Melanoma

SAN DIEGO — Confocal microscopy is a promising technology to improve the management of skin lesions, but it's not quite ready for prime time, according to Dr. Lawrence T. Wang.

"At this time, the technology is very expensive, costing several tens of thousand of dollars," said Dr. Wang of the division of dermatology at Scripps Clinic Rancho Bernardo in San Diego, Calif. "It is time consuming, requiring 5-10 minutes to thoroughly evaluate a single lesion. The process is labor intensive and would likely require a trained clinician to interpret the images."

Confocal microscopy is a high-resolution, painless imaging technique that reveals epidermal structures including cells, connective tissue, and blood vessels to a maximum depth of about 300 microns. The illumination source is typically a laser.

"Only one point in the tissue is acquired at a time, so two-dimensional or even three-dimensional images are generated by scanning the tissue," Dr. Wang said at a melanoma update sponsored by the Scripps Clinic.

Findings from two recent studies suggest confocal microscopy may be useful in helping to improve the diagnosis of melanoma in the clinical setting. In one study, researchers from Italy and Australia evaluated 351 melanocytic lesions that were suspicious for melanoma based on clinical history, sequential digital photography, or dermoscopy (J. Invest. Dermatol. 2007;127:2759-65). They evaluated each lesion with confocal microscopy prior to biopsy and classified the lesions as either benign or malignant according to an algorithm based on major and minor criteria. They found that confocal microscopy showed a sensitivity of 96% and a specificity of 52%.

In the second study, Canadian researchers evaluated 125 suspicious pigmented lesions by dermoscopy followed by confocal microscopy (Dermatology 2007;215:365-72). The lesions were selected based on a history of change or clinical appearance. They found that confocal microscopy showed a sensitivity of 97% and specificity of 83%. The higher specificity "is likely due to the study design," Dr. Wang commented. "The authors' dermoscopic evaluation influenced their subsequent confocal evaluation. The study was designed this way to mimic a realistic clinical application of confocal microscopy."

Larger clinical trials of the technology are currently under way.
In Dr. Wang's opinion, current benefits of confocal microscopy include the fact that it provides immediate, real time, in vivo images prior to biopsy, removing the need for tissue preservation, sectioning, or staining. "This type of technology can significantly minimize sampling error when incisional biopsies are done of large pigmented lesions," he said. "The images are microscopic, giving single cell resolution."

However, the in vivo imaging falls short of conventional histology, he said, noting that nuclear features such as chromatin patterns, nuclear contours, and nucleoli "cannot be evaluated by confocal microscopy."

He also pointed out that since the depth of confocal microscopy is limited to the reticular dermis, subsequent biopsy of suspicious lesions "will always be needed to obtain a Breslow depth for melanoma lesions."

At this point in time, one of the best clinical applications of the technology is for managing large, atypical pigmented lesions. "Lesions in cosmetically sensitive areas such as the face are prone to sampling errors when partial biopsies are done," Dr. Wang explained. "Confocal microscopy could be used to scan entire lesions and direct appropriate sampling biopsies."

Dr. Wang disclosed having no relevant conflicts of interest.

SAN DIEGO — Confocal microscopy is a promising technology to improve the management of skin lesions, but it's not quite ready for prime time, according to Dr. Lawrence T. Wang.

"At this time, the technology is very expensive, costing several tens of thousand of dollars," said Dr. Wang of the division of dermatology at Scripps Clinic Rancho Bernardo in San Diego, Calif. "It is time consuming, requiring 5-10 minutes to thoroughly evaluate a single lesion. The process is labor intensive and would likely require a trained clinician to interpret the images."

Confocal microscopy is a high-resolution, painless imaging technique that reveals epidermal structures including cells, connective tissue, and blood vessels to a maximum depth of about 300 microns. The illumination source is typically a laser.

"Only one point in the tissue is acquired at a time, so two-dimensional or even three-dimensional images are generated by scanning the tissue," Dr. Wang said at a melanoma update sponsored by the Scripps Clinic.

Findings from two recent studies suggest confocal microscopy may be useful in helping to improve the diagnosis of melanoma in the clinical setting. In one study, researchers from Italy and Australia evaluated 351 melanocytic lesions that were suspicious for melanoma based on clinical history, sequential digital photography, or dermoscopy (J. Invest. Dermatol. 2007;127:2759-65). They evaluated each lesion with confocal microscopy prior to biopsy and classified the lesions as either benign or malignant according to an algorithm based on major and minor criteria. They found that confocal microscopy showed a sensitivity of 96% and a specificity of 52%.

In the second study, Canadian researchers evaluated 125 suspicious pigmented lesions by dermoscopy followed by confocal microscopy (Dermatology 2007;215:365-72). The lesions were selected based on a history of change or clinical appearance. They found that confocal microscopy showed a sensitivity of 97% and specificity of 83%. The higher specificity "is likely due to the study design," Dr. Wang commented. "The authors' dermoscopic evaluation influenced their subsequent confocal evaluation. The study was designed this way to mimic a realistic clinical application of confocal microscopy."

Larger clinical trials of the technology are currently under way.
In Dr. Wang's opinion, current benefits of confocal microscopy include the fact that it provides immediate, real time, in vivo images prior to biopsy, removing the need for tissue preservation, sectioning, or staining. "This type of technology can significantly minimize sampling error when incisional biopsies are done of large pigmented lesions," he said. "The images are microscopic, giving single cell resolution."

However, the in vivo imaging falls short of conventional histology, he said, noting that nuclear features such as chromatin patterns, nuclear contours, and nucleoli "cannot be evaluated by confocal microscopy."

He also pointed out that since the depth of confocal microscopy is limited to the reticular dermis, subsequent biopsy of suspicious lesions "will always be needed to obtain a Breslow depth for melanoma lesions."

At this point in time, one of the best clinical applications of the technology is for managing large, atypical pigmented lesions. "Lesions in cosmetically sensitive areas such as the face are prone to sampling errors when partial biopsies are done," Dr. Wang explained. "Confocal microscopy could be used to scan entire lesions and direct appropriate sampling biopsies."

Dr. Wang disclosed having no relevant conflicts of interest.

SAN DIEGO — Confocal microscopy is a promising technology to improve the management of skin lesions, but it's not quite ready for prime time, according to Dr. Lawrence T. Wang.

"At this time, the technology is very expensive, costing several tens of thousand of dollars," said Dr. Wang of the division of dermatology at Scripps Clinic Rancho Bernardo in San Diego, Calif. "It is time consuming, requiring 5-10 minutes to thoroughly evaluate a single lesion. The process is labor intensive and would likely require a trained clinician to interpret the images."

Confocal microscopy is a high-resolution, painless imaging technique that reveals epidermal structures including cells, connective tissue, and blood vessels to a maximum depth of about 300 microns. The illumination source is typically a laser.

"Only one point in the tissue is acquired at a time, so two-dimensional or even three-dimensional images are generated by scanning the tissue," Dr. Wang said at a melanoma update sponsored by the Scripps Clinic.

Findings from two recent studies suggest confocal microscopy may be useful in helping to improve the diagnosis of melanoma in the clinical setting. In one study, researchers from Italy and Australia evaluated 351 melanocytic lesions that were suspicious for melanoma based on clinical history, sequential digital photography, or dermoscopy (J. Invest. Dermatol. 2007;127:2759-65). They evaluated each lesion with confocal microscopy prior to biopsy and classified the lesions as either benign or malignant according to an algorithm based on major and minor criteria. They found that confocal microscopy showed a sensitivity of 96% and a specificity of 52%.

In the second study, Canadian researchers evaluated 125 suspicious pigmented lesions by dermoscopy followed by confocal microscopy (Dermatology 2007;215:365-72). The lesions were selected based on a history of change or clinical appearance. They found that confocal microscopy showed a sensitivity of 97% and specificity of 83%. The higher specificity "is likely due to the study design," Dr. Wang commented. "The authors' dermoscopic evaluation influenced their subsequent confocal evaluation. The study was designed this way to mimic a realistic clinical application of confocal microscopy."

Larger clinical trials of the technology are currently under way.
In Dr. Wang's opinion, current benefits of confocal microscopy include the fact that it provides immediate, real time, in vivo images prior to biopsy, removing the need for tissue preservation, sectioning, or staining. "This type of technology can significantly minimize sampling error when incisional biopsies are done of large pigmented lesions," he said. "The images are microscopic, giving single cell resolution."

However, the in vivo imaging falls short of conventional histology, he said, noting that nuclear features such as chromatin patterns, nuclear contours, and nucleoli "cannot be evaluated by confocal microscopy."

