Melanoma

Community Oncology Editor Dr. Jame Abraham spoke with Dr. Michael Postow at the Oncology Practice Summit in Las Vegas about new immuno- and targeted therapies for melanoma, their side effects, and early phase studies of emerging therapies.

The Oncology Practice Summit was the 8th annual meeting of Community Oncology, the journal of clinical issues in community practice.  Dr. Abraham was a co-chair of the Summit, which was hosted this year by Community Oncology as well as The Journal of Supportive Oncology, and The Oncology Report.

Community Oncology Editor Dr. Jame Abraham spoke with Dr. Michael Postow at the Oncology Practice Summit in Las Vegas about new immuno- and targeted therapies for melanoma, their side effects, and early phase studies of emerging therapies.

The Oncology Practice Summit was the 8th annual meeting of Community Oncology, the journal of clinical issues in community practice.  Dr. Abraham was a co-chair of the Summit, which was hosted this year by Community Oncology as well as The Journal of Supportive Oncology, and The Oncology Report.

Community Oncology Editor Dr. Jame Abraham spoke with Dr. Michael Postow at the Oncology Practice Summit in Las Vegas about new immuno- and targeted therapies for melanoma, their side effects, and early phase studies of emerging therapies.

The Oncology Practice Summit was the 8th annual meeting of Community Oncology, the journal of clinical issues in community practice.  Dr. Abraham was a co-chair of the Summit, which was hosted this year by Community Oncology as well as The Journal of Supportive Oncology, and The Oncology Report.

MIAMI BEACH – Vismodegib treatment for 3 months prior to Mohs surgery for operable basal cell carcinomas shrunk tumors by 46% and reduced the Mohs defect size by 38%, based on data from an open-label intervention trial. The findings were reported at the annual meeting of the American Academy of Dermatology.

The estimated Mohs surgical defect area (based on tumor size) in the first five patients treated in the single-arm study decreased by a mean of 1.4 cm² from baseline, and actual Mohs surgical defect size decreased by 1.1 cm² after a mean of 3.4 months of treatment with vismodegib. The changes were statistically significant.

The Mohs defect size was considered a secondary endpoint, because actual defect size can be influenced by skin tension and lesion location, said Dr. Mina Ally, a research fellow at Stanford (Calif.) University.

Patients included in the study were five adults with a total of seven basal cell carcinomas (BCCs) of varying histologic subtypes. One occurred on the shoulder, and the rest occurred on the face; one was a recurrence. All patients were treated for at least 3 months at a vismodegib dosage of 150 mg daily, and all required only a single Mohs stage of excision.

Vismodegib, an oral hedgehog pathway inhibitor approved for the indefinite treatment of advanced and metastatic basal cell carcinomas (that result from aberrant hedgehog pathway signaling), was generally safe, said Dr. Ally.

"All patients experienced mild grade 1 side effects, including muscle cramps, hair loss, and taste loss, and we only needed to discontinue the medication early – after 2 months – in one patient due to a grade 2 elevation in liver enzymes," she said, noting that all of the adverse events resolved after treatment discontinuation.

Further sectioning of Mohs specimens revealed no evidence of residual BCC in three cases and residual BCC in one case. The diagnosis was equivocal in the remaining cases.

"This was because we were seeing an increased number of aberrant follicular structures after (vismodegib) treatment, which were sometimes difficult to differentiate from residual BCC," Dr. Ally explained.

Further staining using a panel that included pleckstrin homology-like domain, family A, member 1, a hair follicle stem cell marker, helped differentiate the follicular structures from BCC, she noted.

None of the patients experienced tumor recurrence during a median 5 months of follow-up.

The findings are of interest because about 1 million people in the United States are affected by BCCs each year, said Dr. Ally. While vismodegib appears to represent a useful adjuvant therapy when given for 3 months prior to Mohs surgery in some cases, certain challenges must be overcome, she said.

"Suppression of the Hedgehog pathway does appear to alter normal follicular development, and this was causing us difficulty in analyzing our histology specimens," Dr. Ally noted. "Future challenges really lie in interpreting these histology specimens and being able to differentiate these follicular structures from residual BCC, which can confound tumor margin clearance."

Dr. Ally reported having no disclosures.

