Aesthetic Dermatology

For chronic great saphenous vein insufficiency, endovenous laser ablation is comparably effective and as safe as high ligation with vein stripping, according to a study published online Sept. 19 in the Archives of Dermatology.

In what researchers described as the largest and most powerful randomized clinical trial (RCT) to date comparing an endovenous technique with conventional surgery, the two approaches were "equivalent in terms of the primary objective of clinical recurrence," as well as in almost all of the secondary end points, at 2-year follow-up.

"This major finding is in accordance with those of all of the RCTs published so far comparing EVLT [endovenous laser treatment] and HLS [high ligation with stripping]" of the great saphenous vein, said Dr. Knuth Rass of the department of dermatology, venerology, and allergy, Saarland University Hospital, Homburg, Germany, and his associates.

The investigators reported the 2-year results of the ongoing RELACS (Randomized Study Comparing Endovenous Laser Ablation With Crossectomy and Stripping of the Great Saphenous Vein). The trial enrolled 400 consecutive patients (one treated leg per patient) who were seen at two medical centers in Germany for great saphenous vein insufficiency with saphenofemoral incompetence and reflux at least down to the knee level.

However, 54 subjects dropped out after randomization, mostly because they preferred the treatment to which they were not assigned. So the study analyses were based on the per-protocol population of 185 treated with EVLT and 161 treated with HLS.

The primary end point (the rate of freedom from clinical recurrence) was 84% with EVLT and 77% with HLS, a nonsignificant difference.

Similarly, the recurrence-free rates specifically involving varicose veins originating from the operative site were 97% in both groups, the researchers reported (Arch. Dermatol. 2011 [doi:10.1001/archdermatol.2011.272]).

Also in both groups, the scores on a measure of varicose vein severity declined from baseline to 3 months, declined further from 3-12 months, and remained stable at 12-24 months. Disease-specific quality of life scores improved significantly and to the same degree in both groups, with no differences in subscores on pain, physical well-being, psychological well-being, or social well-being.

There were no significant differences between the two groups in the rate of major complications, which was 1.1% overall. These included one case of GI bleeding in the EVLT group, which was related to the use of low-molecular-weight heparin and oral ibuprofen, and two cases of thrombus propagation into the common femoral vein, also in the EVLT group.

Minor adverse effects were frequent but mild in both groups. "Phlebitic reactions, indurations, dyspigmentations, and pain incidence and intensity were more pronounced in the EVLT group. [But] pain persisted longer after HLS," noted the investigators. Bruising and dysesthesia were the same in both groups.

A "remarkable" 98% of both groups said they were satisfied with treatment and would undergo each procedure again if medically necessary.

The two treatment approaches did differ in the incidence of recurrences at the saphenofemoral junction as detected on duplex ultrasonography. These recurrence-free rates were 82% with EVLT and 99% with HLS. However, this difference had no apparent effect on clinical or functional outcome.

"Currently, it remains speculative as to if, when, and to what extent the duplex-detected refluxes at the saphenofemoral junction evolve to a clinical recurrence. ... Further follow-up to 5 years after treatment is scheduled for this study and will probably provide more evidence on this topic," Dr. Rass and his associates wrote.

No conflicts of interest were reported.

For chronic great saphenous vein insufficiency, endovenous laser ablation is comparably effective and as safe as high ligation with vein stripping, according to a study published online Sept. 19 in the Archives of Dermatology.

In what researchers described as the largest and most powerful randomized clinical trial (RCT) to date comparing an endovenous technique with conventional surgery, the two approaches were "equivalent in terms of the primary objective of clinical recurrence," as well as in almost all of the secondary end points, at 2-year follow-up.

"This major finding is in accordance with those of all of the RCTs published so far comparing EVLT [endovenous laser treatment] and HLS [high ligation with stripping]" of the great saphenous vein, said Dr. Knuth Rass of the department of dermatology, venerology, and allergy, Saarland University Hospital, Homburg, Germany, and his associates.

The investigators reported the 2-year results of the ongoing RELACS (Randomized Study Comparing Endovenous Laser Ablation With Crossectomy and Stripping of the Great Saphenous Vein). The trial enrolled 400 consecutive patients (one treated leg per patient) who were seen at two medical centers in Germany for great saphenous vein insufficiency with saphenofemoral incompetence and reflux at least down to the knee level.

However, 54 subjects dropped out after randomization, mostly because they preferred the treatment to which they were not assigned. So the study analyses were based on the per-protocol population of 185 treated with EVLT and 161 treated with HLS.

The primary end point (the rate of freedom from clinical recurrence) was 84% with EVLT and 77% with HLS, a nonsignificant difference.

Similarly, the recurrence-free rates specifically involving varicose veins originating from the operative site were 97% in both groups, the researchers reported (Arch. Dermatol. 2011 [doi:10.1001/archdermatol.2011.272]).

Also in both groups, the scores on a measure of varicose vein severity declined from baseline to 3 months, declined further from 3-12 months, and remained stable at 12-24 months. Disease-specific quality of life scores improved significantly and to the same degree in both groups, with no differences in subscores on pain, physical well-being, psychological well-being, or social well-being.

There were no significant differences between the two groups in the rate of major complications, which was 1.1% overall. These included one case of GI bleeding in the EVLT group, which was related to the use of low-molecular-weight heparin and oral ibuprofen, and two cases of thrombus propagation into the common femoral vein, also in the EVLT group.

Minor adverse effects were frequent but mild in both groups. "Phlebitic reactions, indurations, dyspigmentations, and pain incidence and intensity were more pronounced in the EVLT group. [But] pain persisted longer after HLS," noted the investigators. Bruising and dysesthesia were the same in both groups.

A "remarkable" 98% of both groups said they were satisfied with treatment and would undergo each procedure again if medically necessary.

The two treatment approaches did differ in the incidence of recurrences at the saphenofemoral junction as detected on duplex ultrasonography. These recurrence-free rates were 82% with EVLT and 99% with HLS. However, this difference had no apparent effect on clinical or functional outcome.

"Currently, it remains speculative as to if, when, and to what extent the duplex-detected refluxes at the saphenofemoral junction evolve to a clinical recurrence. ... Further follow-up to 5 years after treatment is scheduled for this study and will probably provide more evidence on this topic," Dr. Rass and his associates wrote.

No conflicts of interest were reported.

For chronic great saphenous vein insufficiency, endovenous laser ablation is comparably effective and as safe as high ligation with vein stripping, according to a study published online Sept. 19 in the Archives of Dermatology.

In what researchers described as the largest and most powerful randomized clinical trial (RCT) to date comparing an endovenous technique with conventional surgery, the two approaches were "equivalent in terms of the primary objective of clinical recurrence," as well as in almost all of the secondary end points, at 2-year follow-up.

"This major finding is in accordance with those of all of the RCTs published so far comparing EVLT [endovenous laser treatment] and HLS [high ligation with stripping]" of the great saphenous vein, said Dr. Knuth Rass of the department of dermatology, venerology, and allergy, Saarland University Hospital, Homburg, Germany, and his associates.

The investigators reported the 2-year results of the ongoing RELACS (Randomized Study Comparing Endovenous Laser Ablation With Crossectomy and Stripping of the Great Saphenous Vein). The trial enrolled 400 consecutive patients (one treated leg per patient) who were seen at two medical centers in Germany for great saphenous vein insufficiency with saphenofemoral incompetence and reflux at least down to the knee level.

However, 54 subjects dropped out after randomization, mostly because they preferred the treatment to which they were not assigned. So the study analyses were based on the per-protocol population of 185 treated with EVLT and 161 treated with HLS.

The primary end point (the rate of freedom from clinical recurrence) was 84% with EVLT and 77% with HLS, a nonsignificant difference.

Similarly, the recurrence-free rates specifically involving varicose veins originating from the operative site were 97% in both groups, the researchers reported (Arch. Dermatol. 2011 [doi:10.1001/archdermatol.2011.272]).

Also in both groups, the scores on a measure of varicose vein severity declined from baseline to 3 months, declined further from 3-12 months, and remained stable at 12-24 months. Disease-specific quality of life scores improved significantly and to the same degree in both groups, with no differences in subscores on pain, physical well-being, psychological well-being, or social well-being.

There were no significant differences between the two groups in the rate of major complications, which was 1.1% overall. These included one case of GI bleeding in the EVLT group, which was related to the use of low-molecular-weight heparin and oral ibuprofen, and two cases of thrombus propagation into the common femoral vein, also in the EVLT group.

Minor adverse effects were frequent but mild in both groups. "Phlebitic reactions, indurations, dyspigmentations, and pain incidence and intensity were more pronounced in the EVLT group. [But] pain persisted longer after HLS," noted the investigators. Bruising and dysesthesia were the same in both groups.

A "remarkable" 98% of both groups said they were satisfied with treatment and would undergo each procedure again if medically necessary.

The two treatment approaches did differ in the incidence of recurrences at the saphenofemoral junction as detected on duplex ultrasonography. These recurrence-free rates were 82% with EVLT and 99% with HLS. However, this difference had no apparent effect on clinical or functional outcome.

"Currently, it remains speculative as to if, when, and to what extent the duplex-detected refluxes at the saphenofemoral junction evolve to a clinical recurrence. ... Further follow-up to 5 years after treatment is scheduled for this study and will probably provide more evidence on this topic," Dr. Rass and his associates wrote.

No conflicts of interest were reported.

Feverfew, a member of the Asteraceae or Compositae family, is a perennial herb with a long history of traditional use.

The expression "feverfew" is derived from the Latin for fever reducer. Evidence of the anti-inflammatory properties of feverfew has been accruing over the last several decades and is now considered well established (Carcinogenesis 2004;25:1449-58).

Photo (c)Courtesy Wikimedia Commons/Dr Paul G Tuli/Creative Commons License

In a Medline literature review of herbal agents that many people take but that might warrant discontinuing before dermatologic surgery, authors cited feverfew for its known success as a treatment for migraines (Br. Med. J. [Clin. Res. Ed.] 1985;291:569-73). In addition, feverfew is known for success in treatment for arthritis, as well as its anti-inflammatory activity in blocking phospholipase breakdown of arachidonic acid into prostaglandins and leukotrienes (Dermatol. Surg. 2001;27:759-63; Prostaglandins Leukot. Med. 1982;8:653-60).

They noted that platelet aggregation is also induced by the feverfew extract parthenolide and a byproduct of the arachidonic acid cascade, thromboxane A (Dermatol. Surg. 2001;27:759-63; J. Pharm. Pharmacol. 1990;42:553-7; J. Pharm. Pharmacol. 1987;39:459-65). Parthenolide is obtained as a hydroalcoholic extract of aerial parts of the plant, and is known to inhibit nuclear factor–kappaB (NF-kappaB) and to exhibit antiproliferative properties (Biochem. Biophys. Res. Commun. 2005;332:321-5). Feverfew also contains the potent antioxidant melatonin (Lancet 1997;350:1598-9).

Parthenolide Potency

Parthenolide has been consistently shown to exhibit in vitro antitumor activity (Mol. Cancer Ther. 2005;4:1004-12). A recent in vitro and in vivo investigation of the cancer chemopreventive potential of parthenolide using the UVB-induced skin cancer model revealed that SKH-1 hairless mice that were given parthenolide exhibited later onset of papillomas and significantly fewer papillomas in comparison to mice that were exposed only to UVB but not fed the primary component of feverfew. The in vitro phase of the study, which used cultured JB6 murine epidermal cells, showed that noncytotoxic concentrations of parthenolide pretreatment significantly suppressed UVB-induced activator protein-1 DNA binding and transcriptional activity, as well as JNK (c-Jun N-terminal kinase) and p38 MAP (mitogen-activated protein) kinase signaling activation, all of which might be crucial in the anticancer mechanism of action of parthenolide, according to the authors (Carcinogenesis 2004;25:1449-58). In a study conducted by three of the same investigators, parthenolide was found to sensitize UVB-induced apoptosis through pathways that depend on protein kinase C (Carcinogenesis 2005;26:2149-56).

In another recent study, investigators found that parthenolide effectively blocked the gene expression mediated by NF-kappaB and the production of bFGF (basic fibroblast growth factor) and MMP-1 (matrix metalloprotease-1) as well as the UVB-induced proliferation of keratinocytes and melanocytes in mouse skin, prompting the conclusion that inhibitors of NF-kappaB, particularly parthenolide, have potential to prevent cutaneous photoaging (J. Pharmacol. Exp. Ther. 2005;315:624-30).

In addition to its potential activity against skin cancer and photoaging, the feverfew constituent parthenolide confers other benefits pertinent to dermatology. Researchers recently identified potent intracellular antioxidant activity displayed by parthenolide in hippocampal HT22 cells, properties that are mediated by an increase of glutathione but not found to mediate the sesquiterpene lactone’s antiproliferative activities or its suppression of NF-kappaB (Biochem. Biophys. Res. Commun. 2005;332:321-5).