He also pointed out that since the depth of confocal microscopy is limited to the reticular dermis, subsequent biopsy of suspicious lesions "will always be needed to obtain a Breslow depth for melanoma lesions."

At this point in time, one of the best clinical applications of the technology is for managing large, atypical pigmented lesions. "Lesions in cosmetically sensitive areas such as the face are prone to sampling errors when partial biopsies are done," Dr. Wang explained. "Confocal microscopy could be used to scan entire lesions and direct appropriate sampling biopsies."

Dr. Wang disclosed having no relevant conflicts of interest.

The Indoor Tanning Association (ITA) is really feeling the heat these days.

The Food and Drug Administration (FDA) said it would finally act on congressional orders to take a closer look at tanning bed labels (see my earlier post), and now the Federal Trade Commission (FTC) said it has exacted a settlement from the ITA to cease and desist "false health and safety claims about indoor tanning."

The FTC said, "Contrary to claims in the association’s advertising, indoor tanning increases the risk of squamous cell and melanoma skin cancers."

The agency’s complaint followed a widely reviled March 2008 ITA advertising campaign that set out to dispel what it called myths about melanoma and skin cancer. Among other claims in that campaign, according to the FTC, the ITA claimed that indoor tanning is approved by the government, and that a National Academy of Sciences study showed the risk of not getting enough ultraviolet light outweighed the "hypothetical" risk of skin cancer.

So what does the ITA have to do to make amends?

Deceptive advertisements are barred. Health benefit claims for indoor tanning have to be substantiated. And advertisements have to carry the following boldfaced warning: "NOTICE: Exposure to ultraviolet radiation may increase the likelihood of developing skin cancer and can cause serious eye injury."

Although all four members of the FTC agreed that this settlement is proper, it is still subject to a 30-day comment period. That means indoor tanning enthusiasts have until Feb. 26 to try to change the agency’s mind. After that, the settlement is final.

--- Alicia Ault (on Twitter @aliciaault)

_{Image Courtesy Flickr user jasonippolito, Creative Commons attribution license}

The Indoor Tanning Association (ITA) is really feeling the heat these days.

The Food and Drug Administration (FDA) said it would finally act on congressional orders to take a closer look at tanning bed labels (see my earlier post), and now the Federal Trade Commission (FTC) said it has exacted a settlement from the ITA to cease and desist "false health and safety claims about indoor tanning."

The FTC said, "Contrary to claims in the association’s advertising, indoor tanning increases the risk of squamous cell and melanoma skin cancers."

The agency’s complaint followed a widely reviled March 2008 ITA advertising campaign that set out to dispel what it called myths about melanoma and skin cancer. Among other claims in that campaign, according to the FTC, the ITA claimed that indoor tanning is approved by the government, and that a National Academy of Sciences study showed the risk of not getting enough ultraviolet light outweighed the "hypothetical" risk of skin cancer.

So what does the ITA have to do to make amends?

Deceptive advertisements are barred. Health benefit claims for indoor tanning have to be substantiated. And advertisements have to carry the following boldfaced warning: "NOTICE: Exposure to ultraviolet radiation may increase the likelihood of developing skin cancer and can cause serious eye injury."

Although all four members of the FTC agreed that this settlement is proper, it is still subject to a 30-day comment period. That means indoor tanning enthusiasts have until Feb. 26 to try to change the agency’s mind. After that, the settlement is final.

--- Alicia Ault (on Twitter @aliciaault)

_{Image Courtesy Flickr user jasonippolito, Creative Commons attribution license}

The Indoor Tanning Association (ITA) is really feeling the heat these days.

The Food and Drug Administration (FDA) said it would finally act on congressional orders to take a closer look at tanning bed labels (see my earlier post), and now the Federal Trade Commission (FTC) said it has exacted a settlement from the ITA to cease and desist "false health and safety claims about indoor tanning."

The FTC said, "Contrary to claims in the association’s advertising, indoor tanning increases the risk of squamous cell and melanoma skin cancers."

The agency’s complaint followed a widely reviled March 2008 ITA advertising campaign that set out to dispel what it called myths about melanoma and skin cancer. Among other claims in that campaign, according to the FTC, the ITA claimed that indoor tanning is approved by the government, and that a National Academy of Sciences study showed the risk of not getting enough ultraviolet light outweighed the "hypothetical" risk of skin cancer.

So what does the ITA have to do to make amends?

Deceptive advertisements are barred. Health benefit claims for indoor tanning have to be substantiated. And advertisements have to carry the following boldfaced warning: "NOTICE: Exposure to ultraviolet radiation may increase the likelihood of developing skin cancer and can cause serious eye injury."

Although all four members of the FTC agreed that this settlement is proper, it is still subject to a 30-day comment period. That means indoor tanning enthusiasts have until Feb. 26 to try to change the agency’s mind. After that, the settlement is final.

--- Alicia Ault (on Twitter @aliciaault)

_{Image Courtesy Flickr user jasonippolito, Creative Commons attribution license}

ORLANDO — Daily application of 3.75% imiquimod cream with a 2-week dosing cycle was well tolerated and effective for treating actinic keratoses in adults, based on data from two studies.

In current treatment regimens, some patients use a 5% concentration imiquimod (Aldara, Graceway) cream twice a week over a treatment period as long as 16 weeks, but a lower dose may allow a shorter treatment period, said Dr. Neil Swanson of Oregon Health and Science University, Portland.

Dr. Swanson and his colleagues randomized 160 patients to 3.75% imiquimod cream, 160 patients to 2.5% imiquimod cream, and 159 patients to a placebo cream. The patients, aged 18 years and older, had 5-20 clinically diagnosed actinic keratoses (AKs) on the face or balding scalp. The study results were presented in a poster at the Orlando Dermatology Aesthetic and Clinical Conference.

Both the 3.75% and 2.5% creams were significantly more effective than placebo at fully clearing AKs after 2 weeks of daily use. Overall, 36% of the 3.75% group and 31% of the 2.5% group achieved complete clearance, vs. 6% of the placebo group.

The 3.75% cream, however, was significantly better than the 2.5% cream for partial clearance and lesion reduction. Approximately 60% of the 3.75% group achieved partial clearance (defined as at least 75%), compared with 48% of the 2.5% group and 23% of the placebo group.

Both concentrations of imiquimod were well tolerated, and most local skin reactions were mild to moderate. Local skin reactions occurred in 1% of the placebo group, 21% of the 2.5% group, and 34% of the 3.75% group. The most common local skin reactions in both groups were erythema, scabbing or crusting, and erosion or ulceration.

"Median percent lesion reduction of 81.8% was comparable to that observed for imiquimod 5% cream applied for 16 weeks in treating a smaller area of fewer lesions," the researchers noted. By comparison, the median lesion reduction from baseline was 71.8% in the 2.5% group and 25% in the placebo group. The average lesion count at baseline was 11 in all three groups.

Patients applied the treatment cream or placebo daily to the treatment areas for approximately 8 hours or overnight and then removed it. The study included two 2-week cycles separated by a 2-week no-treatment period.

In a companion study also presented as a poster at the meeting, there was no significant improvement in effectiveness with either imiquimod 2.5% or 3.75% cream for treating AKs when used daily for two 3-week cycles separated by a 3-week no-treatment period. The study randomized 164 patients to a placebo cream, 164 patients to imiquimod 2.5% cream, and 162 patients to imiquimod 3.75% cream.

Both imiquimod creams were adequately tolerated and significantly more effective than placebo, reported Dr. C. William Hanke, a dermatologic surgeon in Carmel, Ind., and colleagues.

When both studies were evaluated together, though, "efficacy was better with imiquimod 3.75% than with 2.5%. Extending the cycle duration from 2 weeks to 3 weeks did not further increase efficacy," Dr. Hanke and his associates wrote.

Both studies were funded by Graceway Pharmaceuticals. Both Dr. Swanson and Dr. Hanke have served as investigators and consultants for Graceway. Coauthors on both studies include other investigators, consultants, and employees of Graceway.

ORLANDO — Daily application of 3.75% imiquimod cream with a 2-week dosing cycle was well tolerated and effective for treating actinic keratoses in adults, based on data from two studies.

In current treatment regimens, some patients use a 5% concentration imiquimod (Aldara, Graceway) cream twice a week over a treatment period as long as 16 weeks, but a lower dose may allow a shorter treatment period, said Dr. Neil Swanson of Oregon Health and Science University, Portland.

Dr. Swanson and his colleagues randomized 160 patients to 3.75% imiquimod cream, 160 patients to 2.5% imiquimod cream, and 159 patients to a placebo cream. The patients, aged 18 years and older, had 5-20 clinically diagnosed actinic keratoses (AKs) on the face or balding scalp. The study results were presented in a poster at the Orlando Dermatology Aesthetic and Clinical Conference.