MIAMI BEACH – Vismodegib treatment for 3 months prior to Mohs surgery for operable basal cell carcinomas shrunk tumors by 46% and reduced the Mohs defect size by 38%, based on data from an open-label intervention trial. The findings were reported at the annual meeting of the American Academy of Dermatology.

The estimated Mohs surgical defect area (based on tumor size) in the first five patients treated in the single-arm study decreased by a mean of 1.4 cm² from baseline, and actual Mohs surgical defect size decreased by 1.1 cm² after a mean of 3.4 months of treatment with vismodegib. The changes were statistically significant.

The Mohs defect size was considered a secondary endpoint, because actual defect size can be influenced by skin tension and lesion location, said Dr. Mina Ally, a research fellow at Stanford (Calif.) University.

Patients included in the study were five adults with a total of seven basal cell carcinomas (BCCs) of varying histologic subtypes. One occurred on the shoulder, and the rest occurred on the face; one was a recurrence. All patients were treated for at least 3 months at a vismodegib dosage of 150 mg daily, and all required only a single Mohs stage of excision.

Vismodegib, an oral hedgehog pathway inhibitor approved for the indefinite treatment of advanced and metastatic basal cell carcinomas (that result from aberrant hedgehog pathway signaling), was generally safe, said Dr. Ally.

"All patients experienced mild grade 1 side effects, including muscle cramps, hair loss, and taste loss, and we only needed to discontinue the medication early – after 2 months – in one patient due to a grade 2 elevation in liver enzymes," she said, noting that all of the adverse events resolved after treatment discontinuation.

Further sectioning of Mohs specimens revealed no evidence of residual BCC in three cases and residual BCC in one case. The diagnosis was equivocal in the remaining cases.

"This was because we were seeing an increased number of aberrant follicular structures after (vismodegib) treatment, which were sometimes difficult to differentiate from residual BCC," Dr. Ally explained.

Further staining using a panel that included pleckstrin homology-like domain, family A, member 1, a hair follicle stem cell marker, helped differentiate the follicular structures from BCC, she noted.

None of the patients experienced tumor recurrence during a median 5 months of follow-up.

The findings are of interest because about 1 million people in the United States are affected by BCCs each year, said Dr. Ally. While vismodegib appears to represent a useful adjuvant therapy when given for 3 months prior to Mohs surgery in some cases, certain challenges must be overcome, she said.

"Suppression of the Hedgehog pathway does appear to alter normal follicular development, and this was causing us difficulty in analyzing our histology specimens," Dr. Ally noted. "Future challenges really lie in interpreting these histology specimens and being able to differentiate these follicular structures from residual BCC, which can confound tumor margin clearance."

Dr. Ally reported having no disclosures.

MIAMI BEACH – Vismodegib treatment for 3 months prior to Mohs surgery for operable basal cell carcinomas shrunk tumors by 46% and reduced the Mohs defect size by 38%, based on data from an open-label intervention trial. The findings were reported at the annual meeting of the American Academy of Dermatology.

The estimated Mohs surgical defect area (based on tumor size) in the first five patients treated in the single-arm study decreased by a mean of 1.4 cm² from baseline, and actual Mohs surgical defect size decreased by 1.1 cm² after a mean of 3.4 months of treatment with vismodegib. The changes were statistically significant.

The Mohs defect size was considered a secondary endpoint, because actual defect size can be influenced by skin tension and lesion location, said Dr. Mina Ally, a research fellow at Stanford (Calif.) University.

Patients included in the study were five adults with a total of seven basal cell carcinomas (BCCs) of varying histologic subtypes. One occurred on the shoulder, and the rest occurred on the face; one was a recurrence. All patients were treated for at least 3 months at a vismodegib dosage of 150 mg daily, and all required only a single Mohs stage of excision.

Vismodegib, an oral hedgehog pathway inhibitor approved for the indefinite treatment of advanced and metastatic basal cell carcinomas (that result from aberrant hedgehog pathway signaling), was generally safe, said Dr. Ally.

"All patients experienced mild grade 1 side effects, including muscle cramps, hair loss, and taste loss, and we only needed to discontinue the medication early – after 2 months – in one patient due to a grade 2 elevation in liver enzymes," she said, noting that all of the adverse events resolved after treatment discontinuation.

Further sectioning of Mohs specimens revealed no evidence of residual BCC in three cases and residual BCC in one case. The diagnosis was equivocal in the remaining cases.