Parthenolide has also shown marked leishmanicidal activities suitable enough, according to investigators, to be considered for inclusion in the development of new drugs to treat this disease (Antimicrob. Agents Chemother. 2005;49:176-82).

Although several in vitro studies have indicated that parthenolide imparts anti-inflammatory effects, a recent in vivo study with mice demonstrated that the sesquiterpene lactone component of feverfew modestly suppressed only one gene, interleukin-6 after lipopolysaccharide-induced increases (J. Inflamm. (Lond). 2005;2:6). The authors concluded that more study of the effects of parthenolide and other herbal constituents on inflammatory gene expression using animal models is needed to assess the efficacy of various supplements.

A recent finding regarding parthenolide indicates the expanding breadth and depth of the potential medical applications of this herbal extract. Parthenolide was recently found to exhibit significant activity in suppressing hepatitis C virus, which is often a precursor to cirrhosis and hepatocellular carcinoma (J. Inflamm. [Lond]. 2005;2:6). In hepatoma cells, parthenolide has been found to enhance the apoptosis induced by fenretinide (N-4-hydroxyphenyl retinamide, or 4-HPR), a synthetic anticancer retinoid and an established apoptosis-inducing agent. In a study focusing on the relationship of these two compounds, parthenolide was found to upregulate or downregulate 35 apoptosis-related genes, and its role as an adjuvant anticancer agent against hepatoma was elucidated (Cancer Res. 2005;65:2804-14).

Parthenolide has demonstrated potential activity against several other cancer types. The herbal compound has been found to preferentially induce apoptosis in acute myelogenous leukemia stem cells without adversely affecting normal blood cells (Expert Opin. Biol. Ther. 2005;5:1147-52). In a recent study, parthenolide dose-dependently induced apoptosis in all four cholangiocarcinoma cell lines with sarcomatous SCK cells more sensitive to parthenolide than the other adenomatous cholangiocarcinoma cells. Investigation of the greater susceptibility of SCK cells to parthenolide revealed Bcl-2 family molecular involvement, and indicated that impaired expression of Bcl-X(L) might play a role in the greater sensitivity of SCK cells, compared with other adenomatous cholangiocarcinoma cells, to parthenolide (Cancer Res. 2005;65:6312-20).

In a study of the effects of parthenolide in three human pancreatic tumor cell lines (BxPC-3, PANC-1, and MIA PaCa-2), the sesquiterpene lactone dose-dependently inhibited cancer cell growth in all three lines as well as the level of NF-kappaB inhibitory protein I kappa B-alpha, and reduced NF-kappaB DNA binding activity. Investigators also found that combining parthenolide treatment of cells with the NSAID sulindac synergistically suppressed cell growth in MIA PaCa-2 and BxPC-3 cells and cumulatively in PANC-1 cells and reduced the apoptosis threshold. The combined treatment also increased I kappa B-alpha levels and decreased NF-kappaB DNA binding and transcriptional activities more than the compounds alone. The researchers concluded that parthenolide is a viable NF-kappaB inhibitor to be used in combination with an NSAID to treat pancreatic adenocarcinoma (Mol. Cancer Ther. 2005;4:587-94).

In 2010, Tanaka et al. found that the NF-kappaB inhibitors parthenolide and magnolol can effectively block NF-kappaB–mediated gene expression, as well as UVB-induced proliferation of keratinocytes and melanocytes in murine skin, suggesting that both compounds may play a role in preventing photoaging (Curr. Drug Metab. 2010;11:431-5).

Parthenolide has also been demonstrated in an in vitro MDA-MB-231 cell-derived xenograft metastasis model of breast cancer to be effective alone or combined with docetaxel in decreasing colony formation, as well as inducing apoptosis and reducing the expression of prometastatic genes IL-8 and the antiapoptotic gene GADD45beta1. Combining the treatments also enhanced survival for animal subjects, compared with untreated animals or those treated with either agent alone. The combination was also linked to diminished lung metastases. Animals that were treated with either or both agents were found to have lower NF-kappaB levels in residual tumors and lung metastases. Investigators suggest that these findings are the first to show that parthenolide exhibits significant in vivo chemosensitizing activity in a metastatic breast cancer environment (Mol. Cancer Ther. 2005;4:1004-12).

Recently, investigators studied the anticancer effects of parthenolide in melanoma cells in vitro, in melanoma cell lines and melanocytes, and in melanoma cells obtained from a surgical excision, finding that the herbal compound decreased the number of viable adherent cells in melanoma cultures. The researchers also noted that preincubation of parthenolide with the thiol nucleophile N-acetylcysteine shielded melanoma cells from parthenolide-induced cell death, implying that the mechanism attributable to parthenolide activity is the reaction with intracellular thiols. They concluded that the apparent anticancer activity of parthenolide warrants further evaluation for melanoma therapy (Melanoma Res. 2010;20:21-34).

Problems with Parthenolide and Parthenolide-Free Feverfew

The Compositae family is known to cause contact dermatitis in susceptible individuals, and Compositae allergy is among the top 10 contact sensitivities in Europe. Sesquiterpene lactones are considered to be the primary sensitizers (Med. Pregl. 2003;56:43-9). Indeed, parthenolide has become known as a potent skin sensitizer (Inflammopharmacology 2009;17:42-9). When feverfew is ingested orally for migraines, oral ulcers have been reported. Feverfew has many benefits that are not derived from parthenolide. Researchers found that a form of feverfew had the parthenolide portion removed, and therefore could be used more safely as a topical ingredient.

In 2008, Martin et al. established the in vitro and in vivo antioxidant efficacy of a parthenolide-depleted feverfew extract. Shown to exhibit greater activity than vitamin C, the extract restored cigarette smoke–mediated depletion of cellular thiols, diminished the formation of UV-induced hydrogen peroxide, and inhibited proinflammatory cytokine release in vitro. In addition, the topical formulation decreased UV-induced epidermal hyperplasia, DNA damage, and apoptosis in vivo. Finally, a clinical study of the extract revealed that treatment significantly reduced UV-induced erythema vs. placebo 24 hours after exposure. Consequently, the researchers expressed confidence in their parthenolide-depleted feverfew formulation to protect the skin from exogenous oxidizing influences (Arch. Dermatol. Res. 2008;300:69-80).

In 2009, some of the same investigators assessed the anti-inflammatory capacity of the parthenolide-depleted feverfew extract that they developed. In vitro, the extract hindered the activity of several proinflammatory enzymes (that is, 5-lipoxygenase, phosphodiesterase-3, and phosphodiesterase-4), as well as the release of proinflammatory mediators. In vivo, the extract thwarted oxazolone-induced dermatitis and was more effective than regular feverfew in treating TPA (12-O-tetradecanoylphorbol 13-acetate)–induced dermatitis. In a clinical assessment, the investigators found that their extract diminished erythema in a methyl nicotinate-induced vasodilation model. They concluded that the parthenolide-depleted feverfew extract exhibits strong anti-inflammatory activity but without the accompanying sensitizing activity characteristic of whole feverfew (Inflammopharmacology 2009;17:42-9).

Some sensitivity to these agents may still arise, however. In 2010, Paulsen et al. investigated the tolerance of individuals with contact allergy to feverfew using patch tests with new parthenolide-depleted feverfew formulations in a small study with seven patients. Subjects were patch tested with two parthenolide-depleted creams. The researchers noted that four patients tested positive to one of the agents, and reactivity was linked to simultaneous positive response to parthenolide. Two years later, they analyzed this cream, finding no parthenolide, which they ascribed to degradation of the compound (Contact Dermatitis 2010;63:146-50).

Conclusion

Feverfew is best known as an effective herbal alternative for treating migraine headaches. New evidence is emerging that numerous other health benefits might be derived from this plant, and particularly its chief component parthenolide. The findings regarding anticarcinogenic and anti-inflammatory capacity are promising and may soon have dermatologic implications.

Formulations must be developed to account for the allergenic potential of parthenolide. Recent success has been observed with parthenolide-depleted feverfew. The ability to take a naturally occurring ingredient and improve it by removing an undesirable part of the chemical structure is the future of "natural" skin care, in my opinion. Will we be seeing more of the tweaked ingredients? I believe we will.

Feverfew, a member of the Asteraceae or Compositae family, is a perennial herb with a long history of traditional use.

The expression "feverfew" is derived from the Latin for fever reducer. Evidence of the anti-inflammatory properties of feverfew has been accruing over the last several decades and is now considered well established (Carcinogenesis 2004;25:1449-58).

Photo (c)Courtesy Wikimedia Commons/Dr Paul G Tuli/Creative Commons License

In a Medline literature review of herbal agents that many people take but that might warrant discontinuing before dermatologic surgery, authors cited feverfew for its known success as a treatment for migraines (Br. Med. J. [Clin. Res. Ed.] 1985;291:569-73). In addition, feverfew is known for success in treatment for arthritis, as well as its anti-inflammatory activity in blocking phospholipase breakdown of arachidonic acid into prostaglandins and leukotrienes (Dermatol. Surg. 2001;27:759-63; Prostaglandins Leukot. Med. 1982;8:653-60).

They noted that platelet aggregation is also induced by the feverfew extract parthenolide and a byproduct of the arachidonic acid cascade, thromboxane A (Dermatol. Surg. 2001;27:759-63; J. Pharm. Pharmacol. 1990;42:553-7; J. Pharm. Pharmacol. 1987;39:459-65). Parthenolide is obtained as a hydroalcoholic extract of aerial parts of the plant, and is known to inhibit nuclear factor–kappaB (NF-kappaB) and to exhibit antiproliferative properties (Biochem. Biophys. Res. Commun. 2005;332:321-5). Feverfew also contains the potent antioxidant melatonin (Lancet 1997;350:1598-9).

Parthenolide Potency

Parthenolide has been consistently shown to exhibit in vitro antitumor activity (Mol. Cancer Ther. 2005;4:1004-12). A recent in vitro and in vivo investigation of the cancer chemopreventive potential of parthenolide using the UVB-induced skin cancer model revealed that SKH-1 hairless mice that were given parthenolide exhibited later onset of papillomas and significantly fewer papillomas in comparison to mice that were exposed only to UVB but not fed the primary component of feverfew. The in vitro phase of the study, which used cultured JB6 murine epidermal cells, showed that noncytotoxic concentrations of parthenolide pretreatment significantly suppressed UVB-induced activator protein-1 DNA binding and transcriptional activity, as well as JNK (c-Jun N-terminal kinase) and p38 MAP (mitogen-activated protein) kinase signaling activation, all of which might be crucial in the anticancer mechanism of action of parthenolide, according to the authors (Carcinogenesis 2004;25:1449-58). In a study conducted by three of the same investigators, parthenolide was found to sensitize UVB-induced apoptosis through pathways that depend on protein kinase C (Carcinogenesis 2005;26:2149-56).

In another recent study, investigators found that parthenolide effectively blocked the gene expression mediated by NF-kappaB and the production of bFGF (basic fibroblast growth factor) and MMP-1 (matrix metalloprotease-1) as well as the UVB-induced proliferation of keratinocytes and melanocytes in mouse skin, prompting the conclusion that inhibitors of NF-kappaB, particularly parthenolide, have potential to prevent cutaneous photoaging (J. Pharmacol. Exp. Ther. 2005;315:624-30).

In addition to its potential activity against skin cancer and photoaging, the feverfew constituent parthenolide confers other benefits pertinent to dermatology. Researchers recently identified potent intracellular antioxidant activity displayed by parthenolide in hippocampal HT22 cells, properties that are mediated by an increase of glutathione but not found to mediate the sesquiterpene lactone’s antiproliferative activities or its suppression of NF-kappaB (Biochem. Biophys. Res. Commun. 2005;332:321-5).

Parthenolide has also shown marked leishmanicidal activities suitable enough, according to investigators, to be considered for inclusion in the development of new drugs to treat this disease (Antimicrob. Agents Chemother. 2005;49:176-82).

Although several in vitro studies have indicated that parthenolide imparts anti-inflammatory effects, a recent in vivo study with mice demonstrated that the sesquiterpene lactone component of feverfew modestly suppressed only one gene, interleukin-6 after lipopolysaccharide-induced increases (J. Inflamm. (Lond). 2005;2:6). The authors concluded that more study of the effects of parthenolide and other herbal constituents on inflammatory gene expression using animal models is needed to assess the efficacy of various supplements.