Both the 3.75% and 2.5% creams were significantly more effective than placebo at fully clearing AKs after 2 weeks of daily use. Overall, 36% of the 3.75% group and 31% of the 2.5% group achieved complete clearance, vs. 6% of the placebo group.

The 3.75% cream, however, was significantly better than the 2.5% cream for partial clearance and lesion reduction. Approximately 60% of the 3.75% group achieved partial clearance (defined as at least 75%), compared with 48% of the 2.5% group and 23% of the placebo group.

Both concentrations of imiquimod were well tolerated, and most local skin reactions were mild to moderate. Local skin reactions occurred in 1% of the placebo group, 21% of the 2.5% group, and 34% of the 3.75% group. The most common local skin reactions in both groups were erythema, scabbing or crusting, and erosion or ulceration.

"Median percent lesion reduction of 81.8% was comparable to that observed for imiquimod 5% cream applied for 16 weeks in treating a smaller area of fewer lesions," the researchers noted. By comparison, the median lesion reduction from baseline was 71.8% in the 2.5% group and 25% in the placebo group. The average lesion count at baseline was 11 in all three groups.

Patients applied the treatment cream or placebo daily to the treatment areas for approximately 8 hours or overnight and then removed it. The study included two 2-week cycles separated by a 2-week no-treatment period.

In a companion study also presented as a poster at the meeting, there was no significant improvement in effectiveness with either imiquimod 2.5% or 3.75% cream for treating AKs when used daily for two 3-week cycles separated by a 3-week no-treatment period. The study randomized 164 patients to a placebo cream, 164 patients to imiquimod 2.5% cream, and 162 patients to imiquimod 3.75% cream.

Both imiquimod creams were adequately tolerated and significantly more effective than placebo, reported Dr. C. William Hanke, a dermatologic surgeon in Carmel, Ind., and colleagues.

When both studies were evaluated together, though, "efficacy was better with imiquimod 3.75% than with 2.5%. Extending the cycle duration from 2 weeks to 3 weeks did not further increase efficacy," Dr. Hanke and his associates wrote.

Both studies were funded by Graceway Pharmaceuticals. Both Dr. Swanson and Dr. Hanke have served as investigators and consultants for Graceway. Coauthors on both studies include other investigators, consultants, and employees of Graceway.

ORLANDO — Daily application of 3.75% imiquimod cream with a 2-week dosing cycle was well tolerated and effective for treating actinic keratoses in adults, based on data from two studies.

In current treatment regimens, some patients use a 5% concentration imiquimod (Aldara, Graceway) cream twice a week over a treatment period as long as 16 weeks, but a lower dose may allow a shorter treatment period, said Dr. Neil Swanson of Oregon Health and Science University, Portland.

Dr. Swanson and his colleagues randomized 160 patients to 3.75% imiquimod cream, 160 patients to 2.5% imiquimod cream, and 159 patients to a placebo cream. The patients, aged 18 years and older, had 5-20 clinically diagnosed actinic keratoses (AKs) on the face or balding scalp. The study results were presented in a poster at the Orlando Dermatology Aesthetic and Clinical Conference.

Both the 3.75% and 2.5% creams were significantly more effective than placebo at fully clearing AKs after 2 weeks of daily use. Overall, 36% of the 3.75% group and 31% of the 2.5% group achieved complete clearance, vs. 6% of the placebo group.

The 3.75% cream, however, was significantly better than the 2.5% cream for partial clearance and lesion reduction. Approximately 60% of the 3.75% group achieved partial clearance (defined as at least 75%), compared with 48% of the 2.5% group and 23% of the placebo group.

Both concentrations of imiquimod were well tolerated, and most local skin reactions were mild to moderate. Local skin reactions occurred in 1% of the placebo group, 21% of the 2.5% group, and 34% of the 3.75% group. The most common local skin reactions in both groups were erythema, scabbing or crusting, and erosion or ulceration.

"Median percent lesion reduction of 81.8% was comparable to that observed for imiquimod 5% cream applied for 16 weeks in treating a smaller area of fewer lesions," the researchers noted. By comparison, the median lesion reduction from baseline was 71.8% in the 2.5% group and 25% in the placebo group. The average lesion count at baseline was 11 in all three groups.

Patients applied the treatment cream or placebo daily to the treatment areas for approximately 8 hours or overnight and then removed it. The study included two 2-week cycles separated by a 2-week no-treatment period.

In a companion study also presented as a poster at the meeting, there was no significant improvement in effectiveness with either imiquimod 2.5% or 3.75% cream for treating AKs when used daily for two 3-week cycles separated by a 3-week no-treatment period. The study randomized 164 patients to a placebo cream, 164 patients to imiquimod 2.5% cream, and 162 patients to imiquimod 3.75% cream.

Both imiquimod creams were adequately tolerated and significantly more effective than placebo, reported Dr. C. William Hanke, a dermatologic surgeon in Carmel, Ind., and colleagues.

When both studies were evaluated together, though, "efficacy was better with imiquimod 3.75% than with 2.5%. Extending the cycle duration from 2 weeks to 3 weeks did not further increase efficacy," Dr. Hanke and his associates wrote.

Both studies were funded by Graceway Pharmaceuticals. Both Dr. Swanson and Dr. Hanke have served as investigators and consultants for Graceway. Coauthors on both studies include other investigators, consultants, and employees of Graceway.

The Food and Drug Administration (FDA) has announced that it will finally be taking a closer look at the health effects of indoor tanning, starting with an advisory committee meeting on March 25.

Considering that the agency has taken a decade (and counting) to release regulations guiding the manufacture, composition and advertising of sunscreens, the FDA is acting relatively quickly on indoor tanning.

Dermatologists, cancer advocates, and pediatricians, among others, have been seeking some kind of stricter regulations on indoor tanning, or, more hopefully, an outright ban.  Many states and localities have begun to restrict the use of indoor tanning by minors. But, despite a wealth of evidence that excessive exposure to ultraviolet radiation, even when delivered indoors, leads to skin cancer, the federal government has not moved to more strictly police tanning salons.

Congress has been prodding the FDA for years.  In 2007, the Tanning Accountability and Notification Act was included in the Food and Drug Administration Amendments Act of 2007.  The TAN Act (see page 36 here) directed the FDA to study tanning bed warning labels that had been in place since 1985, with an eye towards making them more prominent and comprehensible by consumers. The FDA was then to report back to Congress.
In December 2008, the agency told lawmakers in its required report that it was considering updating the warning labels.  A series of focus groups led it to believe that maybe the almost-quarter-century-old labels might have reached their expiration date.

A year later, the FDA created a web page warning consumers about the dangers of tanning indoors.

And now, the advisory panel. According to the announcement, "There continues to be a growing body of literature showing association of skin cancer with use of tanning lamps and the committee will discuss this information and other information related to the association of UV and skin cancer (both melanoma and non-melanoma). The committee will be asked to recommend whether changes to current classification or current regulatory controls of UV emitting devices (lamps) used for tanning are needed."

Expect a lively discussion at the meeting, with likely appearances by tanning salon owners and the Indoor Tanning Association. Those groups are already unhappy about a 10% tax on tanning users that's being proposed as part of health reform.

The agency usually takes its' advisory committees' advice to heart.  We'll be keeping an eye on this panel's proceedings.

Alicia Ault (on Twitter @aliciaault)

_{Image courtesy Flickr user cogdogblog (cc)}

Read more at:

• Indoor Tanning Association online
• FDA Medical Devices Advisory Committee Meeting Annoucement

The Food and Drug Administration (FDA) has announced that it will finally be taking a closer look at the health effects of indoor tanning, starting with an advisory committee meeting on March 25.

Considering that the agency has taken a decade (and counting) to release regulations guiding the manufacture, composition and advertising of sunscreens, the FDA is acting relatively quickly on indoor tanning.

Dermatologists, cancer advocates, and pediatricians, among others, have been seeking some kind of stricter regulations on indoor tanning, or, more hopefully, an outright ban.  Many states and localities have begun to restrict the use of indoor tanning by minors. But, despite a wealth of evidence that excessive exposure to ultraviolet radiation, even when delivered indoors, leads to skin cancer, the federal government has not moved to more strictly police tanning salons.

Congress has been prodding the FDA for years.  In 2007, the Tanning Accountability and Notification Act was included in the Food and Drug Administration Amendments Act of 2007.  The TAN Act (see page 36 here) directed the FDA to study tanning bed warning labels that had been in place since 1985, with an eye towards making them more prominent and comprehensible by consumers. The FDA was then to report back to Congress.
In December 2008, the agency told lawmakers in its required report that it was considering updating the warning labels.  A series of focus groups led it to believe that maybe the almost-quarter-century-old labels might have reached their expiration date.

