BACKGROUND: Cutaneous melanoma accounts for 75% of skin cancer deaths. Standard treatment is surgical excision with a safety margin some distance from the borders of the primary tumour. The purpose of the safety margin is to remove both the complete primary tumour and any melanoma cells that might have spread into the surrounding skin. Excision margins are important because there could be trade-off between a better cosmetic result but poorer long-term survival if margins become too narrow. The optimal width of excision margins remains unclear. This uncertainty warrants systematic review. OBJECTIVES: To assess the effects of different excision margins for primary cutaneous melanoma. SEARCH STRATEGY: In August 2009 we searched for relevant randomised trials in the Cochrane Skin Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL) in The Cochrane Library (Issue 3, 2009), Medline, Embase, Lilacs, and other databases including Ongoing Trials Registers. SELECTION CRITERIA: We considered all randomized controlled trials (RCTs) of surgical excision of melanoma comparing different width excision margins. DATA COLLECTION AND ANALYSIS: We assessed trial quality, and extracted and analyzed data on survival and recurrence. We collected adverse effects information from included trials. MAIN RESULTS: We identified five trials. There were 1633 participants in the narrow excision margin group and 1664 in the wide excision margin group. Narrow margin definition ranged from 1 to 2 cm; wide margins ranged from 3 to 5 cm. Median follow-up ranged from 5 to 16 years. AUTHORS' CONCLUSIONS: This systematic review summarises the evidence regarding width of excision margins for primary cutaneous melanoma. None of the five published trials, nor our meta-analysis, showed a statistically significant difference in overall survival between narrow or wide excision. The summary estimate for overall survival favoured wide excision by a small degree [Hazard Ratio 1.04; 95% confidence interval 0.95 to 1.15; P = 0.40], but the result was not significantly different. This result is compatible with both a 5% relative reduction in overall mortality favouring narrower excision and a 15% relative reduction in overall mortality favouring wider excision. Therefore, a small (but potentially important) difference in overall survival between wide and narrow excision margins cannot be confidently ruled out. The summary estimate for recurrence free survival favoured wide excision [Hazard Ratio 1.13; P = 0.06; 95% confidence interval 0.99 to 1.28] but again the result did not reach statistical significance (P < 0.05 level). Current randomized trial evidence is insufficient to address optimal excision margins for primary cutaneous melanoma.
Key points• Effective therapies for acne target one or more pathways in the pathogenesis of acne, and combination therapy gives better results than monotherapy.• Topical therapies are the standard of care for mild to moderate acne.
An appreciation of the adverse cutaneous consequences of smoking is important. Dermatologists can play an integral role in promoting smoking cessation by providing expert opinion and educating the public on the deleterious effects of smoking on the skin.
An appreciation of the adverse cutaneous consequences of smoking is important. Dermatologists can play an integral role in promoting smoking cessation by providing expert opinion and educating the public on the deleterious effects of smoking on the skin.
-In the last fifty years, Clostridium botulinum has become notorious for its ability to produce the deadly botulinum neurotoxins. While botulinum toxin A, better known as Botox™, is universally recognised by the public as a cosmetic enhancement tool, the botulinum neurotoxins are commonly used off-label for many medical conditions in ophthalmology, neurology and dermatology. The versatility of these botulinum toxins has made Clostridium botulinum one of the most widely known bacterial pathogens in medical history. This article outlines the discovery of botulinum toxins through to their present day applications in medicine.KEY WORDS: botulinum toxin, dermatology, food poisoning, human disease, neurology, ophthalmology The botulinum toxinsClostridium botulinum is a rod-shaped, gram-positive anaerobic bacterium. Each of the seven serotypes of this bacterium (A, B, C, D, E, F and G) produce a unique form of botulinum neurotoxin (also designated A to G). 1,2 Types A, B and E are commonly involved in human botulism 3 and found in terrestrial, marine and fresh water environments.Botulinum toxin A, produced by the high yield Hall strain of C botulinum, is the most potent form of botulinum neurotoxin. 4 Botulinum toxin is a high molecular weight protein of 150,000 daltons with noncovalent proteins that protect it from digestive enzymes, thereby making it a highly dangerous food poison. The toxin is destroyed by heating at 80°C for at least one minute.Botulinum toxin A is widely distributed and commercially available as Botox™ (Allergen, Inc) in North America while Dysport™ (Speywood, UK) dominates the European markets. Botulinum toxin B is marketed as Myobloc (Elan Pharmaceuticals) in the USA and Neurobloc (Elan Pharmaceuticals) in Europe; both are currently under review by the US Food and Drug Administration (FDA). 5,6 The FDA specify that Botox™ be distributed in vials of 100±30 mouse units (U) with 1 U equal to the median amount necessary to kill half the sample of mice (LD 50 ). 2,4 Of further note, 1 U of Botox™ is equivalent to 3 ng of botulinum toxin A or 2-5 U Dysport™ (the latter will not be further discussed in this essay). 2 Depending on the medical condition, 30-300 U (1-10 ng) Botox™ injections are required two to six times per year, and administration of the toxin at higher concentrations or too frequently creates the risk of developing antibodies that nullify any beneficial effects. 2 As a pharmaceutical, botulinum toxin A has a large margin of safety with an LD 50 of 3,000 U (100 ng) in humans and side effects from treatment are minimal.All botulinum toxins have a similar mode of action whereby they interfere with the transmission of nerve impulses by inhibiting the release of the acetylcholine neurotransmitter from nerve terminals at the neuromuscular junction. The effect is long lasting but also reversible, as new nerve terminals sprout to replace the formerly inhibited ones. 7,8 Food poisoning from botulinum toxinsIn the late 1700s, botulism, a disease caused by human ingestion of botulinum t...
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