A recent finding regarding parthenolide indicates the expanding breadth and depth of the potential medical applications of this herbal extract. Parthenolide was recently found to exhibit significant activity in suppressing hepatitis C virus, which is often a precursor to cirrhosis and hepatocellular carcinoma (J. Inflamm. [Lond]. 2005;2:6). In hepatoma cells, parthenolide has been found to enhance the apoptosis induced by fenretinide (N-4-hydroxyphenyl retinamide, or 4-HPR), a synthetic anticancer retinoid and an established apoptosis-inducing agent. In a study focusing on the relationship of these two compounds, parthenolide was found to upregulate or downregulate 35 apoptosis-related genes, and its role as an adjuvant anticancer agent against hepatoma was elucidated (Cancer Res. 2005;65:2804-14).

Parthenolide has demonstrated potential activity against several other cancer types. The herbal compound has been found to preferentially induce apoptosis in acute myelogenous leukemia stem cells without adversely affecting normal blood cells (Expert Opin. Biol. Ther. 2005;5:1147-52). In a recent study, parthenolide dose-dependently induced apoptosis in all four cholangiocarcinoma cell lines with sarcomatous SCK cells more sensitive to parthenolide than the other adenomatous cholangiocarcinoma cells. Investigation of the greater susceptibility of SCK cells to parthenolide revealed Bcl-2 family molecular involvement, and indicated that impaired expression of Bcl-X(L) might play a role in the greater sensitivity of SCK cells, compared with other adenomatous cholangiocarcinoma cells, to parthenolide (Cancer Res. 2005;65:6312-20).

In a study of the effects of parthenolide in three human pancreatic tumor cell lines (BxPC-3, PANC-1, and MIA PaCa-2), the sesquiterpene lactone dose-dependently inhibited cancer cell growth in all three lines as well as the level of NF-kappaB inhibitory protein I kappa B-alpha, and reduced NF-kappaB DNA binding activity. Investigators also found that combining parthenolide treatment of cells with the NSAID sulindac synergistically suppressed cell growth in MIA PaCa-2 and BxPC-3 cells and cumulatively in PANC-1 cells and reduced the apoptosis threshold. The combined treatment also increased I kappa B-alpha levels and decreased NF-kappaB DNA binding and transcriptional activities more than the compounds alone. The researchers concluded that parthenolide is a viable NF-kappaB inhibitor to be used in combination with an NSAID to treat pancreatic adenocarcinoma (Mol. Cancer Ther. 2005;4:587-94).

In 2010, Tanaka et al. found that the NF-kappaB inhibitors parthenolide and magnolol can effectively block NF-kappaB–mediated gene expression, as well as UVB-induced proliferation of keratinocytes and melanocytes in murine skin, suggesting that both compounds may play a role in preventing photoaging (Curr. Drug Metab. 2010;11:431-5).

Parthenolide has also been demonstrated in an in vitro MDA-MB-231 cell-derived xenograft metastasis model of breast cancer to be effective alone or combined with docetaxel in decreasing colony formation, as well as inducing apoptosis and reducing the expression of prometastatic genes IL-8 and the antiapoptotic gene GADD45beta1. Combining the treatments also enhanced survival for animal subjects, compared with untreated animals or those treated with either agent alone. The combination was also linked to diminished lung metastases. Animals that were treated with either or both agents were found to have lower NF-kappaB levels in residual tumors and lung metastases. Investigators suggest that these findings are the first to show that parthenolide exhibits significant in vivo chemosensitizing activity in a metastatic breast cancer environment (Mol. Cancer Ther. 2005;4:1004-12).

Recently, investigators studied the anticancer effects of parthenolide in melanoma cells in vitro, in melanoma cell lines and melanocytes, and in melanoma cells obtained from a surgical excision, finding that the herbal compound decreased the number of viable adherent cells in melanoma cultures. The researchers also noted that preincubation of parthenolide with the thiol nucleophile N-acetylcysteine shielded melanoma cells from parthenolide-induced cell death, implying that the mechanism attributable to parthenolide activity is the reaction with intracellular thiols. They concluded that the apparent anticancer activity of parthenolide warrants further evaluation for melanoma therapy (Melanoma Res. 2010;20:21-34).

Problems with Parthenolide and Parthenolide-Free Feverfew

The Compositae family is known to cause contact dermatitis in susceptible individuals, and Compositae allergy is among the top 10 contact sensitivities in Europe. Sesquiterpene lactones are considered to be the primary sensitizers (Med. Pregl. 2003;56:43-9). Indeed, parthenolide has become known as a potent skin sensitizer (Inflammopharmacology 2009;17:42-9). When feverfew is ingested orally for migraines, oral ulcers have been reported. Feverfew has many benefits that are not derived from parthenolide. Researchers found that a form of feverfew had the parthenolide portion removed, and therefore could be used more safely as a topical ingredient.

In 2008, Martin et al. established the in vitro and in vivo antioxidant efficacy of a parthenolide-depleted feverfew extract. Shown to exhibit greater activity than vitamin C, the extract restored cigarette smoke–mediated depletion of cellular thiols, diminished the formation of UV-induced hydrogen peroxide, and inhibited proinflammatory cytokine release in vitro. In addition, the topical formulation decreased UV-induced epidermal hyperplasia, DNA damage, and apoptosis in vivo. Finally, a clinical study of the extract revealed that treatment significantly reduced UV-induced erythema vs. placebo 24 hours after exposure. Consequently, the researchers expressed confidence in their parthenolide-depleted feverfew formulation to protect the skin from exogenous oxidizing influences (Arch. Dermatol. Res. 2008;300:69-80).

In 2009, some of the same investigators assessed the anti-inflammatory capacity of the parthenolide-depleted feverfew extract that they developed. In vitro, the extract hindered the activity of several proinflammatory enzymes (that is, 5-lipoxygenase, phosphodiesterase-3, and phosphodiesterase-4), as well as the release of proinflammatory mediators. In vivo, the extract thwarted oxazolone-induced dermatitis and was more effective than regular feverfew in treating TPA (12-O-tetradecanoylphorbol 13-acetate)–induced dermatitis. In a clinical assessment, the investigators found that their extract diminished erythema in a methyl nicotinate-induced vasodilation model. They concluded that the parthenolide-depleted feverfew extract exhibits strong anti-inflammatory activity but without the accompanying sensitizing activity characteristic of whole feverfew (Inflammopharmacology 2009;17:42-9).

Some sensitivity to these agents may still arise, however. In 2010, Paulsen et al. investigated the tolerance of individuals with contact allergy to feverfew using patch tests with new parthenolide-depleted feverfew formulations in a small study with seven patients. Subjects were patch tested with two parthenolide-depleted creams. The researchers noted that four patients tested positive to one of the agents, and reactivity was linked to simultaneous positive response to parthenolide. Two years later, they analyzed this cream, finding no parthenolide, which they ascribed to degradation of the compound (Contact Dermatitis 2010;63:146-50).

Conclusion

Feverfew is best known as an effective herbal alternative for treating migraine headaches. New evidence is emerging that numerous other health benefits might be derived from this plant, and particularly its chief component parthenolide. The findings regarding anticarcinogenic and anti-inflammatory capacity are promising and may soon have dermatologic implications.

Formulations must be developed to account for the allergenic potential of parthenolide. Recent success has been observed with parthenolide-depleted feverfew. The ability to take a naturally occurring ingredient and improve it by removing an undesirable part of the chemical structure is the future of "natural" skin care, in my opinion. Will we be seeing more of the tweaked ingredients? I believe we will.

Feverfew, a member of the Asteraceae or Compositae family, is a perennial herb with a long history of traditional use.

The expression "feverfew" is derived from the Latin for fever reducer. Evidence of the anti-inflammatory properties of feverfew has been accruing over the last several decades and is now considered well established (Carcinogenesis 2004;25:1449-58).

Photo (c)Courtesy Wikimedia Commons/Dr Paul G Tuli/Creative Commons License

In a Medline literature review of herbal agents that many people take but that might warrant discontinuing before dermatologic surgery, authors cited feverfew for its known success as a treatment for migraines (Br. Med. J. [Clin. Res. Ed.] 1985;291:569-73). In addition, feverfew is known for success in treatment for arthritis, as well as its anti-inflammatory activity in blocking phospholipase breakdown of arachidonic acid into prostaglandins and leukotrienes (Dermatol. Surg. 2001;27:759-63; Prostaglandins Leukot. Med. 1982;8:653-60).

They noted that platelet aggregation is also induced by the feverfew extract parthenolide and a byproduct of the arachidonic acid cascade, thromboxane A (Dermatol. Surg. 2001;27:759-63; J. Pharm. Pharmacol. 1990;42:553-7; J. Pharm. Pharmacol. 1987;39:459-65). Parthenolide is obtained as a hydroalcoholic extract of aerial parts of the plant, and is known to inhibit nuclear factor–kappaB (NF-kappaB) and to exhibit antiproliferative properties (Biochem. Biophys. Res. Commun. 2005;332:321-5). Feverfew also contains the potent antioxidant melatonin (Lancet 1997;350:1598-9).

Parthenolide Potency

Parthenolide has been consistently shown to exhibit in vitro antitumor activity (Mol. Cancer Ther. 2005;4:1004-12). A recent in vitro and in vivo investigation of the cancer chemopreventive potential of parthenolide using the UVB-induced skin cancer model revealed that SKH-1 hairless mice that were given parthenolide exhibited later onset of papillomas and significantly fewer papillomas in comparison to mice that were exposed only to UVB but not fed the primary component of feverfew. The in vitro phase of the study, which used cultured JB6 murine epidermal cells, showed that noncytotoxic concentrations of parthenolide pretreatment significantly suppressed UVB-induced activator protein-1 DNA binding and transcriptional activity, as well as JNK (c-Jun N-terminal kinase) and p38 MAP (mitogen-activated protein) kinase signaling activation, all of which might be crucial in the anticancer mechanism of action of parthenolide, according to the authors (Carcinogenesis 2004;25:1449-58). In a study conducted by three of the same investigators, parthenolide was found to sensitize UVB-induced apoptosis through pathways that depend on protein kinase C (Carcinogenesis 2005;26:2149-56).

In another recent study, investigators found that parthenolide effectively blocked the gene expression mediated by NF-kappaB and the production of bFGF (basic fibroblast growth factor) and MMP-1 (matrix metalloprotease-1) as well as the UVB-induced proliferation of keratinocytes and melanocytes in mouse skin, prompting the conclusion that inhibitors of NF-kappaB, particularly parthenolide, have potential to prevent cutaneous photoaging (J. Pharmacol. Exp. Ther. 2005;315:624-30).

In addition to its potential activity against skin cancer and photoaging, the feverfew constituent parthenolide confers other benefits pertinent to dermatology. Researchers recently identified potent intracellular antioxidant activity displayed by parthenolide in hippocampal HT22 cells, properties that are mediated by an increase of glutathione but not found to mediate the sesquiterpene lactone’s antiproliferative activities or its suppression of NF-kappaB (Biochem. Biophys. Res. Commun. 2005;332:321-5).

Parthenolide has also shown marked leishmanicidal activities suitable enough, according to investigators, to be considered for inclusion in the development of new drugs to treat this disease (Antimicrob. Agents Chemother. 2005;49:176-82).

Although several in vitro studies have indicated that parthenolide imparts anti-inflammatory effects, a recent in vivo study with mice demonstrated that the sesquiterpene lactone component of feverfew modestly suppressed only one gene, interleukin-6 after lipopolysaccharide-induced increases (J. Inflamm. (Lond). 2005;2:6). The authors concluded that more study of the effects of parthenolide and other herbal constituents on inflammatory gene expression using animal models is needed to assess the efficacy of various supplements.

A recent finding regarding parthenolide indicates the expanding breadth and depth of the potential medical applications of this herbal extract. Parthenolide was recently found to exhibit significant activity in suppressing hepatitis C virus, which is often a precursor to cirrhosis and hepatocellular carcinoma (J. Inflamm. [Lond]. 2005;2:6). In hepatoma cells, parthenolide has been found to enhance the apoptosis induced by fenretinide (N-4-hydroxyphenyl retinamide, or 4-HPR), a synthetic anticancer retinoid and an established apoptosis-inducing agent. In a study focusing on the relationship of these two compounds, parthenolide was found to upregulate or downregulate 35 apoptosis-related genes, and its role as an adjuvant anticancer agent against hepatoma was elucidated (Cancer Res. 2005;65:2804-14).

Parthenolide has demonstrated potential activity against several other cancer types. The herbal compound has been found to preferentially induce apoptosis in acute myelogenous leukemia stem cells without adversely affecting normal blood cells (Expert Opin. Biol. Ther. 2005;5:1147-52). In a recent study, parthenolide dose-dependently induced apoptosis in all four cholangiocarcinoma cell lines with sarcomatous SCK cells more sensitive to parthenolide than the other adenomatous cholangiocarcinoma cells. Investigation of the greater susceptibility of SCK cells to parthenolide revealed Bcl-2 family molecular involvement, and indicated that impaired expression of Bcl-X(L) might play a role in the greater sensitivity of SCK cells, compared with other adenomatous cholangiocarcinoma cells, to parthenolide (Cancer Res. 2005;65:6312-20).