A year later, the FDA created a web page warning consumers about the dangers of tanning indoors.

And now, the advisory panel. According to the announcement, "There continues to be a growing body of literature showing association of skin cancer with use of tanning lamps and the committee will discuss this information and other information related to the association of UV and skin cancer (both melanoma and non-melanoma). The committee will be asked to recommend whether changes to current classification or current regulatory controls of UV emitting devices (lamps) used for tanning are needed."

Expect a lively discussion at the meeting, with likely appearances by tanning salon owners and the Indoor Tanning Association. Those groups are already unhappy about a 10% tax on tanning users that's being proposed as part of health reform.

The agency usually takes its' advisory committees' advice to heart.  We'll be keeping an eye on this panel's proceedings.

Alicia Ault (on Twitter @aliciaault)

_{Image courtesy Flickr user cogdogblog (cc)}

Read more at:

• Indoor Tanning Association online
• FDA Medical Devices Advisory Committee Meeting Annoucement

The Food and Drug Administration (FDA) has announced that it will finally be taking a closer look at the health effects of indoor tanning, starting with an advisory committee meeting on March 25.

Considering that the agency has taken a decade (and counting) to release regulations guiding the manufacture, composition and advertising of sunscreens, the FDA is acting relatively quickly on indoor tanning.

Dermatologists, cancer advocates, and pediatricians, among others, have been seeking some kind of stricter regulations on indoor tanning, or, more hopefully, an outright ban.  Many states and localities have begun to restrict the use of indoor tanning by minors. But, despite a wealth of evidence that excessive exposure to ultraviolet radiation, even when delivered indoors, leads to skin cancer, the federal government has not moved to more strictly police tanning salons.

Congress has been prodding the FDA for years.  In 2007, the Tanning Accountability and Notification Act was included in the Food and Drug Administration Amendments Act of 2007.  The TAN Act (see page 36 here) directed the FDA to study tanning bed warning labels that had been in place since 1985, with an eye towards making them more prominent and comprehensible by consumers. The FDA was then to report back to Congress.
In December 2008, the agency told lawmakers in its required report that it was considering updating the warning labels.  A series of focus groups led it to believe that maybe the almost-quarter-century-old labels might have reached their expiration date.

A year later, the FDA created a web page warning consumers about the dangers of tanning indoors.

And now, the advisory panel. According to the announcement, "There continues to be a growing body of literature showing association of skin cancer with use of tanning lamps and the committee will discuss this information and other information related to the association of UV and skin cancer (both melanoma and non-melanoma). The committee will be asked to recommend whether changes to current classification or current regulatory controls of UV emitting devices (lamps) used for tanning are needed."

Expect a lively discussion at the meeting, with likely appearances by tanning salon owners and the Indoor Tanning Association. Those groups are already unhappy about a 10% tax on tanning users that's being proposed as part of health reform.

The agency usually takes its' advisory committees' advice to heart.  We'll be keeping an eye on this panel's proceedings.

Alicia Ault (on Twitter @aliciaault)

_{Image courtesy Flickr user cogdogblog (cc)}

Read more at:

• Indoor Tanning Association online
• FDA Medical Devices Advisory Committee Meeting Annoucement

SAN DIEGO — Data on the estimated incidence of melanoma in the United States in 2010 from the National Cancer Institute's Surveillance, Epidemiology and End Results program will not be available until later this year, but Dr. Darrell S. Rigel does not expect the news to be good.

"Melanoma rates are rising significantly in the United States and in other parts of the world," he said at a melanoma update sponsored by the Scripps Clinic.

"Whatever criteria you use, it's clear that we're seeing more melanomas than we've seen in the past, and we'll probably continue to do so in the next 5-10 years."

According to the most recent SEER data, in 2009 there were 68,720 newly diagnosed cases of invasive melanoma and 53,120 cases of in situ melanoma. Dr. Rigel and his associates at the New York University Interdisciplinary Melanoma Cooperative Group estimate that the projected lifetime risk of invasive melanoma was 1:58 in 2009, up from 1:65 in 2004.

"Should that rate of increase continue, the risk will be about 1:50 by the year 2015," said Dr. Rigel, who is a professor of dermatology and dermatologic surgery at New York University Medical Center. "We've been pretty close on these projections over the last few years. One in 50 is a lot. That's 2% of the population."

Factor in the incidence of in situ melanoma, and the risk of any American getting any kind of melanoma jumps to 1:30, which would be 121,840 total cases in 2009.

"It's a significant problem," he said.

Nine years ago, researchers who analyzed the melanoma incidence rates in the United States from 1960-1997 forecasted a subsequent growing incidence of melanoma. They concluded that the increase in melanoma incidence is real - "not due to improved diagnosis," Dr. Rigel said - and predicted that the incidence would continue to rise for the next decade or more (J. Natl. Cancer Inst. 2001;93:67-83).

Results from studies published in the past decade suggest that the incidence of melanoma is also rising in other parts of the world. In Finland, for example, the incidence of melanoma increased from 1.5 cases to 12.8 cases per 100,000 men between 1953 and 2003, and from 1.8 cases to 10.4 cases per 100,000 women during the same time period (Int. J. Cancer 2006;119:380-4).

In central Greece, the incidence increased from 1.4 cases to 5.2 cases per 100,000 people between 1988 and 1998 (Int. J. Tissue React. 2005;27:173-9). Melanomas were most frequently located on the head and neck, extremities, and trunk.

In Columbia, the incidence of melanoma increased from 2.7 cases to 13 cases per 100,000 people between 2003 and 2005 (Rev. Salud Pública 2007;9:595-601).

Dr. Rigel emphasized that results from the best available studies in the medical literature suggest that the rising incidence of melanoma cannot be explained by increased surveillance, awareness, or by changing histologic criteria. However, while the number of melanoma deaths continues to rise, 5-year survival rates are improving - from 86% between 1985 and 1989 to 92% between 1995 and 2002 (Cancer J. Clin. 2007;57:43-66).

"That seems incongruous," Dr. Rigel said. "The only way that can be happening mathematically is that the incidence has to be rising even faster. That's a compelling reason to explain why the rising incidence is real. According to the World Health Organization, melanoma is rising faster than any other cancer worldwide, on a percentage basis."

He went on to note that the current incidence of melanoma is probably underreported because data from SEER are collected primarily from hospitals.
"The biopsy may be done in an outpatient setting," he explained. "It may go to an outpatient lab; it may be re-excised, and then it may go back to the same lab. It may never hit a hospital. That's why melanoma probably is significantly undercounted."

According to the American Cancer Society, melanoma kills one American citizen per hour. "Some people pooh-pooh skin cancer," Dr. Rigel said. "It's the most common cancer in women aged 25-29, and it's the number one cancer killer in women aged 30-35. There are some subsets of the population that are particularly hurt by this disease."

Dr. Rigel disclosed that he receives grants and advising and consulting fees from a number of pharmaceutical companies, including Neutrogena, Johnson & Johnson, Procter & Gamble, and Beiersdorf.

SAN DIEGO — Data on the estimated incidence of melanoma in the United States in 2010 from the National Cancer Institute's Surveillance, Epidemiology and End Results program will not be available until later this year, but Dr. Darrell S. Rigel does not expect the news to be good.

"Melanoma rates are rising significantly in the United States and in other parts of the world," he said at a melanoma update sponsored by the Scripps Clinic.

"Whatever criteria you use, it's clear that we're seeing more melanomas than we've seen in the past, and we'll probably continue to do so in the next 5-10 years."

According to the most recent SEER data, in 2009 there were 68,720 newly diagnosed cases of invasive melanoma and 53,120 cases of in situ melanoma. Dr. Rigel and his associates at the New York University Interdisciplinary Melanoma Cooperative Group estimate that the projected lifetime risk of invasive melanoma was 1:58 in 2009, up from 1:65 in 2004.

"Should that rate of increase continue, the risk will be about 1:50 by the year 2015," said Dr. Rigel, who is a professor of dermatology and dermatologic surgery at New York University Medical Center. "We've been pretty close on these projections over the last few years. One in 50 is a lot. That's 2% of the population."

Factor in the incidence of in situ melanoma, and the risk of any American getting any kind of melanoma jumps to 1:30, which would be 121,840 total cases in 2009.

"It's a significant problem," he said.

Nine years ago, researchers who analyzed the melanoma incidence rates in the United States from 1960-1997 forecasted a subsequent growing incidence of melanoma. They concluded that the increase in melanoma incidence is real - "not due to improved diagnosis," Dr. Rigel said - and predicted that the incidence would continue to rise for the next decade or more (J. Natl. Cancer Inst. 2001;93:67-83).

