Long-term outcomes of Mohs micrographic surgery for invasive melanoma of the trunk and proximal portion of the extremities.

BACKGROUND: Microscopic evaluation of the entire surgical margin during excision of cutaneous malignancies results in the highest rates of complete excision and lowest rates of true local scar recurrence. Few studies demonstrate the outcomes of Mohs micrographic surgery specifically for invasive melanoma of the trunk and proximal portion of the extremities. OBJECTIVE: To evaluate the long-term efficacy of Mohs micrographic surgery for invasive melanoma of the trunk and proximal portion of the extremities, including true local scar recurrence rate, distant recurrence-free survival, and disease-specific survival. METHODS: Prospectively collected study of 1416 cases of invasive melanoma of the trunk and proximal portion of the extremities was performed to evaluate long-term outcomes. RESULTS: True local scar recurrences occurred in our cohort at a rate of 0.14% (2/1416), after a mean follow-up period of 75 months and were not associated with tumor depth. The rate of satellite/in-transit recurrences and the disease-specific survival stratified by tumor thickness were superior to historical control values. LIMITATIONS: We used a nonrandomized, single institution, retrospective design. CONCLUSIONS: Mohs micrographic surgery of primary cutaneous invasive melanoma on the trunk and proximal portion of the extremities resulted in local control of 99.86% of tumors and an overall disease-specific death rate superior to that of wide local excision.

Lipophagic Panniculitis of Childhood: A Case Report and Comprehensive Review of the Literature.

Lipophagic panniculitis of childhood is a rare condition notable clinically for an inflammatory panniculitis followed by the development of permanent lipoatrophy. In this regard, the term lipoatrophic panniculitis has been used synonymously with lipophagic panniculitis. Additional designations include lipophagic lipoatrophic panniculitis and annular lipoatrophic panniculitis of the ankles. Although lipophagic panniculitis has been associated with a number of autoimmune phenomena, a paucity of reports and limited pathological analyses to date renders this disease an elusive one whose pathogenesis is not yet established. We describe the clinical, histopathologic, and immunohistochemical findings in a case of lipophagic panniculitis of childhood in a 7-year-old boy and present it in the context of a comprehensive review of the literature. Furthermore, we offer a hypothesis regarding the pathogenetic basis of lipophagic panniculitis of childhood, suggesting cellular immunity targeting the adipocyte at the crux of its pathogenesis.

Sunscreens: obtaining adequate photoprotection.

Adequate photoprotection plays a paramount role in reducing the burden of both photoaging and photocarcinogenesis. The scope of photoprotective strategies employed by the public, from most to least effective, includes: sun avoidance, seeking shade, the use of protective clothing, and the application of sunscreen. Among these options, sunscreen use remains the strategy most frequently employed by the public--a reversal of the preferred order of photoprotection. Given this trend, it is clear why sunscreens invariably take center stage in any discussion regarding obtaining adequate photoprotection.

Current sunscreen controversies: a critical review.

BACKGROUND/PURPOSE: Sunscreens are believed to be a valuable tool in providing photoprotection against the detrimental effects of UV radiation, a known carcinogen. However, a number of controversies have developed regarding their safety and efficacy. This review summarizes the relevant studies surrounding these controversies. METHODS: Evidence of the prevention of skin cancer, an oft-cited reason for sunscreen use, was examined as it pertains to squamous cell carcinoma, basal cell carcinoma and melanoma. We also reviewed studies examining the effects of sunscreen on the synthesis of vitamin D, an essential nutrient whose role in health and disease continues to grow. Lastly, we analyzed studies surrounding the safety and toxicity of oxybenzone, retinyl palmitate and nanoparticles of zinc oxide (ZnO) and titanium dioxide (TiO2 ). RESULTS: The overwhelming majority of available data is drawn from studies conducted using antiquated sunscreen formulations. Nonetheless, our research revealed that topical use of sunscreen protects against squamous cell carcinoma, does not cause vitamin D deficiency/insufficiency in practice and has not been demonstrated to adversely affect the health of humans. CONCLUSION: Given the established benefits of UV protection, the use of sunscreens remains an important part of an overall photoprotective strategy. Future sunscreens with improved formulation should ideally offer superior protection. With increased usage of sunscreen by the public, continuous and vigilant monitoring of the overall safety of future products is also needed.