In a study of the effects of parthenolide in three human pancreatic tumor cell lines (BxPC-3, PANC-1, and MIA PaCa-2), the sesquiterpene lactone dose-dependently inhibited cancer cell growth in all three lines as well as the level of NF-kappaB inhibitory protein I kappa B-alpha, and reduced NF-kappaB DNA binding activity. Investigators also found that combining parthenolide treatment of cells with the NSAID sulindac synergistically suppressed cell growth in MIA PaCa-2 and BxPC-3 cells and cumulatively in PANC-1 cells and reduced the apoptosis threshold. The combined treatment also increased I kappa B-alpha levels and decreased NF-kappaB DNA binding and transcriptional activities more than the compounds alone. The researchers concluded that parthenolide is a viable NF-kappaB inhibitor to be used in combination with an NSAID to treat pancreatic adenocarcinoma (Mol. Cancer Ther. 2005;4:587-94).

In 2010, Tanaka et al. found that the NF-kappaB inhibitors parthenolide and magnolol can effectively block NF-kappaB–mediated gene expression, as well as UVB-induced proliferation of keratinocytes and melanocytes in murine skin, suggesting that both compounds may play a role in preventing photoaging (Curr. Drug Metab. 2010;11:431-5).

Parthenolide has also been demonstrated in an in vitro MDA-MB-231 cell-derived xenograft metastasis model of breast cancer to be effective alone or combined with docetaxel in decreasing colony formation, as well as inducing apoptosis and reducing the expression of prometastatic genes IL-8 and the antiapoptotic gene GADD45beta1. Combining the treatments also enhanced survival for animal subjects, compared with untreated animals or those treated with either agent alone. The combination was also linked to diminished lung metastases. Animals that were treated with either or both agents were found to have lower NF-kappaB levels in residual tumors and lung metastases. Investigators suggest that these findings are the first to show that parthenolide exhibits significant in vivo chemosensitizing activity in a metastatic breast cancer environment (Mol. Cancer Ther. 2005;4:1004-12).

Recently, investigators studied the anticancer effects of parthenolide in melanoma cells in vitro, in melanoma cell lines and melanocytes, and in melanoma cells obtained from a surgical excision, finding that the herbal compound decreased the number of viable adherent cells in melanoma cultures. The researchers also noted that preincubation of parthenolide with the thiol nucleophile N-acetylcysteine shielded melanoma cells from parthenolide-induced cell death, implying that the mechanism attributable to parthenolide activity is the reaction with intracellular thiols. They concluded that the apparent anticancer activity of parthenolide warrants further evaluation for melanoma therapy (Melanoma Res. 2010;20:21-34).

Problems with Parthenolide and Parthenolide-Free Feverfew

The Compositae family is known to cause contact dermatitis in susceptible individuals, and Compositae allergy is among the top 10 contact sensitivities in Europe. Sesquiterpene lactones are considered to be the primary sensitizers (Med. Pregl. 2003;56:43-9). Indeed, parthenolide has become known as a potent skin sensitizer (Inflammopharmacology 2009;17:42-9). When feverfew is ingested orally for migraines, oral ulcers have been reported. Feverfew has many benefits that are not derived from parthenolide. Researchers found that a form of feverfew had the parthenolide portion removed, and therefore could be used more safely as a topical ingredient.

In 2008, Martin et al. established the in vitro and in vivo antioxidant efficacy of a parthenolide-depleted feverfew extract. Shown to exhibit greater activity than vitamin C, the extract restored cigarette smoke–mediated depletion of cellular thiols, diminished the formation of UV-induced hydrogen peroxide, and inhibited proinflammatory cytokine release in vitro. In addition, the topical formulation decreased UV-induced epidermal hyperplasia, DNA damage, and apoptosis in vivo. Finally, a clinical study of the extract revealed that treatment significantly reduced UV-induced erythema vs. placebo 24 hours after exposure. Consequently, the researchers expressed confidence in their parthenolide-depleted feverfew formulation to protect the skin from exogenous oxidizing influences (Arch. Dermatol. Res. 2008;300:69-80).

In 2009, some of the same investigators assessed the anti-inflammatory capacity of the parthenolide-depleted feverfew extract that they developed. In vitro, the extract hindered the activity of several proinflammatory enzymes (that is, 5-lipoxygenase, phosphodiesterase-3, and phosphodiesterase-4), as well as the release of proinflammatory mediators. In vivo, the extract thwarted oxazolone-induced dermatitis and was more effective than regular feverfew in treating TPA (12-O-tetradecanoylphorbol 13-acetate)–induced dermatitis. In a clinical assessment, the investigators found that their extract diminished erythema in a methyl nicotinate-induced vasodilation model. They concluded that the parthenolide-depleted feverfew extract exhibits strong anti-inflammatory activity but without the accompanying sensitizing activity characteristic of whole feverfew (Inflammopharmacology 2009;17:42-9).

Some sensitivity to these agents may still arise, however. In 2010, Paulsen et al. investigated the tolerance of individuals with contact allergy to feverfew using patch tests with new parthenolide-depleted feverfew formulations in a small study with seven patients. Subjects were patch tested with two parthenolide-depleted creams. The researchers noted that four patients tested positive to one of the agents, and reactivity was linked to simultaneous positive response to parthenolide. Two years later, they analyzed this cream, finding no parthenolide, which they ascribed to degradation of the compound (Contact Dermatitis 2010;63:146-50).

Conclusion

Feverfew is best known as an effective herbal alternative for treating migraine headaches. New evidence is emerging that numerous other health benefits might be derived from this plant, and particularly its chief component parthenolide. The findings regarding anticarcinogenic and anti-inflammatory capacity are promising and may soon have dermatologic implications.

Formulations must be developed to account for the allergenic potential of parthenolide. Recent success has been observed with parthenolide-depleted feverfew. The ability to take a naturally occurring ingredient and improve it by removing an undesirable part of the chemical structure is the future of "natural" skin care, in my opinion. Will we be seeing more of the tweaked ingredients? I believe we will.

In patients diagnosed with invasive primary cutaneous melanoma, a detailed patient history is crucial, and a thorough examination of the skin and lymph nodes should be performed to help determine the extent of clinical spread of the disease. However, for patients with melanomas of any thickness, baseline blood tests and imaging studies are not recommended because clinical research does not support their use unless suspicious signs and symptoms are present.

Those are two recommendations contained in the American Academy of Dermatology’s updated guidelines for the treatment of primary cutaneous melanoma, which were published online in the Journal of the American Academy of Dermatology. Last updated in 2001, the new guidelines focus on biopsy techniques, pathology, surgical treatment, and long-term follow-up care.

"There are many factors that must be considered when diagnosing and treating melanoma, and these new guidelines offer physicians clinically sound recommendations on how to treat melanoma patients and potentially increase their chance of survival from this deadly disease," AAD President Dr. Ronald L. Moy said in a statement.

A 15-member work group of melanoma experts convened by the AAD and chaired by Dr. Allan C. Halpern of Memorial Sloan-Kettering Cancer Center, New York, and Timothy M. Johnson of the University of Michigan and its Comprehensive Cancer Center, Ann Arbor, reviewed clinical studies and guidelines related to melanoma treatment that appeared in English-language publications between 2000 and 2010. Members of the work group used a 3-point scale to grade evidence, and then developed clinical recommendations on the best available evidence (J. Am. Acad. Dermatol. 2011 Aug. 26 doi: 10.1016/j.jaad.2011.04.031]).

The recommendations were ranked as "A" (recommendation based on consistent and good-quality patient-oriented evidence); "B" (recommendation based on inconsistent or limited-quality patient-oriented evidence); and "C" (recommendation based on consensus, opinion, case studies, or disease-oriented evidence).

The Increased Value of Mitotic Rate

According to Dr. David E. Kent, the most significant change from the 2001 guidelines relates to staging, with mitotic rate replacing Clark level of invasion as the second factor predicting melanoma survival in addition to tumor (Breslow) thickness for tumors 1 mm or smaller in thickness.

Included as a prognostic value in the 2010 American Joint Committee on Cancer staging system to upstage patients with melanoma, the mitotic rate is defined as the number of mitoses in the dermis per mm².

"The placement of mitotic rate has substantial value for dermatologists because the question we get asked often is, ‘What is the risk of this superficial melanoma spreading to other parts of the body, either regionally to the lymph nodes or distantly to other sites?’" said Dr. Kent, a clinical instructor in the division of dermatology at the Medical College of Georgia, Augusta, who was not involved in assembling the guidelines. "With the mitotic rate less than 1 mm², it gives us a little bit more comfort in recommending to the patient that there’s less risk of spread. However, if there were to be a substantial mitotic rate, such as 2 mm², 3 mm², 4 mm², or even higher, that would lead one to consider referring the patient for evaluation for a staging and lymph node biopsy, even though the depth of the lesion is thin."

The guidelines note that there is "strong evidence" to support mitotic rate and two other histologic features as the most important characteristics of the primary tumor to predict outcome. The other features are maximum tumor (Breslow) thickness, which "is measured from the granular layer of the overlying epidermis or base of a superficial ulceration to the deepest malignant cells invading dermis to the nearest 0.1 mm, not including deeper adventitial extension," and the presence or absence of microscopic ulceration, "defined as tumor-induced full thickness loss of epidermis with subjacent dermal tumor and reactive dermal changes."

A complete physical exam is recommended by the work group and "includes looking through the scalp, looking in the mouth, and a genital exam as well," Dr. Kent said. "In our practice we refer women to their gynecologist for that, because 1% of all melanomas are genital. We also recommend that they see their medical ophthalmologist every 2 years because you can get melanomas in different areas of the eye."

Screening blood tests, including serum lactate dehydrogenase, are "insensitive for the detection of metastatic disease," the guidelines state, while the use of routine imaging studies "is limited by a very low yield and the frequent occurrence of false positive findings. Ample evidence exists that a routine chest X-ray is a cost inefficient test for the detection of metastatic disease with a consistent relatively high false positive rate." The guidelines also note that advanced imaging studies such as positron emission tomography and computed tomography have lower sensitivity, compared with sentinel lymph node biopsy (SLNB).

As for follow-up of patients with newly diagnosed cutaneous melanoma, the guidelines recommend an annual visit with a dermatologist at the least, but note that visits may range from every 3-12 months based on a patient’s history and risk factors. "The goal of follow-up is to detect any evidence of local recurrence and to detect any additional primary melanomas that may have developed," Dr. Kent said. "I have several patients that have personally had over three melanomas. One patient has had five. Some high risk patients we see every 3 or 4 months for follow-up."

Sentinel Lymph Node Biopsy and Lentigo Maligna

The work group also addressed non-surgical treatments for lentigo maligna, a topic that was not contained in the older version of the guidelines. For example, while off-label use of topical imiquimod has been proposed for lentigo maligna, "studies are limited by highly variable treatment regimens and lack of long-term follow-up with an average of approximately 18 months," the work group wrote. "Histologic verification following treatment has shown persistent disease in approximately 25% of treated patients and progression to invasive melanoma has been noted. As an adjunctive modality following surgical excision, the efficacy of topical imiquimod has not been established. High cost of treatment, an appropriate low threshold for subsequent biopsy to exclude residual or recurrent disease, and the risk of a severe inflammatory reaction should be taken into account when considering imiquimod."

SLNB is another topic contained in the guidelines for the first time. While the work group acknowledged that SLNB is "not without controversy," it described sentinel lymph node status as "the most important prognostic factor for disease-specific survival of patients with melanoma greater than 1 mm in thickness. Whether early detection of occult nodal disease provides greater regional control has not been definitively shown, but available evidence suggests a lower rate of post-operative complications in patients who underwent completion lymph node dissection for micrometastatic disease detected by SLNB, compared to those who underwent therapeutic lymph node dissection for clinically palpable disease."

The work group acknowledged that "significant gaps" exist in research related to the management of primary cutaneous melanoma, including "standardization of the interpretation of mitotic rate; placebo-controlled trials for the treatment of lentigo maligna; the use and value of dermoscopy and other imaging modalities; the clinical and prognostic significance of the use of biomarkers and mutational analysis; and the use of sentinel lymph node biopsy."

For his part, Dr. Kent predicted that major advances in the treatment of cutaneous melanoma should occur in the coming years. "Melanoma is a very unpredictable disease," he said. "Hopefully sometime in the future, we’ll have biomarkers that will assist physicians in identifying patients who are a greater risk of more aggressive disease, of spread to both regional and distant sites. That area of research is very exciting."