Results from studies published in the past decade suggest that the incidence of melanoma is also rising in other parts of the world. In Finland, for example, the incidence of melanoma increased from 1.5 cases to 12.8 cases per 100,000 men between 1953 and 2003, and from 1.8 cases to 10.4 cases per 100,000 women during the same time period (Int. J. Cancer 2006;119:380-4).

In central Greece, the incidence increased from 1.4 cases to 5.2 cases per 100,000 people between 1988 and 1998 (Int. J. Tissue React. 2005;27:173-9). Melanomas were most frequently located on the head and neck, extremities, and trunk.

In Columbia, the incidence of melanoma increased from 2.7 cases to 13 cases per 100,000 people between 2003 and 2005 (Rev. Salud Pública 2007;9:595-601).

Dr. Rigel emphasized that results from the best available studies in the medical literature suggest that the rising incidence of melanoma cannot be explained by increased surveillance, awareness, or by changing histologic criteria. However, while the number of melanoma deaths continues to rise, 5-year survival rates are improving - from 86% between 1985 and 1989 to 92% between 1995 and 2002 (Cancer J. Clin. 2007;57:43-66).

"That seems incongruous," Dr. Rigel said. "The only way that can be happening mathematically is that the incidence has to be rising even faster. That's a compelling reason to explain why the rising incidence is real. According to the World Health Organization, melanoma is rising faster than any other cancer worldwide, on a percentage basis."

He went on to note that the current incidence of melanoma is probably underreported because data from SEER are collected primarily from hospitals.
"The biopsy may be done in an outpatient setting," he explained. "It may go to an outpatient lab; it may be re-excised, and then it may go back to the same lab. It may never hit a hospital. That's why melanoma probably is significantly undercounted."

According to the American Cancer Society, melanoma kills one American citizen per hour. "Some people pooh-pooh skin cancer," Dr. Rigel said. "It's the most common cancer in women aged 25-29, and it's the number one cancer killer in women aged 30-35. There are some subsets of the population that are particularly hurt by this disease."

Dr. Rigel disclosed that he receives grants and advising and consulting fees from a number of pharmaceutical companies, including Neutrogena, Johnson & Johnson, Procter & Gamble, and Beiersdorf.

SAN DIEGO — Data on the estimated incidence of melanoma in the United States in 2010 from the National Cancer Institute's Surveillance, Epidemiology and End Results program will not be available until later this year, but Dr. Darrell S. Rigel does not expect the news to be good.

"Melanoma rates are rising significantly in the United States and in other parts of the world," he said at a melanoma update sponsored by the Scripps Clinic.

"Whatever criteria you use, it's clear that we're seeing more melanomas than we've seen in the past, and we'll probably continue to do so in the next 5-10 years."

According to the most recent SEER data, in 2009 there were 68,720 newly diagnosed cases of invasive melanoma and 53,120 cases of in situ melanoma. Dr. Rigel and his associates at the New York University Interdisciplinary Melanoma Cooperative Group estimate that the projected lifetime risk of invasive melanoma was 1:58 in 2009, up from 1:65 in 2004.

"Should that rate of increase continue, the risk will be about 1:50 by the year 2015," said Dr. Rigel, who is a professor of dermatology and dermatologic surgery at New York University Medical Center. "We've been pretty close on these projections over the last few years. One in 50 is a lot. That's 2% of the population."

Factor in the incidence of in situ melanoma, and the risk of any American getting any kind of melanoma jumps to 1:30, which would be 121,840 total cases in 2009.

"It's a significant problem," he said.

Nine years ago, researchers who analyzed the melanoma incidence rates in the United States from 1960-1997 forecasted a subsequent growing incidence of melanoma. They concluded that the increase in melanoma incidence is real - "not due to improved diagnosis," Dr. Rigel said - and predicted that the incidence would continue to rise for the next decade or more (J. Natl. Cancer Inst. 2001;93:67-83).

Results from studies published in the past decade suggest that the incidence of melanoma is also rising in other parts of the world. In Finland, for example, the incidence of melanoma increased from 1.5 cases to 12.8 cases per 100,000 men between 1953 and 2003, and from 1.8 cases to 10.4 cases per 100,000 women during the same time period (Int. J. Cancer 2006;119:380-4).

In central Greece, the incidence increased from 1.4 cases to 5.2 cases per 100,000 people between 1988 and 1998 (Int. J. Tissue React. 2005;27:173-9). Melanomas were most frequently located on the head and neck, extremities, and trunk.

In Columbia, the incidence of melanoma increased from 2.7 cases to 13 cases per 100,000 people between 2003 and 2005 (Rev. Salud Pública 2007;9:595-601).

Dr. Rigel emphasized that results from the best available studies in the medical literature suggest that the rising incidence of melanoma cannot be explained by increased surveillance, awareness, or by changing histologic criteria. However, while the number of melanoma deaths continues to rise, 5-year survival rates are improving - from 86% between 1985 and 1989 to 92% between 1995 and 2002 (Cancer J. Clin. 2007;57:43-66).

"That seems incongruous," Dr. Rigel said. "The only way that can be happening mathematically is that the incidence has to be rising even faster. That's a compelling reason to explain why the rising incidence is real. According to the World Health Organization, melanoma is rising faster than any other cancer worldwide, on a percentage basis."

He went on to note that the current incidence of melanoma is probably underreported because data from SEER are collected primarily from hospitals.
"The biopsy may be done in an outpatient setting," he explained. "It may go to an outpatient lab; it may be re-excised, and then it may go back to the same lab. It may never hit a hospital. That's why melanoma probably is significantly undercounted."

According to the American Cancer Society, melanoma kills one American citizen per hour. "Some people pooh-pooh skin cancer," Dr. Rigel said. "It's the most common cancer in women aged 25-29, and it's the number one cancer killer in women aged 30-35. There are some subsets of the population that are particularly hurt by this disease."

Dr. Rigel disclosed that he receives grants and advising and consulting fees from a number of pharmaceutical companies, including Neutrogena, Johnson & Johnson, Procter & Gamble, and Beiersdorf.

A little over 20 years ago, Dr. Hubert T. Greenway Jr. and Dr. Terry L. Barrett sat down in a hospital cafeteria and began to outline plans on a napkin for an annual conference to provide dermatologists, and other interested physicians and health care providers, with an update on the latest advances in the diagnosis and treatment of melanoma.

This past weekend in San Diego, the duo marked the 20th anniversary of the annual cutaneous malignancy update.

"As the course grew in popularity, and word got out about the content of the course, we were able to invite more faculty from across the country and get specific experts in their fields to bring us up to date on the new developments in melanoma," Dr. Barrett, professor of pathology and dermatology at the University of Texas, Southwestern School of Medicine in Dallas, recalled in an interview. "The course has evolved as the knowledge base has evolved."

Dr. Greenway, who chairs the division of Mohs and cutaneous surgery at Scripps Clinic, La Jolla, Calif., said that one important development over the 20-year life of the course has been sentinel node biopsy, which is used primarily as a diagnostic tool. "That has been a tremendous advance," said Dr. Greenway, who was fellowship trained by Dr. Frederic E. Mohs. "It’s brought forth the concept that melanoma requires a team [treatment approach]."

Even though the incidence of melanoma is likely to continue to rise over the next few years, Dr. Barrett noted that clinicians "have a much better understanding, statistics, and data on which to base prognosis and guide treatment."

As for the future, researchers studying the human genome and how it relates to the development of melanoma are "on the beginning of understanding," said Dr. Barrett, who is also director of ProPath Dermatopathology in Dallas. "In the next decade, I think we’re going to see an explosion of knowledge as it relates to molecular pathology and genetic understanding of the disease."

VIDEO:

• Watch the video interview of Drs. Barrett and Greenway on YouTube 

Doug Brunk (on Twitter @dougbrunk)
San Diego Bureau

A little over 20 years ago, Dr. Hubert T. Greenway Jr. and Dr. Terry L. Barrett sat down in a hospital cafeteria and began to outline plans on a napkin for an annual conference to provide dermatologists, and other interested physicians and health care providers, with an update on the latest advances in the diagnosis and treatment of melanoma.

This past weekend in San Diego, the duo marked the 20th anniversary of the annual cutaneous malignancy update.

"As the course grew in popularity, and word got out about the content of the course, we were able to invite more faculty from across the country and get specific experts in their fields to bring us up to date on the new developments in melanoma," Dr. Barrett, professor of pathology and dermatology at the University of Texas, Southwestern School of Medicine in Dallas, recalled in an interview. "The course has evolved as the knowledge base has evolved."

