term monitoring in this rare but difficult clinical presentation.

Oral lichen planus: a case series with emphasis on therapy.

BACKGROUND: Oral lichen planus (OLP) is a chronic inflammatory disorder that can cause local irritation and discomfort with attendant poor dentition and nutrition. Although a range of therapeutic options is available, data on the long-term efficacy of treatments for this chronic disease are limited. To identify agents that might be effective in OLP treatment over a longer term, and to explore their sequential use in treatment-refractory patients, we studied patients who received multiple OLP therapies and who were followed up for an average of more than 2 years. OBSERVATIONS: We performed a retrospective medical record review of 50 patients with histologically confirmed OLP. Patients were treated according to a therapeutic ladder of sequential treatments, beginning with topical corticosteroids and progressing through topical immunomodulators, systemic retinoids, methotrexate, and thalidomide. The best responses were observed in previously untreated patients. Most patients eventually achieved a substantial response with limited toxic effects. CONCLUSIONS: Our results identify low-dose methotrexate as an agent with substantial activity in OLP. We also demonstrate that a laddered therapeutic approach to patients with this disease can achieve substantial lesion regression even in heavily pretreated and treatment-refractory patients.

Interleukin-12, interleukin-23, and psoriasis: current prospects.

The clinical phenotype of psoriasis results from infiltration of T cells in the skin and elaboration of inflammatory cytokines. Interleukin (IL)-12 and, more recently, IL-23 have been implicated in the pathogenesis of psoriatic lesions. New therapies, including a monoclonal antibody against a subunit shared by IL-12 and IL-23, have been developed to treat psoriasis. Our purpose was to review the literature on IL-12 and IL-23 as a basis for understanding the use of anti-IL-12/IL-23 therapy for psoriasis. A review of English-language articles was performed using PubMed to identify articles pertaining to IL-12, IL-23, and psoriasis. IL-12 and IL-23 share a common subunit (p40) and have a distinct subunit (p35 and p19, respectively). Transgenic mice that overexpress IL-12 p40 develop inflammatory skin lesions. Both IL-12 knockout mice, which are deficient in IL-12, and human beings with a genetic IL-12 deficiency show increased susceptibility to intracellular pathogens and defective delayed-type hypersensitivity responses. These genetic deficiency states suggest the potential for adverse side effects from clinical administration of anti IL-12 p40 therapy. IL-12 p40 antibody was well tolerated in a phase I clinical trial with few adverse events and substantial improvements in psoriasis in most individuals. There was dose-dependent efficacy and substantial improvement in a larger cohort of patients in a phase II clinical trial. Larger and longer trials of anti IL-12/IL-23 therapies are needed to assess their clinical use and potential for infection and other adverse events.

Exercise and prostate cancer.

Prostate cancer is a leading cause of cancer morbidity and mortality in men. In addition to improved treatments, strategies to reduce disease risk are urgently required. This review summarises the literature that examines the association between exercise and prostate cancer risk. Between 1989 and 2001, 13 cohort studies were conducted in the US and internationally. Of these, nine showed an association between exercise and decreased prostate cancer risk. Five of 11 case-control studies conducted between 1988 and 2002 reported an association between decreased risk of prostate cancer and high activity levels. Considering all studies performed between 1976 and 2002, 16 out of 27 studies reported reduced risk in men who were most active; in nine out of 16 studies the reduction in risk was statistically significant. Average risk reduction ranged from 10-30%. In aggregate, this evidence suggests a probable link between increased physical exercise and decreased prostate cancer risk. The ability of exercise to modulate hormone levels, prevent obesity, enhance immune function and reduce oxidative stress have all been postulated as mechanisms that may underlie the protective effect of exercise. Exercise may also be of benefit in men undergoing treatment for prostate cancer. Overall, study design and control of potential confounding factors varied greatly among studies, possibly contributing to the variation in results. Epidemiological studies that are better controlled, larger in scale and more carefully designed may help to more fully clarify the relationship between exercise and prostate cancer. In addition, intervention trials that test whether exercise programmes can reduce prostate cancer risk are currently underway to rigorously test the ability of exercise to reduce prostate cancer incidence.

Managing hot flashes in men being treated for prostate cancer.

Prostate cancer is the most common malignancy in men. Treatment with hormonal ablation is often accompanied by disabling hot flashes. This article reviews the pathophysiology of hot flashes and treatment options for this common side effect of treatment.