Dr. Kent said that he had no relevant financial disclosures.

In patients diagnosed with invasive primary cutaneous melanoma, a detailed patient history is crucial, and a thorough examination of the skin and lymph nodes should be performed to help determine the extent of clinical spread of the disease. However, for patients with melanomas of any thickness, baseline blood tests and imaging studies are not recommended because clinical research does not support their use unless suspicious signs and symptoms are present.

Those are two recommendations contained in the American Academy of Dermatology’s updated guidelines for the treatment of primary cutaneous melanoma, which were published online in the Journal of the American Academy of Dermatology. Last updated in 2001, the new guidelines focus on biopsy techniques, pathology, surgical treatment, and long-term follow-up care.

"There are many factors that must be considered when diagnosing and treating melanoma, and these new guidelines offer physicians clinically sound recommendations on how to treat melanoma patients and potentially increase their chance of survival from this deadly disease," AAD President Dr. Ronald L. Moy said in a statement.

A 15-member work group of melanoma experts convened by the AAD and chaired by Dr. Allan C. Halpern of Memorial Sloan-Kettering Cancer Center, New York, and Timothy M. Johnson of the University of Michigan and its Comprehensive Cancer Center, Ann Arbor, reviewed clinical studies and guidelines related to melanoma treatment that appeared in English-language publications between 2000 and 2010. Members of the work group used a 3-point scale to grade evidence, and then developed clinical recommendations on the best available evidence (J. Am. Acad. Dermatol. 2011 Aug. 26 doi: 10.1016/j.jaad.2011.04.031]).

The recommendations were ranked as "A" (recommendation based on consistent and good-quality patient-oriented evidence); "B" (recommendation based on inconsistent or limited-quality patient-oriented evidence); and "C" (recommendation based on consensus, opinion, case studies, or disease-oriented evidence).

The Increased Value of Mitotic Rate

According to Dr. David E. Kent, the most significant change from the 2001 guidelines relates to staging, with mitotic rate replacing Clark level of invasion as the second factor predicting melanoma survival in addition to tumor (Breslow) thickness for tumors 1 mm or smaller in thickness.

Included as a prognostic value in the 2010 American Joint Committee on Cancer staging system to upstage patients with melanoma, the mitotic rate is defined as the number of mitoses in the dermis per mm².

"The placement of mitotic rate has substantial value for dermatologists because the question we get asked often is, ‘What is the risk of this superficial melanoma spreading to other parts of the body, either regionally to the lymph nodes or distantly to other sites?’" said Dr. Kent, a clinical instructor in the division of dermatology at the Medical College of Georgia, Augusta, who was not involved in assembling the guidelines. "With the mitotic rate less than 1 mm², it gives us a little bit more comfort in recommending to the patient that there’s less risk of spread. However, if there were to be a substantial mitotic rate, such as 2 mm², 3 mm², 4 mm², or even higher, that would lead one to consider referring the patient for evaluation for a staging and lymph node biopsy, even though the depth of the lesion is thin."

The guidelines note that there is "strong evidence" to support mitotic rate and two other histologic features as the most important characteristics of the primary tumor to predict outcome. The other features are maximum tumor (Breslow) thickness, which "is measured from the granular layer of the overlying epidermis or base of a superficial ulceration to the deepest malignant cells invading dermis to the nearest 0.1 mm, not including deeper adventitial extension," and the presence or absence of microscopic ulceration, "defined as tumor-induced full thickness loss of epidermis with subjacent dermal tumor and reactive dermal changes."

A complete physical exam is recommended by the work group and "includes looking through the scalp, looking in the mouth, and a genital exam as well," Dr. Kent said. "In our practice we refer women to their gynecologist for that, because 1% of all melanomas are genital. We also recommend that they see their medical ophthalmologist every 2 years because you can get melanomas in different areas of the eye."

Screening blood tests, including serum lactate dehydrogenase, are "insensitive for the detection of metastatic disease," the guidelines state, while the use of routine imaging studies "is limited by a very low yield and the frequent occurrence of false positive findings. Ample evidence exists that a routine chest X-ray is a cost inefficient test for the detection of metastatic disease with a consistent relatively high false positive rate." The guidelines also note that advanced imaging studies such as positron emission tomography and computed tomography have lower sensitivity, compared with sentinel lymph node biopsy (SLNB).

As for follow-up of patients with newly diagnosed cutaneous melanoma, the guidelines recommend an annual visit with a dermatologist at the least, but note that visits may range from every 3-12 months based on a patient’s history and risk factors. "The goal of follow-up is to detect any evidence of local recurrence and to detect any additional primary melanomas that may have developed," Dr. Kent said. "I have several patients that have personally had over three melanomas. One patient has had five. Some high risk patients we see every 3 or 4 months for follow-up."

Sentinel Lymph Node Biopsy and Lentigo Maligna

The work group also addressed non-surgical treatments for lentigo maligna, a topic that was not contained in the older version of the guidelines. For example, while off-label use of topical imiquimod has been proposed for lentigo maligna, "studies are limited by highly variable treatment regimens and lack of long-term follow-up with an average of approximately 18 months," the work group wrote. "Histologic verification following treatment has shown persistent disease in approximately 25% of treated patients and progression to invasive melanoma has been noted. As an adjunctive modality following surgical excision, the efficacy of topical imiquimod has not been established. High cost of treatment, an appropriate low threshold for subsequent biopsy to exclude residual or recurrent disease, and the risk of a severe inflammatory reaction should be taken into account when considering imiquimod."

SLNB is another topic contained in the guidelines for the first time. While the work group acknowledged that SLNB is "not without controversy," it described sentinel lymph node status as "the most important prognostic factor for disease-specific survival of patients with melanoma greater than 1 mm in thickness. Whether early detection of occult nodal disease provides greater regional control has not been definitively shown, but available evidence suggests a lower rate of post-operative complications in patients who underwent completion lymph node dissection for micrometastatic disease detected by SLNB, compared to those who underwent therapeutic lymph node dissection for clinically palpable disease."

The work group acknowledged that "significant gaps" exist in research related to the management of primary cutaneous melanoma, including "standardization of the interpretation of mitotic rate; placebo-controlled trials for the treatment of lentigo maligna; the use and value of dermoscopy and other imaging modalities; the clinical and prognostic significance of the use of biomarkers and mutational analysis; and the use of sentinel lymph node biopsy."

For his part, Dr. Kent predicted that major advances in the treatment of cutaneous melanoma should occur in the coming years. "Melanoma is a very unpredictable disease," he said. "Hopefully sometime in the future, we’ll have biomarkers that will assist physicians in identifying patients who are a greater risk of more aggressive disease, of spread to both regional and distant sites. That area of research is very exciting."

Dr. Kent said that he had no relevant financial disclosures.

In patients diagnosed with invasive primary cutaneous melanoma, a detailed patient history is crucial, and a thorough examination of the skin and lymph nodes should be performed to help determine the extent of clinical spread of the disease. However, for patients with melanomas of any thickness, baseline blood tests and imaging studies are not recommended because clinical research does not support their use unless suspicious signs and symptoms are present.

Those are two recommendations contained in the American Academy of Dermatology’s updated guidelines for the treatment of primary cutaneous melanoma, which were published online in the Journal of the American Academy of Dermatology. Last updated in 2001, the new guidelines focus on biopsy techniques, pathology, surgical treatment, and long-term follow-up care.

"There are many factors that must be considered when diagnosing and treating melanoma, and these new guidelines offer physicians clinically sound recommendations on how to treat melanoma patients and potentially increase their chance of survival from this deadly disease," AAD President Dr. Ronald L. Moy said in a statement.

A 15-member work group of melanoma experts convened by the AAD and chaired by Dr. Allan C. Halpern of Memorial Sloan-Kettering Cancer Center, New York, and Timothy M. Johnson of the University of Michigan and its Comprehensive Cancer Center, Ann Arbor, reviewed clinical studies and guidelines related to melanoma treatment that appeared in English-language publications between 2000 and 2010. Members of the work group used a 3-point scale to grade evidence, and then developed clinical recommendations on the best available evidence (J. Am. Acad. Dermatol. 2011 Aug. 26 doi: 10.1016/j.jaad.2011.04.031]).

The recommendations were ranked as "A" (recommendation based on consistent and good-quality patient-oriented evidence); "B" (recommendation based on inconsistent or limited-quality patient-oriented evidence); and "C" (recommendation based on consensus, opinion, case studies, or disease-oriented evidence).

The Increased Value of Mitotic Rate

According to Dr. David E. Kent, the most significant change from the 2001 guidelines relates to staging, with mitotic rate replacing Clark level of invasion as the second factor predicting melanoma survival in addition to tumor (Breslow) thickness for tumors 1 mm or smaller in thickness.

Included as a prognostic value in the 2010 American Joint Committee on Cancer staging system to upstage patients with melanoma, the mitotic rate is defined as the number of mitoses in the dermis per mm².

"The placement of mitotic rate has substantial value for dermatologists because the question we get asked often is, ‘What is the risk of this superficial melanoma spreading to other parts of the body, either regionally to the lymph nodes or distantly to other sites?’" said Dr. Kent, a clinical instructor in the division of dermatology at the Medical College of Georgia, Augusta, who was not involved in assembling the guidelines. "With the mitotic rate less than 1 mm², it gives us a little bit more comfort in recommending to the patient that there’s less risk of spread. However, if there were to be a substantial mitotic rate, such as 2 mm², 3 mm², 4 mm², or even higher, that would lead one to consider referring the patient for evaluation for a staging and lymph node biopsy, even though the depth of the lesion is thin."

The guidelines note that there is "strong evidence" to support mitotic rate and two other histologic features as the most important characteristics of the primary tumor to predict outcome. The other features are maximum tumor (Breslow) thickness, which "is measured from the granular layer of the overlying epidermis or base of a superficial ulceration to the deepest malignant cells invading dermis to the nearest 0.1 mm, not including deeper adventitial extension," and the presence or absence of microscopic ulceration, "defined as tumor-induced full thickness loss of epidermis with subjacent dermal tumor and reactive dermal changes."

A complete physical exam is recommended by the work group and "includes looking through the scalp, looking in the mouth, and a genital exam as well," Dr. Kent said. "In our practice we refer women to their gynecologist for that, because 1% of all melanomas are genital. We also recommend that they see their medical ophthalmologist every 2 years because you can get melanomas in different areas of the eye."

Screening blood tests, including serum lactate dehydrogenase, are "insensitive for the detection of metastatic disease," the guidelines state, while the use of routine imaging studies "is limited by a very low yield and the frequent occurrence of false positive findings. Ample evidence exists that a routine chest X-ray is a cost inefficient test for the detection of metastatic disease with a consistent relatively high false positive rate." The guidelines also note that advanced imaging studies such as positron emission tomography and computed tomography have lower sensitivity, compared with sentinel lymph node biopsy (SLNB).

As for follow-up of patients with newly diagnosed cutaneous melanoma, the guidelines recommend an annual visit with a dermatologist at the least, but note that visits may range from every 3-12 months based on a patient’s history and risk factors. "The goal of follow-up is to detect any evidence of local recurrence and to detect any additional primary melanomas that may have developed," Dr. Kent said. "I have several patients that have personally had over three melanomas. One patient has had five. Some high risk patients we see every 3 or 4 months for follow-up."

Sentinel Lymph Node Biopsy and Lentigo Maligna

The work group also addressed non-surgical treatments for lentigo maligna, a topic that was not contained in the older version of the guidelines. For example, while off-label use of topical imiquimod has been proposed for lentigo maligna, "studies are limited by highly variable treatment regimens and lack of long-term follow-up with an average of approximately 18 months," the work group wrote. "Histologic verification following treatment has shown persistent disease in approximately 25% of treated patients and progression to invasive melanoma has been noted. As an adjunctive modality following surgical excision, the efficacy of topical imiquimod has not been established. High cost of treatment, an appropriate low threshold for subsequent biopsy to exclude residual or recurrent disease, and the risk of a severe inflammatory reaction should be taken into account when considering imiquimod."

SLNB is another topic contained in the guidelines for the first time. While the work group acknowledged that SLNB is "not without controversy," it described sentinel lymph node status as "the most important prognostic factor for disease-specific survival of patients with melanoma greater than 1 mm in thickness. Whether early detection of occult nodal disease provides greater regional control has not been definitively shown, but available evidence suggests a lower rate of post-operative complications in patients who underwent completion lymph node dissection for micrometastatic disease detected by SLNB, compared to those who underwent therapeutic lymph node dissection for clinically palpable disease."

The work group acknowledged that "significant gaps" exist in research related to the management of primary cutaneous melanoma, including "standardization of the interpretation of mitotic rate; placebo-controlled trials for the treatment of lentigo maligna; the use and value of dermoscopy and other imaging modalities; the clinical and prognostic significance of the use of biomarkers and mutational analysis; and the use of sentinel lymph node biopsy."