Dr. Greenway, who chairs the division of Mohs and cutaneous surgery at Scripps Clinic, La Jolla, Calif., said that one important development over the 20-year life of the course has been sentinel node biopsy, which is used primarily as a diagnostic tool. "That has been a tremendous advance," said Dr. Greenway, who was fellowship trained by Dr. Frederic E. Mohs. "It’s brought forth the concept that melanoma requires a team [treatment approach]."

Even though the incidence of melanoma is likely to continue to rise over the next few years, Dr. Barrett noted that clinicians "have a much better understanding, statistics, and data on which to base prognosis and guide treatment."

As for the future, researchers studying the human genome and how it relates to the development of melanoma are "on the beginning of understanding," said Dr. Barrett, who is also director of ProPath Dermatopathology in Dallas. "In the next decade, I think we’re going to see an explosion of knowledge as it relates to molecular pathology and genetic understanding of the disease."

VIDEO:

• Watch the video interview of Drs. Barrett and Greenway on YouTube 

Doug Brunk (on Twitter @dougbrunk)
San Diego Bureau

A little over 20 years ago, Dr. Hubert T. Greenway Jr. and Dr. Terry L. Barrett sat down in a hospital cafeteria and began to outline plans on a napkin for an annual conference to provide dermatologists, and other interested physicians and health care providers, with an update on the latest advances in the diagnosis and treatment of melanoma.

This past weekend in San Diego, the duo marked the 20th anniversary of the annual cutaneous malignancy update.

"As the course grew in popularity, and word got out about the content of the course, we were able to invite more faculty from across the country and get specific experts in their fields to bring us up to date on the new developments in melanoma," Dr. Barrett, professor of pathology and dermatology at the University of Texas, Southwestern School of Medicine in Dallas, recalled in an interview. "The course has evolved as the knowledge base has evolved."

Dr. Greenway, who chairs the division of Mohs and cutaneous surgery at Scripps Clinic, La Jolla, Calif., said that one important development over the 20-year life of the course has been sentinel node biopsy, which is used primarily as a diagnostic tool. "That has been a tremendous advance," said Dr. Greenway, who was fellowship trained by Dr. Frederic E. Mohs. "It’s brought forth the concept that melanoma requires a team [treatment approach]."

Even though the incidence of melanoma is likely to continue to rise over the next few years, Dr. Barrett noted that clinicians "have a much better understanding, statistics, and data on which to base prognosis and guide treatment."

As for the future, researchers studying the human genome and how it relates to the development of melanoma are "on the beginning of understanding," said Dr. Barrett, who is also director of ProPath Dermatopathology in Dallas. "In the next decade, I think we’re going to see an explosion of knowledge as it relates to molecular pathology and genetic understanding of the disease."

VIDEO:

• Watch the video interview of Drs. Barrett and Greenway on YouTube 

Doug Brunk (on Twitter @dougbrunk)
San Diego Bureau

Voriconazole, approved for use against serious fungal infections in 2002, has been linked to five more cases of melanoma in situ in two patients, according to a report published online Jan. 18 in the Archives of Dermatology.

Both patients, aged 20 and 39 years, first exhibited photosensitivity followed by extensive photodamage before the lesions were identified in affected areas.

These cases, even added to the four already reported in the literature, are not enough to establish that the drug plays “a definitive causal role” in skin malignancy. However, “we believe that the presence of accelerated photodamage in [two relatively young] patients, coupled with the recent reports supporting an association between voriconazole use and [aggressive] squamous cell carcinoma, warrant further exploration of the role of the drug in skin cancer formation,” said Dr. Daniel D. Miller of the University of California, San Francisco, and his associates (Arch Dermatol. 2010 [doi:10.1001/archdermatol.2009.362]).

“Until such studies further define the skin cancer risk associated with voriconazole, we recommend surveillance for skin cancer formation in all patients who require long-term voriconazole treatment, particularly those who manifest signs or symptoms of photosensitivity or chronic photodamage,” the investigators noted.

They described the two most recent patients in case reports.

The first patient was a 39-year-old woman who was first referred for severe photosensitivity and extensive lentigines on the photoexposed surfaces of the face, upper trunk, and extensor extremities. There was no personal or family history of photosensitivity or skin cancer.

The woman lived in an area endemic for coccidioidomycosis and had been receiving oral voriconazole for 3 years to treat coccidioidomycosis meningitis. Severe erythema with eruptive pigmented macules had developed 1 year after starting treatment.

Histopathology of a specimen taken from an erythematous macule on the right helix showed melanoma in situ.

Five months later, Dr. Miller and his colleagues discovered another ill-defined lesion on the patient —“a brownish blue patch within a field of solar lentigines on severely sun-damaged skin on the mid-upper chest”— that proved to be another melanoma in situ.

One year later, two additional in situ melanomas were identified on the right forearm and the dorsal surface of the left hand. Voriconazole therapy was discontinued, and the patient continues to be monitored for suspicious skin lesions every 3-6 months.

In the second case, an adolescent male with chronic granulomatous disease had been taking long-term voriconazole to treat pulmonary Aspergillus infection. After 2 years of the therapy, he had begun to develop lentigines on sun-exposed areas of his body, including the face, forearms, and dorsal surfaces of his hands.

At age 20 years, after 55 months of treatment, an irregular, darkly pigmented macule on his left forearm was found to be melanoma in situ. His therapy was switched from voriconazole to posaconazole. No subsequent lesions have been identified, and the patient reports fading of his extensive lentigines since discontinuing voriconazole.

The courses of these two patients are clinically similar to what happens in patients who undergo long-term PUVA therapy and in those with xeroderma pigmentosum. However, in the two case reports, "the rapid onset of extensive lentigines, as well as the short interval of voriconazole therapy before melanoma developed (relative to that seen due to PUVA), suggest perhaps an even more accelerated process of carcinogenesis," Dr. Miller and his colleagues said.

“Future comparisons between xeroderma pigmentosum-associated melanomas and those occurring in the setting of voriconazole-associated phototoxic effects may provide valuable insight into the contribution of UV light to melanoma genesis,” they added.

Dr. Miller reported no relevant conflicts of interest.

Voriconazole, approved for use against serious fungal infections in 2002, has been linked to five more cases of melanoma in situ in two patients, according to a report published online Jan. 18 in the Archives of Dermatology.

Both patients, aged 20 and 39 years, first exhibited photosensitivity followed by extensive photodamage before the lesions were identified in affected areas.

These cases, even added to the four already reported in the literature, are not enough to establish that the drug plays “a definitive causal role” in skin malignancy. However, “we believe that the presence of accelerated photodamage in [two relatively young] patients, coupled with the recent reports supporting an association between voriconazole use and [aggressive] squamous cell carcinoma, warrant further exploration of the role of the drug in skin cancer formation,” said Dr. Daniel D. Miller of the University of California, San Francisco, and his associates (Arch Dermatol. 2010 [doi:10.1001/archdermatol.2009.362]).

“Until such studies further define the skin cancer risk associated with voriconazole, we recommend surveillance for skin cancer formation in all patients who require long-term voriconazole treatment, particularly those who manifest signs or symptoms of photosensitivity or chronic photodamage,” the investigators noted.

They described the two most recent patients in case reports.

The first patient was a 39-year-old woman who was first referred for severe photosensitivity and extensive lentigines on the photoexposed surfaces of the face, upper trunk, and extensor extremities. There was no personal or family history of photosensitivity or skin cancer.

The woman lived in an area endemic for coccidioidomycosis and had been receiving oral voriconazole for 3 years to treat coccidioidomycosis meningitis. Severe erythema with eruptive pigmented macules had developed 1 year after starting treatment.

Histopathology of a specimen taken from an erythematous macule on the right helix showed melanoma in situ.

Five months later, Dr. Miller and his colleagues discovered another ill-defined lesion on the patient —“a brownish blue patch within a field of solar lentigines on severely sun-damaged skin on the mid-upper chest”— that proved to be another melanoma in situ.

One year later, two additional in situ melanomas were identified on the right forearm and the dorsal surface of the left hand. Voriconazole therapy was discontinued, and the patient continues to be monitored for suspicious skin lesions every 3-6 months.

In the second case, an adolescent male with chronic granulomatous disease had been taking long-term voriconazole to treat pulmonary Aspergillus infection. After 2 years of the therapy, he had begun to develop lentigines on sun-exposed areas of his body, including the face, forearms, and dorsal surfaces of his hands.

At age 20 years, after 55 months of treatment, an irregular, darkly pigmented macule on his left forearm was found to be melanoma in situ. His therapy was switched from voriconazole to posaconazole. No subsequent lesions have been identified, and the patient reports fading of his extensive lentigines since discontinuing voriconazole.