Superoxide dismutase 1 (SOD1) is essential for H2O2-mediated oxidation and inactivation of phosphatases in growth factor signaling.

Superoxide dismutase 1 (SOD1) is an abundant copper/zinc enzyme found in the cytoplasm that converts superoxide into hydrogen peroxide and molecular oxygen. Tetrathiomolybdate (ATN-224) has been recently identified as an inhibitor of SOD1 that attenuates FGF-2- and VEGF-mediated phosphorylation of ERK1/2 in endothelial cells. However, the mechanism for this inhibition was not elucidated. Growth factor (GF) signaling elicits an increase in reactive oxygen species (ROS), which inactivates protein tyrosine phosphatases (PTP) by oxidizing an essential cysteine residue in the active site. ATN-224-mediated inhibition of SOD1 in tumor and endothelial cells prevents the formation of sufficiently high levels of H(2)O(2), resulting in the protection of PTPs from H(2)O(2)-mediated oxidation. This, in turn, leads to the inhibition of EGF-, IGF-1-, and FGF-2-mediated phosphorylation of ERK1/2. Pretreatment with exogenous H(2)O(2) or with the phosphatase inhibitor vanadate abrogates the inhibition of ERK1/2 phosphorylation induced by ATN-224 or SOD1 siRNA treatments. Furthermore, ATN-224-mediated SOD1 inhibition causes the down-regulation of the PDGF receptor. SOD1 inhibition also increases the steady-state levels of superoxide, which induces protein oxidation in A431 cells but, surprisingly, does not oxidize phosphatases. Thus, SOD1 inhibition in A431 tumor cells results in both prooxidant effects caused by the increase in the levels of superoxide and antioxidant effects caused by lowering the levels of H(2)O(2). These results identify SOD1 as a master regulator of GF signaling and as a therapeutic target for the inhibition of angiogenesis and tumor growth.

Hypertrophic osteoarthropathy presenting as unilateral cellulitis with successful treatment using pamidronate disodium.

Hypertrophic pulmonary osteoarthropathy is a paraneoplastic syndrome seen in patients with lung cancer. This condition is characterized by the presence of digital clubbing, periosteal thickening, synovial thickening, and severe pain of the affected joints. Other syndromes exhibiting clubbing may or may not have underlying diseases causing their manifestation. An example is primary hypertrophic osteoarthropathy, or pachydermoperiostosis. While clubbing makes up part of the clinical picture in both hypertrophic pulmonary osteoarthropathy and hypertrophic osteoarthropathy, the latter has no underlying disease associations. Rather, primary hypertrophic osteoarthropathy is familial, idiopathic, and has a chronic course often beginning during puberty in males. Secondary hypertrophic osteoarthropathy is an acquired form of clubbing that is classically associated with lung disease. However, it has also been associated with diseases of the heart, liver, and intestines. In the setting of pulmonary malignancy, secondary hypertrophic osteoarthropathy is known as hypertrophic pulmonary osteoarthropathy. Hypertrophic pulmonary osteoarthropathy has a distinct constellation of clinical findings that includes intractable pain often refractory to treatments other than resolution of the underlying disease process. The authors herein report a case of hypertrophic pulmonary osteoarthropathy masquerading as recurrent lower extremity cellulitis with chronic hand and foot pain in the setting of pulmonary malignancy that responded dramatically to intravenous pamidronate disodium (a bisphosphonate). Given the rarity of hypertrophic osteoarthropathy associated with lung cancer and the difficulty with pain management in such circumstances, the authors present the following case in which pain was mitigated by treatment with bisphosphonate therapy.