For his part, Dr. Kent predicted that major advances in the treatment of cutaneous melanoma should occur in the coming years. "Melanoma is a very unpredictable disease," he said. "Hopefully sometime in the future, we’ll have biomarkers that will assist physicians in identifying patients who are a greater risk of more aggressive disease, of spread to both regional and distant sites. That area of research is very exciting."

Dr. Kent said that he had no relevant financial disclosures.

Dermatologists currently have little training in nanodermatology, but they want to learn more, according to the results of a study published this month in the Journal of Drugs in Dermatology.

The survey was conducted by Dr. Adnan Nasir and Dr. Adam Friedman, president and vice president, respectively, of the Nanodermatology Society.

They sent an online survey to members of the dermatology community including dermatology trainees, investigators, and faculty at U.S. academic medical centers (J Drugs Dermatol. 2011;10:1037-41.).

Data from 23 respondents showed that 70% had not had any type of education related to nanotechnology, despite its long-term use in sunscreens and cosmetics, and its more recent evolution into prescription skin medications (particularly acne treatments), the researchers noted.

More than three quarter of the respondents (78%) said they agreed that "nanotechnology research can contribute to better fundamental understanding of skin disease," and that nanodermatology research should be funded. However, 61% said they were uncertain regarding nanodermatology safety in pharmaceutical and cosmeceutical products.

The results of the preliminary study may help establish the groundwork for larger survey studies to better assess the need for more nanodermatology education, the researchers noted. Stay tuned for chances to learn more about the big role tiny particles play in dermatology.

-Heidi Splete (on twitter @hsplete)

Dermatologists currently have little training in nanodermatology, but they want to learn more, according to the results of a study published this month in the Journal of Drugs in Dermatology.

The survey was conducted by Dr. Adnan Nasir and Dr. Adam Friedman, president and vice president, respectively, of the Nanodermatology Society.

They sent an online survey to members of the dermatology community including dermatology trainees, investigators, and faculty at U.S. academic medical centers (J Drugs Dermatol. 2011;10:1037-41.).

Data from 23 respondents showed that 70% had not had any type of education related to nanotechnology, despite its long-term use in sunscreens and cosmetics, and its more recent evolution into prescription skin medications (particularly acne treatments), the researchers noted.

More than three quarter of the respondents (78%) said they agreed that "nanotechnology research can contribute to better fundamental understanding of skin disease," and that nanodermatology research should be funded. However, 61% said they were uncertain regarding nanodermatology safety in pharmaceutical and cosmeceutical products.

The results of the preliminary study may help establish the groundwork for larger survey studies to better assess the need for more nanodermatology education, the researchers noted. Stay tuned for chances to learn more about the big role tiny particles play in dermatology.

-Heidi Splete (on twitter @hsplete)

Dermatologists currently have little training in nanodermatology, but they want to learn more, according to the results of a study published this month in the Journal of Drugs in Dermatology.

The survey was conducted by Dr. Adnan Nasir and Dr. Adam Friedman, president and vice president, respectively, of the Nanodermatology Society.

They sent an online survey to members of the dermatology community including dermatology trainees, investigators, and faculty at U.S. academic medical centers (J Drugs Dermatol. 2011;10:1037-41.).

Data from 23 respondents showed that 70% had not had any type of education related to nanotechnology, despite its long-term use in sunscreens and cosmetics, and its more recent evolution into prescription skin medications (particularly acne treatments), the researchers noted.

More than three quarter of the respondents (78%) said they agreed that "nanotechnology research can contribute to better fundamental understanding of skin disease," and that nanodermatology research should be funded. However, 61% said they were uncertain regarding nanodermatology safety in pharmaceutical and cosmeceutical products.

The results of the preliminary study may help establish the groundwork for larger survey studies to better assess the need for more nanodermatology education, the researchers noted. Stay tuned for chances to learn more about the big role tiny particles play in dermatology.

-Heidi Splete (on twitter @hsplete)

A team of scientists from the University of Michigan reported the development of a compact, portable laser that may safely and simply treat.

The laser is said to be the size of a DVD. The chief developer is Mohammed Islam, a professor of both electrical engineering and internal medicine at the university.

Dr. Islam said that his primary interest has been fiber optics. "We're taking what we've known for years in that field and building a laser that's compact and economical and has real potential to make it to the marketplace," he said in a statement.

The device is an all fiber-based Raman laser that emits at 1,708-nanometers. It was built "using commercially available telecommunications components," Dr. Islam and his colleagues reported in the August edition of Lasers in Surgery and Medicine (2011;6:470-80).

The 1,708-nm infrared beam has a unique wavelength that is absorbed more efficiently by fat, according to Dr. Islam and his colleagues. That allows the beam to penetrate deeper into the skin (a reported 1.5 mm or more), since it will not be blocked by water.

They tested the laser on two tissue types: an ex-vivo porcine heart tissue cross-section consisting of pericardial adipose and myocardium, and an ex-vivo porcine skin tissue cross-section consisting of epidermis, dermis, and subcutaneous fat.

They also conducted histochemistry tests on human skin that had been treated by the laser. Cooling was required to prevent superficial burns; with that, they were able to achieve thermal damage to sebaceous glands at depths of up 1.65 mm into the dermis.

Dr. Jeffrey Orringer, a coahuthor and a professor of dermatology at the University, said in a statement that, "This laser system has the potential to alter sebaceous glands in the skin and thereby impact the pathogenesis of acne."

In the paper, however, he, Dr. Islam and colleagues concluded, "Selective damage of sebaceous glands was suggested but not definitively demonstrated."

Laser acne treatments exist, but have shown mixed results. Dr. Islam and his colleagues reported that lasers with wavelengths of 1,320 nm, 1,450 nm, and 1,540 nm "target the water content in the dermis and cause non-specific thermal damage including injury to sebaceous glands, but this effect on sebaceous glands was seen to be quite transient." These lasers also aren't able to penetrate very deeply, "making these wavelengths theoretically less effective at targeting sebaceous glands located deeper into the dermis."

Mr. Islam has licensed his laser technology to a University of Michigan start-up company, Omni Sciences. The research was supported by the University of Michigan Cardiovascular Center and Omni Sciences. Mr. Islam is the founder, president, and chief technology officer of Omni Sciences.

- Alicia Ault (on Twitter @aliciaault)

A team of scientists from the University of Michigan reported the development of a compact, portable laser that may safely and simply treat.

The laser is said to be the size of a DVD. The chief developer is Mohammed Islam, a professor of both electrical engineering and internal medicine at the university.

Dr. Islam said that his primary interest has been fiber optics. "We're taking what we've known for years in that field and building a laser that's compact and economical and has real potential to make it to the marketplace," he said in a statement.

The device is an all fiber-based Raman laser that emits at 1,708-nanometers. It was built "using commercially available telecommunications components," Dr. Islam and his colleagues reported in the August edition of Lasers in Surgery and Medicine (2011;6:470-80).

The 1,708-nm infrared beam has a unique wavelength that is absorbed more efficiently by fat, according to Dr. Islam and his colleagues. That allows the beam to penetrate deeper into the skin (a reported 1.5 mm or more), since it will not be blocked by water.

They tested the laser on two tissue types: an ex-vivo porcine heart tissue cross-section consisting of pericardial adipose and myocardium, and an ex-vivo porcine skin tissue cross-section consisting of epidermis, dermis, and subcutaneous fat.

They also conducted histochemistry tests on human skin that had been treated by the laser. Cooling was required to prevent superficial burns; with that, they were able to achieve thermal damage to sebaceous glands at depths of up 1.65 mm into the dermis.

Dr. Jeffrey Orringer, a coahuthor and a professor of dermatology at the University, said in a statement that, "This laser system has the potential to alter sebaceous glands in the skin and thereby impact the pathogenesis of acne."

In the paper, however, he, Dr. Islam and colleagues concluded, "Selective damage of sebaceous glands was suggested but not definitively demonstrated."

Laser acne treatments exist, but have shown mixed results. Dr. Islam and his colleagues reported that lasers with wavelengths of 1,320 nm, 1,450 nm, and 1,540 nm "target the water content in the dermis and cause non-specific thermal damage including injury to sebaceous glands, but this effect on sebaceous glands was seen to be quite transient." These lasers also aren't able to penetrate very deeply, "making these wavelengths theoretically less effective at targeting sebaceous glands located deeper into the dermis."

Mr. Islam has licensed his laser technology to a University of Michigan start-up company, Omni Sciences. The research was supported by the University of Michigan Cardiovascular Center and Omni Sciences. Mr. Islam is the founder, president, and chief technology officer of Omni Sciences.

- Alicia Ault (on Twitter @aliciaault)

A team of scientists from the University of Michigan reported the development of a compact, portable laser that may safely and simply treat.

The laser is said to be the size of a DVD. The chief developer is Mohammed Islam, a professor of both electrical engineering and internal medicine at the university.

Dr. Islam said that his primary interest has been fiber optics. "We're taking what we've known for years in that field and building a laser that's compact and economical and has real potential to make it to the marketplace," he said in a statement.

The device is an all fiber-based Raman laser that emits at 1,708-nanometers. It was built "using commercially available telecommunications components," Dr. Islam and his colleagues reported in the August edition of Lasers in Surgery and Medicine (2011;6:470-80).

The 1,708-nm infrared beam has a unique wavelength that is absorbed more efficiently by fat, according to Dr. Islam and his colleagues. That allows the beam to penetrate deeper into the skin (a reported 1.5 mm or more), since it will not be blocked by water.

They tested the laser on two tissue types: an ex-vivo porcine heart tissue cross-section consisting of pericardial adipose and myocardium, and an ex-vivo porcine skin tissue cross-section consisting of epidermis, dermis, and subcutaneous fat.

They also conducted histochemistry tests on human skin that had been treated by the laser. Cooling was required to prevent superficial burns; with that, they were able to achieve thermal damage to sebaceous glands at depths of up 1.65 mm into the dermis.

Dr. Jeffrey Orringer, a coahuthor and a professor of dermatology at the University, said in a statement that, "This laser system has the potential to alter sebaceous glands in the skin and thereby impact the pathogenesis of acne."

In the paper, however, he, Dr. Islam and colleagues concluded, "Selective damage of sebaceous glands was suggested but not definitively demonstrated."

Laser acne treatments exist, but have shown mixed results. Dr. Islam and his colleagues reported that lasers with wavelengths of 1,320 nm, 1,450 nm, and 1,540 nm "target the water content in the dermis and cause non-specific thermal damage including injury to sebaceous glands, but this effect on sebaceous glands was seen to be quite transient." These lasers also aren't able to penetrate very deeply, "making these wavelengths theoretically less effective at targeting sebaceous glands located deeper into the dermis."

Mr. Islam has licensed his laser technology to a University of Michigan start-up company, Omni Sciences. The research was supported by the University of Michigan Cardiovascular Center and Omni Sciences. Mr. Islam is the founder, president, and chief technology officer of Omni Sciences.

- Alicia Ault (on Twitter @aliciaault)

NEW YORK – Sentinel lymph node biopsy continues to aid the management of about 30% of melanoma patients, though its role in the future will depend on ongoing follow-up of a major trial that started nearly 20 years ago to assess the effect of SLNB on patient survival.

But SLNB’s role could soon be upstaged by molecular profiling and the identification of specific genetic mutations that drive various melanoma subtypes, Dr. Timothy M. Johnson said at the American Academy of Dermatology’s Summer Academy Meeting.

"In the future, I hope we can do molecular profiling on melanoma and [based on that] tell patients who will benefit [from various targeted treatments] and who won’t. We are already doing this [on an investigational basis] with several new molecular profiling tests such as BRAF mutations" and treatment with vemurafenib, said Dr. Johnson, a professor of dermatology at the University of Michigan in Ann Arbor.

For the time being, melanoma patients should be counseled regarding SLNB if their tumors are at least 0.75 mm in Breslow depth and if they meet certain other criteria.

Even patients with thinner tumors should be counseled on the pros and cons of SLNB, because they will likely hear or know about the technique and may have questions. That is the approach taken at the University of Michigan and other centers, he said.

"SLN status is a powerful predictor of survival in the relatively small subset of patients where SLNB is indicated," he said. Reasons not to do SLNB include thin primary melanomas generally less than 0.75 mm with a low probability of a positive SLNB, high comorbidities, and maybe prior wide local excision, certainly in areas of ambiguous lymphatic drainage or following a local flap. This group includes about 70% of all U.S. melanoma patients. Albeit rarely, these thin lesions may be at higher risk when they have greater degrees of adverse features or positive deep margins on shave biopsy.