The courses of these two patients are clinically similar to what happens in patients who undergo long-term PUVA therapy and in those with xeroderma pigmentosum. However, in the two case reports, "the rapid onset of extensive lentigines, as well as the short interval of voriconazole therapy before melanoma developed (relative to that seen due to PUVA), suggest perhaps an even more accelerated process of carcinogenesis," Dr. Miller and his colleagues said.

“Future comparisons between xeroderma pigmentosum-associated melanomas and those occurring in the setting of voriconazole-associated phototoxic effects may provide valuable insight into the contribution of UV light to melanoma genesis,” they added.

Dr. Miller reported no relevant conflicts of interest.

Voriconazole, approved for use against serious fungal infections in 2002, has been linked to five more cases of melanoma in situ in two patients, according to a report published online Jan. 18 in the Archives of Dermatology.

Both patients, aged 20 and 39 years, first exhibited photosensitivity followed by extensive photodamage before the lesions were identified in affected areas.

These cases, even added to the four already reported in the literature, are not enough to establish that the drug plays “a definitive causal role” in skin malignancy. However, “we believe that the presence of accelerated photodamage in [two relatively young] patients, coupled with the recent reports supporting an association between voriconazole use and [aggressive] squamous cell carcinoma, warrant further exploration of the role of the drug in skin cancer formation,” said Dr. Daniel D. Miller of the University of California, San Francisco, and his associates (Arch Dermatol. 2010 [doi:10.1001/archdermatol.2009.362]).

“Until such studies further define the skin cancer risk associated with voriconazole, we recommend surveillance for skin cancer formation in all patients who require long-term voriconazole treatment, particularly those who manifest signs or symptoms of photosensitivity or chronic photodamage,” the investigators noted.

They described the two most recent patients in case reports.

The first patient was a 39-year-old woman who was first referred for severe photosensitivity and extensive lentigines on the photoexposed surfaces of the face, upper trunk, and extensor extremities. There was no personal or family history of photosensitivity or skin cancer.

The woman lived in an area endemic for coccidioidomycosis and had been receiving oral voriconazole for 3 years to treat coccidioidomycosis meningitis. Severe erythema with eruptive pigmented macules had developed 1 year after starting treatment.

Histopathology of a specimen taken from an erythematous macule on the right helix showed melanoma in situ.

Five months later, Dr. Miller and his colleagues discovered another ill-defined lesion on the patient —“a brownish blue patch within a field of solar lentigines on severely sun-damaged skin on the mid-upper chest”— that proved to be another melanoma in situ.

One year later, two additional in situ melanomas were identified on the right forearm and the dorsal surface of the left hand. Voriconazole therapy was discontinued, and the patient continues to be monitored for suspicious skin lesions every 3-6 months.

In the second case, an adolescent male with chronic granulomatous disease had been taking long-term voriconazole to treat pulmonary Aspergillus infection. After 2 years of the therapy, he had begun to develop lentigines on sun-exposed areas of his body, including the face, forearms, and dorsal surfaces of his hands.

At age 20 years, after 55 months of treatment, an irregular, darkly pigmented macule on his left forearm was found to be melanoma in situ. His therapy was switched from voriconazole to posaconazole. No subsequent lesions have been identified, and the patient reports fading of his extensive lentigines since discontinuing voriconazole.

The courses of these two patients are clinically similar to what happens in patients who undergo long-term PUVA therapy and in those with xeroderma pigmentosum. However, in the two case reports, "the rapid onset of extensive lentigines, as well as the short interval of voriconazole therapy before melanoma developed (relative to that seen due to PUVA), suggest perhaps an even more accelerated process of carcinogenesis," Dr. Miller and his colleagues said.

“Future comparisons between xeroderma pigmentosum-associated melanomas and those occurring in the setting of voriconazole-associated phototoxic effects may provide valuable insight into the contribution of UV light to melanoma genesis,” they added.

Dr. Miller reported no relevant conflicts of interest.

Oral celecoxib inhibited basal cell carcinoma carcinogenesis in mice and had a chemopreventive effect on basal cell carcinoma in humans with less severe disease, results from a novel investigation demonstrated.

The findings, published in Cancer Prevention Research, help to explain what causes basal cell carcinoma tumors, lead study author Jean Y. Tang said in an interview.

"We always used to think that BCC was caused only by mutations in the hedgehog pathway," said Dr. Tang of Stanford (Calif.) University. "Now we know that the [cyclooxygenase] enzyme is also important for BCC development. That means we can find drugs that target COX. That should prevent or treat BCCs."

She and her associates conducted two trials: one in mice and one in humans.

For the mouse trial, the investigators compared the relative anti-BCC effects of genetic deletion and nonsteroidal anti-inflammatory pharmacologic inhibition of cyclooxygenase enzymes in the skin of Ptch+/- mice (Cancer Prev. Res. 2010; 3[1]:25-34).

For the phase II human trial, which began in May of 2001 at four clinical sites, 60 patients with basal cell nevus syndrome were randomized to placebo or to 200 mg celecoxib twice daily for 24 months. Patients with this syndrome are genetically predisposed to developing multiple basal cell carcinomas.

Participants returned to the study sites every 3 months for physical examinations, which included the measurement and counting of BCCs.

Patients discontinued taking study medications in December 2004 after news of potential cardiovascular adverse events in persons treated with celecoxib (N. Engl. J. Med. 2005;352:1071-80).

In the mouse trial, genetic deletion of COX1 or COX2 decreased microscopic tumor burden by 75% while pharmacologic inhibition with celecoxib reduced microscopic BCCs by 35%. "That tells us that the [COX] enzyme is important for BCC tumor development," Dr. Tang said.

In the human trial, patients in the placebo group had a 37% increase of BCCs per year, compared with a 26% increase among patients in the celecoxib group, a difference that was not statistically significant. However, when the researchers stratified patients by the number of BCC tumors at baseline (fewer than 15 vs. 15 or more), celecoxib reduced the change in the number of BCCs in patients with fewer than 15 BCCs at baseline (48% vs. 22% in the placebo group) but did not have an effect in patients with 15 or more BCCs at baseline.

"That's the surprising part," Dr. Tang commented. "We were hoping that this drug would have more of an impact on the patients with really severe disease."

The researchers also found that patients in the placebo group who had fewer than 15 BCCs at baseline had a 50% increase in BCC burden per year, while patients in the celecoxib group had a 20% increase, a difference that was statistically significant.

Dr. Tang said that the findings "open the field for people to explore other drugs that inhibit the COX enzymes for BCC treatment or prevention. There are safer drugs that don't have as much cardiovascular toxicity [as celecoxib]. For example, aspirin, ibuprofen, and other COX1 and COX2 inhibitors may work."

She acknowledged certain limitations of the study, including the fact that the human trial was limited to 60 patients with basal cell nevus syndrome, which is also known as Gorlin's syndrome. "Most patients with sporadic BCCs don't have the Gorlin's syndrome," she explained. "So we don't know if celecoxib would work against sporadic BCCs in non-Gorlin's patients."

In an accompanying editorial, Dr. Charles M. Rudin of the department of oncology at Johns Hopkins University, Baltimore, called the findings "encouraging" but emphasized that they should be interpreted with caution (Cancer Prev. Res. 2010; 3[1]:1-3).

"In each of their several murine experiments, the effect of genetic or pharmacologic COX inhibition on tumor burden was predominantly attributable to a decrease in tumor size, with a lesser, if any, effect in reducing tumor number," he noted. "This result suggests that the primary effect of COX inhibition may be on proliferation rate rather than on malignant transformation per se. In this scenario, the reported minor decreases in tumor number could reflect maintenance of a small number of tumors at a size below clinical detection. These observations may be reminiscent of the differentiating effects of retinoids, which may suppress tumorigenesis, but in a transient and thus questionable manner."

The researchers had no conflicts of interest to disclose.

The study was funded by grants from the National Institutes of Health, the Mike Rainen Family Foundation, and the National Center for Research Resources (University of California, San Francisco).

Oral celecoxib inhibited basal cell carcinoma carcinogenesis in mice and had a chemopreventive effect on basal cell carcinoma in humans with less severe disease, results from a novel investigation demonstrated.

The findings, published in Cancer Prevention Research, help to explain what causes basal cell carcinoma tumors, lead study author Jean Y. Tang said in an interview.

"We always used to think that BCC was caused only by mutations in the hedgehog pathway," said Dr. Tang of Stanford (Calif.) University. "Now we know that the [cyclooxygenase] enzyme is also important for BCC development. That means we can find drugs that target COX. That should prevent or treat BCCs."

She and her associates conducted two trials: one in mice and one in humans.