Melanoma patients with primary tumors that are 0.75-0.99 mm generally need an additional risk factor, such as ulceration, young age – up to about 40 years old, an increased mitotic rate, or angiolymphatic invasion to justify SLNB. When patients have additional risk factors, "we have a discussion with the patient to help them decide," he said. "We tell them the likely rate of positive lymph nodes based on our best information."

A clearer role for SLNB exists for patients with tumors with a Breslow thickness of 1 mm or greater. In these patients, exclusions from SLNB include "highly significant" medical comorbidities, a prior wide excision of the tumor, and tumors in "ambiguous" lymphatic drainage areas, such as the central back or central chest. Even in these cases, exclusion from SLNB "usually occurs but not always," Dr. Johnson noted.

Patients whose tumors have a Breslow thickness of more than 4 mm are also candidates for SLNB. In these cases, SLNB can help refine the patient’s prognosis, and may also aid the choice of adjuvant therapy.

Historically, patients with tumors 4 mm or larger were considered likely to have distant metastatic disease and a poor prognosis, and, hence, no benefit from SLNB. But Dr. Johnson and his colleagues showed a substantial difference in survival rate between patients with positive and negative SLNs even when they had thicker primary tumors.

In a series of 227 patients with melanomas at least 4 mm thick and no clinically or radiologically-apparent distant disease, patients with a positive SLNB had a 5-year overall survival rate of 47%, while patients with negative SLNs had a 5-year survival rate of 80%, a statistically significant difference (P less than .0001). The difference in 5-year distant disease-free survival rates ran slightly larger, 85% in the node-negative patients and 48% in the node-positive patients (P less than .0001) (Cancer 2009;115:5752-60). Following this study, supporting evidence has come from several other research groups.

The ongoing Multicenter Selective Lymphadenectomy Trial (MSLT) should provide more definitive evidence on the survival effects of SLNB. The interim, 5-year follow-up data from 1,327 patients at 18 worldwide centers reported in 2006 included patients with primary-tumor Breslow thicknesses of 1.2-3.5 mm. Although the study’s primary endpoint of the 5-year melanoma-specific survival rate was similar in the patients randomized to SLNB or wide local excision (87%), the prespecified secondary endpoint of 5-year disease-free survival ran 78% in patients who underwent SLNB and 73% in the wide excision group, a statistically-significant difference (P = .009) (N. Engl. J. Med. 2006;355:1307-17).

"The question is, can we identify a subset of patients with occult nodal disease with SLNB, intervene early, and improve outcomes? At face value, the third interim analysis data [the 2006 report] suggests potentially yes. However, this is a subset analysis and its validity can be debated. The data certainly support the potential for a subset benefit in node-positive patients," said Dr. Johnson. Updated survival results from a longer-term, fourth interim analysis of the MSLT survival outcomes are expected within the next year, and will help answer this question.

In addition to the disease-free survival benefit shown in the MSLT, the 30% of melanoma patients who are candidates for SLNB stand to gain useful prognostic information from the procedure. On average, about 20% of patients who are eligible for SLNB have a positive SLN, and this subgroup of patients also stand to benefit from more durable regional control of their disease with better quality of life. The survival benefit most likely occurs in a subset, perhaps 20%, of the node-positive patients, he said.

In summary, Dr. Johnson said the main reasons to consider SLNB are prognosis, durable regional control, and potential survival benefit in a select subset. These factors should be presented in "an honest discussion with the patient and family about the risks and benefits of SLNB, to help them make a best informed decision," he said.

Although many cancer centers currently use SLNB for melanoma in the way outlined by Dr. Johnson, with "not much controversy" among the "mainstream" of physicians and surgeons who treat melanoma, he noted that "there is posturing and emotion with this procedure," with controversy among some clinicians about the proper role.

"Some dermatologists don’t believe that SLNB should be used for anybody, and some surgeons overuse it on everybody. The answer [on when to use SLNB] is somewhere in between," he said in an interview. The forthcoming, longer-term follow-up data from MSLT may help clinicians how best to use SLNB most appropriately, he added.

Dr. Johnson said that he had no disclosures.

NEW YORK – Sentinel lymph node biopsy continues to aid the management of about 30% of melanoma patients, though its role in the future will depend on ongoing follow-up of a major trial that started nearly 20 years ago to assess the effect of SLNB on patient survival.

But SLNB’s role could soon be upstaged by molecular profiling and the identification of specific genetic mutations that drive various melanoma subtypes, Dr. Timothy M. Johnson said at the American Academy of Dermatology’s Summer Academy Meeting.

"In the future, I hope we can do molecular profiling on melanoma and [based on that] tell patients who will benefit [from various targeted treatments] and who won’t. We are already doing this [on an investigational basis] with several new molecular profiling tests such as BRAF mutations" and treatment with vemurafenib, said Dr. Johnson, a professor of dermatology at the University of Michigan in Ann Arbor.

For the time being, melanoma patients should be counseled regarding SLNB if their tumors are at least 0.75 mm in Breslow depth and if they meet certain other criteria.

Even patients with thinner tumors should be counseled on the pros and cons of SLNB, because they will likely hear or know about the technique and may have questions. That is the approach taken at the University of Michigan and other centers, he said.

"SLN status is a powerful predictor of survival in the relatively small subset of patients where SLNB is indicated," he said. Reasons not to do SLNB include thin primary melanomas generally less than 0.75 mm with a low probability of a positive SLNB, high comorbidities, and maybe prior wide local excision, certainly in areas of ambiguous lymphatic drainage or following a local flap. This group includes about 70% of all U.S. melanoma patients. Albeit rarely, these thin lesions may be at higher risk when they have greater degrees of adverse features or positive deep margins on shave biopsy.

Melanoma patients with primary tumors that are 0.75-0.99 mm generally need an additional risk factor, such as ulceration, young age – up to about 40 years old, an increased mitotic rate, or angiolymphatic invasion to justify SLNB. When patients have additional risk factors, "we have a discussion with the patient to help them decide," he said. "We tell them the likely rate of positive lymph nodes based on our best information."

A clearer role for SLNB exists for patients with tumors with a Breslow thickness of 1 mm or greater. In these patients, exclusions from SLNB include "highly significant" medical comorbidities, a prior wide excision of the tumor, and tumors in "ambiguous" lymphatic drainage areas, such as the central back or central chest. Even in these cases, exclusion from SLNB "usually occurs but not always," Dr. Johnson noted.

Patients whose tumors have a Breslow thickness of more than 4 mm are also candidates for SLNB. In these cases, SLNB can help refine the patient’s prognosis, and may also aid the choice of adjuvant therapy.

Historically, patients with tumors 4 mm or larger were considered likely to have distant metastatic disease and a poor prognosis, and, hence, no benefit from SLNB. But Dr. Johnson and his colleagues showed a substantial difference in survival rate between patients with positive and negative SLNs even when they had thicker primary tumors.

In a series of 227 patients with melanomas at least 4 mm thick and no clinically or radiologically-apparent distant disease, patients with a positive SLNB had a 5-year overall survival rate of 47%, while patients with negative SLNs had a 5-year survival rate of 80%, a statistically significant difference (P less than .0001). The difference in 5-year distant disease-free survival rates ran slightly larger, 85% in the node-negative patients and 48% in the node-positive patients (P less than .0001) (Cancer 2009;115:5752-60). Following this study, supporting evidence has come from several other research groups.

The ongoing Multicenter Selective Lymphadenectomy Trial (MSLT) should provide more definitive evidence on the survival effects of SLNB. The interim, 5-year follow-up data from 1,327 patients at 18 worldwide centers reported in 2006 included patients with primary-tumor Breslow thicknesses of 1.2-3.5 mm. Although the study’s primary endpoint of the 5-year melanoma-specific survival rate was similar in the patients randomized to SLNB or wide local excision (87%), the prespecified secondary endpoint of 5-year disease-free survival ran 78% in patients who underwent SLNB and 73% in the wide excision group, a statistically-significant difference (P = .009) (N. Engl. J. Med. 2006;355:1307-17).

"The question is, can we identify a subset of patients with occult nodal disease with SLNB, intervene early, and improve outcomes? At face value, the third interim analysis data [the 2006 report] suggests potentially yes. However, this is a subset analysis and its validity can be debated. The data certainly support the potential for a subset benefit in node-positive patients," said Dr. Johnson. Updated survival results from a longer-term, fourth interim analysis of the MSLT survival outcomes are expected within the next year, and will help answer this question.

In addition to the disease-free survival benefit shown in the MSLT, the 30% of melanoma patients who are candidates for SLNB stand to gain useful prognostic information from the procedure. On average, about 20% of patients who are eligible for SLNB have a positive SLN, and this subgroup of patients also stand to benefit from more durable regional control of their disease with better quality of life. The survival benefit most likely occurs in a subset, perhaps 20%, of the node-positive patients, he said.

In summary, Dr. Johnson said the main reasons to consider SLNB are prognosis, durable regional control, and potential survival benefit in a select subset. These factors should be presented in "an honest discussion with the patient and family about the risks and benefits of SLNB, to help them make a best informed decision," he said.

Although many cancer centers currently use SLNB for melanoma in the way outlined by Dr. Johnson, with "not much controversy" among the "mainstream" of physicians and surgeons who treat melanoma, he noted that "there is posturing and emotion with this procedure," with controversy among some clinicians about the proper role.

"Some dermatologists don’t believe that SLNB should be used for anybody, and some surgeons overuse it on everybody. The answer [on when to use SLNB] is somewhere in between," he said in an interview. The forthcoming, longer-term follow-up data from MSLT may help clinicians how best to use SLNB most appropriately, he added.

Dr. Johnson said that he had no disclosures.

NEW YORK – Sentinel lymph node biopsy continues to aid the management of about 30% of melanoma patients, though its role in the future will depend on ongoing follow-up of a major trial that started nearly 20 years ago to assess the effect of SLNB on patient survival.

But SLNB’s role could soon be upstaged by molecular profiling and the identification of specific genetic mutations that drive various melanoma subtypes, Dr. Timothy M. Johnson said at the American Academy of Dermatology’s Summer Academy Meeting.

"In the future, I hope we can do molecular profiling on melanoma and [based on that] tell patients who will benefit [from various targeted treatments] and who won’t. We are already doing this [on an investigational basis] with several new molecular profiling tests such as BRAF mutations" and treatment with vemurafenib, said Dr. Johnson, a professor of dermatology at the University of Michigan in Ann Arbor.

For the time being, melanoma patients should be counseled regarding SLNB if their tumors are at least 0.75 mm in Breslow depth and if they meet certain other criteria.

Even patients with thinner tumors should be counseled on the pros and cons of SLNB, because they will likely hear or know about the technique and may have questions. That is the approach taken at the University of Michigan and other centers, he said.

"SLN status is a powerful predictor of survival in the relatively small subset of patients where SLNB is indicated," he said. Reasons not to do SLNB include thin primary melanomas generally less than 0.75 mm with a low probability of a positive SLNB, high comorbidities, and maybe prior wide local excision, certainly in areas of ambiguous lymphatic drainage or following a local flap. This group includes about 70% of all U.S. melanoma patients. Albeit rarely, these thin lesions may be at higher risk when they have greater degrees of adverse features or positive deep margins on shave biopsy.

Melanoma patients with primary tumors that are 0.75-0.99 mm generally need an additional risk factor, such as ulceration, young age – up to about 40 years old, an increased mitotic rate, or angiolymphatic invasion to justify SLNB. When patients have additional risk factors, "we have a discussion with the patient to help them decide," he said. "We tell them the likely rate of positive lymph nodes based on our best information."

A clearer role for SLNB exists for patients with tumors with a Breslow thickness of 1 mm or greater. In these patients, exclusions from SLNB include "highly significant" medical comorbidities, a prior wide excision of the tumor, and tumors in "ambiguous" lymphatic drainage areas, such as the central back or central chest. Even in these cases, exclusion from SLNB "usually occurs but not always," Dr. Johnson noted.

Patients whose tumors have a Breslow thickness of more than 4 mm are also candidates for SLNB. In these cases, SLNB can help refine the patient’s prognosis, and may also aid the choice of adjuvant therapy.

Historically, patients with tumors 4 mm or larger were considered likely to have distant metastatic disease and a poor prognosis, and, hence, no benefit from SLNB. But Dr. Johnson and his colleagues showed a substantial difference in survival rate between patients with positive and negative SLNs even when they had thicker primary tumors.

In a series of 227 patients with melanomas at least 4 mm thick and no clinically or radiologically-apparent distant disease, patients with a positive SLNB had a 5-year overall survival rate of 47%, while patients with negative SLNs had a 5-year survival rate of 80%, a statistically significant difference (P less than .0001). The difference in 5-year distant disease-free survival rates ran slightly larger, 85% in the node-negative patients and 48% in the node-positive patients (P less than .0001) (Cancer 2009;115:5752-60). Following this study, supporting evidence has come from several other research groups.

The ongoing Multicenter Selective Lymphadenectomy Trial (MSLT) should provide more definitive evidence on the survival effects of SLNB. The interim, 5-year follow-up data from 1,327 patients at 18 worldwide centers reported in 2006 included patients with primary-tumor Breslow thicknesses of 1.2-3.5 mm. Although the study’s primary endpoint of the 5-year melanoma-specific survival rate was similar in the patients randomized to SLNB or wide local excision (87%), the prespecified secondary endpoint of 5-year disease-free survival ran 78% in patients who underwent SLNB and 73% in the wide excision group, a statistically-significant difference (P = .009) (N. Engl. J. Med. 2006;355:1307-17).

"The question is, can we identify a subset of patients with occult nodal disease with SLNB, intervene early, and improve outcomes? At face value, the third interim analysis data [the 2006 report] suggests potentially yes. However, this is a subset analysis and its validity can be debated. The data certainly support the potential for a subset benefit in node-positive patients," said Dr. Johnson. Updated survival results from a longer-term, fourth interim analysis of the MSLT survival outcomes are expected within the next year, and will help answer this question.

In addition to the disease-free survival benefit shown in the MSLT, the 30% of melanoma patients who are candidates for SLNB stand to gain useful prognostic information from the procedure. On average, about 20% of patients who are eligible for SLNB have a positive SLN, and this subgroup of patients also stand to benefit from more durable regional control of their disease with better quality of life. The survival benefit most likely occurs in a subset, perhaps 20%, of the node-positive patients, he said.

In summary, Dr. Johnson said the main reasons to consider SLNB are prognosis, durable regional control, and potential survival benefit in a select subset. These factors should be presented in "an honest discussion with the patient and family about the risks and benefits of SLNB, to help them make a best informed decision," he said.

Although many cancer centers currently use SLNB for melanoma in the way outlined by Dr. Johnson, with "not much controversy" among the "mainstream" of physicians and surgeons who treat melanoma, he noted that "there is posturing and emotion with this procedure," with controversy among some clinicians about the proper role.

"Some dermatologists don’t believe that SLNB should be used for anybody, and some surgeons overuse it on everybody. The answer [on when to use SLNB] is somewhere in between," he said in an interview. The forthcoming, longer-term follow-up data from MSLT may help clinicians how best to use SLNB most appropriately, he added.

Dr. Johnson said that he had no disclosures.

In this month's Skinny Podcast, we catch up with Dr. Richard Carvajal for the latest on the FDA's recent approval of vemurafenib for advanced-stage melanoma.

We also talk to Dr. Henry Lim about why the thinks adults and children (starting at age 1) should be taking regular vitamin D supplements.

Dr. Ronald Rapini discusses the northward march of the fire ant. His stories are sure to make your skin crawl.

In this month's Cosmetic Counter segment, Dr. Lily Talakoub lays out the facts about cleansers and offers tips that you can share with your patients.

And last but not least, Dr. Alan Rockoff entertains us with a story about a bath tub and an angry mother-in-law.

In this month's Skinny Podcast, we catch up with Dr. Richard Carvajal for the latest on the FDA's recent approval of vemurafenib for advanced-stage melanoma.

We also talk to Dr. Henry Lim about why the thinks adults and children (starting at age 1) should be taking regular vitamin D supplements.

Dr. Ronald Rapini discusses the northward march of the fire ant. His stories are sure to make your skin crawl.

In this month's Cosmetic Counter segment, Dr. Lily Talakoub lays out the facts about cleansers and offers tips that you can share with your patients.

And last but not least, Dr. Alan Rockoff entertains us with a story about a bath tub and an angry mother-in-law.

In this month's Skinny Podcast, we catch up with Dr. Richard Carvajal for the latest on the FDA's recent approval of vemurafenib for advanced-stage melanoma.

We also talk to Dr. Henry Lim about why the thinks adults and children (starting at age 1) should be taking regular vitamin D supplements.

Dr. Ronald Rapini discusses the northward march of the fire ant. His stories are sure to make your skin crawl.

In this month's Cosmetic Counter segment, Dr. Lily Talakoub lays out the facts about cleansers and offers tips that you can share with your patients.

And last but not least, Dr. Alan Rockoff entertains us with a story about a bath tub and an angry mother-in-law.

Fredric S. Brandt, MD, Alex Cazzaniga, MBA, and Michael Hann, MSc

The desire to maintain a youthful image combined with an emerging global market with disposable income has driven the development of many new industries. The cosmeceutical industry is based on the development and marketing of products that lie between cosmetics and pharmaceuticals. Today, there are over 400 suppliers and manufacturers of cosmeceutical products, and the industry is estimated to grow by 7.4% by 2012. Although a number of products advertise predictable outcomes, the industry is largely unregulated and any consumers of cosmeceutical products should consult a dermatologist prior to use. This review will provide a snapshot of the current trends of this industry and provide an analysis of this multi-billion dollar market.

*For a PDF of the full article, click on the link to the left of this introduction.

Fredric S. Brandt, MD, Alex Cazzaniga, MBA, and Michael Hann, MSc

The desire to maintain a youthful image combined with an emerging global market with disposable income has driven the development of many new industries. The cosmeceutical industry is based on the development and marketing of products that lie between cosmetics and pharmaceuticals. Today, there are over 400 suppliers and manufacturers of cosmeceutical products, and the industry is estimated to grow by 7.4% by 2012. Although a number of products advertise predictable outcomes, the industry is largely unregulated and any consumers of cosmeceutical products should consult a dermatologist prior to use. This review will provide a snapshot of the current trends of this industry and provide an analysis of this multi-billion dollar market.

*For a PDF of the full article, click on the link to the left of this introduction.

Fredric S. Brandt, MD, Alex Cazzaniga, MBA, and Michael Hann, MSc

The desire to maintain a youthful image combined with an emerging global market with disposable income has driven the development of many new industries. The cosmeceutical industry is based on the development and marketing of products that lie between cosmetics and pharmaceuticals. Today, there are over 400 suppliers and manufacturers of cosmeceutical products, and the industry is estimated to grow by 7.4% by 2012. Although a number of products advertise predictable outcomes, the industry is largely unregulated and any consumers of cosmeceutical products should consult a dermatologist prior to use. This review will provide a snapshot of the current trends of this industry and provide an analysis of this multi-billion dollar market.

*For a PDF of the full article, click on the link to the left of this introduction.

Jason Emer, MD, Heidi Waldorf, MD, and Diane Berson, MD

Rosacea is a chronic inflammatory skin condition characterized by cutaneous hypersensitivity. There are many therapeutic options available for the treatment of rosacea, but none are curative. Since the pathogenesis of rosacea remains elusive, it is not surprising that no single treatment is paramount and that many patients find therapies unsatisfactory or even exacerbating. Treatments are prescribed to work in concert with each other in order to ameliorate the common clinical manifestations, which include: papules and pustules, telangiectasias, erythema, gland hypertrophy, and ocular disease. The most validated topical therapies include metronidazole, azelaic acid, and sodium sulfacetamide-sulfur. Many other topical therapies, such as calcineurin inhibitors, benzoyl peroxide, clindamycin, retinoids, topical corticosteroids, and permethrin have demonstrated varying degrees of success. Due to the inconsistent results of the aforementioned therapies patients are increasingly turning to alternative products containing natural ingredients or botanicals to ease inflammation and remit disease. Additional research is needed to elucidate the benefits of these ingredients in the management of rosacea, but some important considerations regarding the natural ingredients with clinical data will be discussed here.

*For a PDF of the full article, click on the link to the left of this introduction.

Jason Emer, MD, Heidi Waldorf, MD, and Diane Berson, MD

Rosacea is a chronic inflammatory skin condition characterized by cutaneous hypersensitivity. There are many therapeutic options available for the treatment of rosacea, but none are curative. Since the pathogenesis of rosacea remains elusive, it is not surprising that no single treatment is paramount and that many patients find therapies unsatisfactory or even exacerbating. Treatments are prescribed to work in concert with each other in order to ameliorate the common clinical manifestations, which include: papules and pustules, telangiectasias, erythema, gland hypertrophy, and ocular disease. The most validated topical therapies include metronidazole, azelaic acid, and sodium sulfacetamide-sulfur. Many other topical therapies, such as calcineurin inhibitors, benzoyl peroxide, clindamycin, retinoids, topical corticosteroids, and permethrin have demonstrated varying degrees of success. Due to the inconsistent results of the aforementioned therapies patients are increasingly turning to alternative products containing natural ingredients or botanicals to ease inflammation and remit disease. Additional research is needed to elucidate the benefits of these ingredients in the management of rosacea, but some important considerations regarding the natural ingredients with clinical data will be discussed here.

*For a PDF of the full article, click on the link to the left of this introduction.

Jason Emer, MD, Heidi Waldorf, MD, and Diane Berson, MD

Rosacea is a chronic inflammatory skin condition characterized by cutaneous hypersensitivity. There are many therapeutic options available for the treatment of rosacea, but none are curative. Since the pathogenesis of rosacea remains elusive, it is not surprising that no single treatment is paramount and that many patients find therapies unsatisfactory or even exacerbating. Treatments are prescribed to work in concert with each other in order to ameliorate the common clinical manifestations, which include: papules and pustules, telangiectasias, erythema, gland hypertrophy, and ocular disease. The most validated topical therapies include metronidazole, azelaic acid, and sodium sulfacetamide-sulfur. Many other topical therapies, such as calcineurin inhibitors, benzoyl peroxide, clindamycin, retinoids, topical corticosteroids, and permethrin have demonstrated varying degrees of success. Due to the inconsistent results of the aforementioned therapies patients are increasingly turning to alternative products containing natural ingredients or botanicals to ease inflammation and remit disease. Additional research is needed to elucidate the benefits of these ingredients in the management of rosacea, but some important considerations regarding the natural ingredients with clinical data will be discussed here.

*For a PDF of the full article, click on the link to the left of this introduction.

Mary Lupo, MD, and Leah Jacob, MD

The use of laser resurfacing for cutaneous rejuvenation has become an important tool in the modern dermatologist’s armamentarium. To ensure a successful outcome, proper preoperative and postoperative skin care is essential. Incorporating cosmeceuticals into the perioperative skin care regimen can promote a better overall patient experience by hastening postoperative healing, reducing common side effects, and enhancing overall rejuvenation. This article aims to explore the use of various cosmeceuticals in conjunction with laser resurfacing procedures. In particular, the overall mechanisms of action behind each selected therapy will be discussed, followed by a brief discussion of the existing literature on each agent’s use with laser resurfacing. Theoretical considerations and a limited body of evidence suggest a potential benefit for the use of these agents in conjunction with laser resurfacing procedures; however, further placebo-controlled studies are needed to truly confirm these benefits.

*For a PDF of the full article, click on the link to the left of this introduction.

Mary Lupo, MD, and Leah Jacob, MD

The use of laser resurfacing for cutaneous rejuvenation has become an important tool in the modern dermatologist’s armamentarium. To ensure a successful outcome, proper preoperative and postoperative skin care is essential. Incorporating cosmeceuticals into the perioperative skin care regimen can promote a better overall patient experience by hastening postoperative healing, reducing common side effects, and enhancing overall rejuvenation. This article aims to explore the use of various cosmeceuticals in conjunction with laser resurfacing procedures. In particular, the overall mechanisms of action behind each selected therapy will be discussed, followed by a brief discussion of the existing literature on each agent’s use with laser resurfacing. Theoretical considerations and a limited body of evidence suggest a potential benefit for the use of these agents in conjunction with laser resurfacing procedures; however, further placebo-controlled studies are needed to truly confirm these benefits.

*For a PDF of the full article, click on the link to the left of this introduction.

Mary Lupo, MD, and Leah Jacob, MD

The use of laser resurfacing for cutaneous rejuvenation has become an important tool in the modern dermatologist’s armamentarium. To ensure a successful outcome, proper preoperative and postoperative skin care is essential. Incorporating cosmeceuticals into the perioperative skin care regimen can promote a better overall patient experience by hastening postoperative healing, reducing common side effects, and enhancing overall rejuvenation. This article aims to explore the use of various cosmeceuticals in conjunction with laser resurfacing procedures. In particular, the overall mechanisms of action behind each selected therapy will be discussed, followed by a brief discussion of the existing literature on each agent’s use with laser resurfacing. Theoretical considerations and a limited body of evidence suggest a potential benefit for the use of these agents in conjunction with laser resurfacing procedures; however, further placebo-controlled studies are needed to truly confirm these benefits.

*For a PDF of the full article, click on the link to the left of this introduction.