For the mouse trial, the investigators compared the relative anti-BCC effects of genetic deletion and nonsteroidal anti-inflammatory pharmacologic inhibition of cyclooxygenase enzymes in the skin of Ptch+/- mice (Cancer Prev. Res. 2010; 3[1]:25-34).

For the phase II human trial, which began in May of 2001 at four clinical sites, 60 patients with basal cell nevus syndrome were randomized to placebo or to 200 mg celecoxib twice daily for 24 months. Patients with this syndrome are genetically predisposed to developing multiple basal cell carcinomas.

Participants returned to the study sites every 3 months for physical examinations, which included the measurement and counting of BCCs.

Patients discontinued taking study medications in December 2004 after news of potential cardiovascular adverse events in persons treated with celecoxib (N. Engl. J. Med. 2005;352:1071-80).

In the mouse trial, genetic deletion of COX1 or COX2 decreased microscopic tumor burden by 75% while pharmacologic inhibition with celecoxib reduced microscopic BCCs by 35%. "That tells us that the [COX] enzyme is important for BCC tumor development," Dr. Tang said.

In the human trial, patients in the placebo group had a 37% increase of BCCs per year, compared with a 26% increase among patients in the celecoxib group, a difference that was not statistically significant. However, when the researchers stratified patients by the number of BCC tumors at baseline (fewer than 15 vs. 15 or more), celecoxib reduced the change in the number of BCCs in patients with fewer than 15 BCCs at baseline (48% vs. 22% in the placebo group) but did not have an effect in patients with 15 or more BCCs at baseline.

"That's the surprising part," Dr. Tang commented. "We were hoping that this drug would have more of an impact on the patients with really severe disease."

The researchers also found that patients in the placebo group who had fewer than 15 BCCs at baseline had a 50% increase in BCC burden per year, while patients in the celecoxib group had a 20% increase, a difference that was statistically significant.

Dr. Tang said that the findings "open the field for people to explore other drugs that inhibit the COX enzymes for BCC treatment or prevention. There are safer drugs that don't have as much cardiovascular toxicity [as celecoxib]. For example, aspirin, ibuprofen, and other COX1 and COX2 inhibitors may work."

She acknowledged certain limitations of the study, including the fact that the human trial was limited to 60 patients with basal cell nevus syndrome, which is also known as Gorlin's syndrome. "Most patients with sporadic BCCs don't have the Gorlin's syndrome," she explained. "So we don't know if celecoxib would work against sporadic BCCs in non-Gorlin's patients."

In an accompanying editorial, Dr. Charles M. Rudin of the department of oncology at Johns Hopkins University, Baltimore, called the findings "encouraging" but emphasized that they should be interpreted with caution (Cancer Prev. Res. 2010; 3[1]:1-3).

"In each of their several murine experiments, the effect of genetic or pharmacologic COX inhibition on tumor burden was predominantly attributable to a decrease in tumor size, with a lesser, if any, effect in reducing tumor number," he noted. "This result suggests that the primary effect of COX inhibition may be on proliferation rate rather than on malignant transformation per se. In this scenario, the reported minor decreases in tumor number could reflect maintenance of a small number of tumors at a size below clinical detection. These observations may be reminiscent of the differentiating effects of retinoids, which may suppress tumorigenesis, but in a transient and thus questionable manner."

The researchers had no conflicts of interest to disclose.

The study was funded by grants from the National Institutes of Health, the Mike Rainen Family Foundation, and the National Center for Research Resources (University of California, San Francisco).

Oral celecoxib inhibited basal cell carcinoma carcinogenesis in mice and had a chemopreventive effect on basal cell carcinoma in humans with less severe disease, results from a novel investigation demonstrated.

The findings, published in Cancer Prevention Research, help to explain what causes basal cell carcinoma tumors, lead study author Jean Y. Tang said in an interview.

"We always used to think that BCC was caused only by mutations in the hedgehog pathway," said Dr. Tang of Stanford (Calif.) University. "Now we know that the [cyclooxygenase] enzyme is also important for BCC development. That means we can find drugs that target COX. That should prevent or treat BCCs."

She and her associates conducted two trials: one in mice and one in humans.

For the mouse trial, the investigators compared the relative anti-BCC effects of genetic deletion and nonsteroidal anti-inflammatory pharmacologic inhibition of cyclooxygenase enzymes in the skin of Ptch+/- mice (Cancer Prev. Res. 2010; 3[1]:25-34).

For the phase II human trial, which began in May of 2001 at four clinical sites, 60 patients with basal cell nevus syndrome were randomized to placebo or to 200 mg celecoxib twice daily for 24 months. Patients with this syndrome are genetically predisposed to developing multiple basal cell carcinomas.

Participants returned to the study sites every 3 months for physical examinations, which included the measurement and counting of BCCs.

Patients discontinued taking study medications in December 2004 after news of potential cardiovascular adverse events in persons treated with celecoxib (N. Engl. J. Med. 2005;352:1071-80).

In the mouse trial, genetic deletion of COX1 or COX2 decreased microscopic tumor burden by 75% while pharmacologic inhibition with celecoxib reduced microscopic BCCs by 35%. "That tells us that the [COX] enzyme is important for BCC tumor development," Dr. Tang said.

In the human trial, patients in the placebo group had a 37% increase of BCCs per year, compared with a 26% increase among patients in the celecoxib group, a difference that was not statistically significant. However, when the researchers stratified patients by the number of BCC tumors at baseline (fewer than 15 vs. 15 or more), celecoxib reduced the change in the number of BCCs in patients with fewer than 15 BCCs at baseline (48% vs. 22% in the placebo group) but did not have an effect in patients with 15 or more BCCs at baseline.

"That's the surprising part," Dr. Tang commented. "We were hoping that this drug would have more of an impact on the patients with really severe disease."

The researchers also found that patients in the placebo group who had fewer than 15 BCCs at baseline had a 50% increase in BCC burden per year, while patients in the celecoxib group had a 20% increase, a difference that was statistically significant.

Dr. Tang said that the findings "open the field for people to explore other drugs that inhibit the COX enzymes for BCC treatment or prevention. There are safer drugs that don't have as much cardiovascular toxicity [as celecoxib]. For example, aspirin, ibuprofen, and other COX1 and COX2 inhibitors may work."

She acknowledged certain limitations of the study, including the fact that the human trial was limited to 60 patients with basal cell nevus syndrome, which is also known as Gorlin's syndrome. "Most patients with sporadic BCCs don't have the Gorlin's syndrome," she explained. "So we don't know if celecoxib would work against sporadic BCCs in non-Gorlin's patients."

In an accompanying editorial, Dr. Charles M. Rudin of the department of oncology at Johns Hopkins University, Baltimore, called the findings "encouraging" but emphasized that they should be interpreted with caution (Cancer Prev. Res. 2010; 3[1]:1-3).

"In each of their several murine experiments, the effect of genetic or pharmacologic COX inhibition on tumor burden was predominantly attributable to a decrease in tumor size, with a lesser, if any, effect in reducing tumor number," he noted. "This result suggests that the primary effect of COX inhibition may be on proliferation rate rather than on malignant transformation per se. In this scenario, the reported minor decreases in tumor number could reflect maintenance of a small number of tumors at a size below clinical detection. These observations may be reminiscent of the differentiating effects of retinoids, which may suppress tumorigenesis, but in a transient and thus questionable manner."

The researchers had no conflicts of interest to disclose.

The study was funded by grants from the National Institutes of Health, the Mike Rainen Family Foundation, and the National Center for Research Resources (University of California, San Francisco).

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DermaDoctor Inc.

www.dermadoctor.com

DermaDoctor Body Guard SPF-30 sunscreen works to avert sun damage on the face and body. The formulation contains the antioxidant epigallocatechin gallate (EGCG), the active ingredient in green tea, to counter UV damage to the skin. It also contains sebum-sequestering microparticles, which reduce excess surface oils that are already present on the skin, as well as botanicals for soothing and sodium hyaluronate for moisturizing. The product is noncomedogenic and leaves a matte finish. A tube of the sunscreen retails for about $25.

DermaDoctor Inc.

www.dermadoctor.com

DermaDoctor Body Guard SPF-30 sunscreen works to avert sun damage on the face and body. The formulation contains the antioxidant epigallocatechin gallate (EGCG), the active ingredient in green tea, to counter UV damage to the skin. It also contains sebum-sequestering microparticles, which reduce excess surface oils that are already present on the skin, as well as botanicals for soothing and sodium hyaluronate for moisturizing. The product is noncomedogenic and leaves a matte finish. A tube of the sunscreen retails for about $25.

DermaDoctor Inc.

www.dermadoctor.com