"This was because we were seeing an increased number of aberrant follicular structures after (vismodegib) treatment, which were sometimes difficult to differentiate from residual BCC," Dr. Ally explained.

Further staining using a panel that included pleckstrin homology-like domain, family A, member 1, a hair follicle stem cell marker, helped differentiate the follicular structures from BCC, she noted.

None of the patients experienced tumor recurrence during a median 5 months of follow-up.

The findings are of interest because about 1 million people in the United States are affected by BCCs each year, said Dr. Ally. While vismodegib appears to represent a useful adjuvant therapy when given for 3 months prior to Mohs surgery in some cases, certain challenges must be overcome, she said.

"Suppression of the Hedgehog pathway does appear to alter normal follicular development, and this was causing us difficulty in analyzing our histology specimens," Dr. Ally noted. "Future challenges really lie in interpreting these histology specimens and being able to differentiate these follicular structures from residual BCC, which can confound tumor margin clearance."

Dr. Ally reported having no disclosures.

A radioactive diagnostic imaging agent called Lymphoseek (technetium Tc 99m tilmanocept) Injection has been approved for locating lymph nodes in patients who have breast cancer or melanoma and are undergoing surgery to remove tumor-draining lymph nodes, the Food and Drug Administration announced.

Lymphoseek is the first new drug for lymph-node mapping to be approved in more than 30 years. Other FDA-approved drugs used for lymph-node mapping include sulfur colloid and isosulfan blue.

"To use Lymphoseek, doctors inject the drug into the tumor area and later, using a handheld radiation detector, find lymph nodes that have taken up Lymphoseek’s radioactivity," said Dr. Shaw Chen, deputy director of the Office of Drug Evaluation IV in the FDA’s Center for Drug Evaluation and Research.

Lymphoseek is marketed by Navidea Biopharmaceuticals. The manufacturer’s website notes that the ability to rapidly locate and biopsy sentinel nodes enables surgical management to be tailored specifically to each patient’s burden of disease.

In two clinical trials, 332 patients with melanoma or breast cancer were injected with Lymphoseek and blue dye. Surgeons subsequently removed suspected lymph nodes for pathologic examination. Confirmed lymph nodes were examined for their content of blue dye and Lymphoseek. The combination of Lymphoseek and blue dye localized most lymph nodes, although a notable number of nodes were localized only by Lymphoseek.

The most common side effects identified in clinical trials were pain and irritation at the injection site.

According to the manufacturer, a clinical trial involving patients with head and neck cancer is completing enrollment and is expected to be the subject of a future New Drug Application amendment. An initial Marketing Authorization Application filing in the European Union is anticipated by the end of 2012.

[email protected]

A radioactive diagnostic imaging agent called Lymphoseek (technetium Tc 99m tilmanocept) Injection has been approved for locating lymph nodes in patients who have breast cancer or melanoma and are undergoing surgery to remove tumor-draining lymph nodes, the Food and Drug Administration announced.

Lymphoseek is the first new drug for lymph-node mapping to be approved in more than 30 years. Other FDA-approved drugs used for lymph-node mapping include sulfur colloid and isosulfan blue.

"To use Lymphoseek, doctors inject the drug into the tumor area and later, using a handheld radiation detector, find lymph nodes that have taken up Lymphoseek’s radioactivity," said Dr. Shaw Chen, deputy director of the Office of Drug Evaluation IV in the FDA’s Center for Drug Evaluation and Research.

Lymphoseek is marketed by Navidea Biopharmaceuticals. The manufacturer’s website notes that the ability to rapidly locate and biopsy sentinel nodes enables surgical management to be tailored specifically to each patient’s burden of disease.

In two clinical trials, 332 patients with melanoma or breast cancer were injected with Lymphoseek and blue dye. Surgeons subsequently removed suspected lymph nodes for pathologic examination. Confirmed lymph nodes were examined for their content of blue dye and Lymphoseek. The combination of Lymphoseek and blue dye localized most lymph nodes, although a notable number of nodes were localized only by Lymphoseek.

The most common side effects identified in clinical trials were pain and irritation at the injection site.

According to the manufacturer, a clinical trial involving patients with head and neck cancer is completing enrollment and is expected to be the subject of a future New Drug Application amendment. An initial Marketing Authorization Application filing in the European Union is anticipated by the end of 2012.

[email protected]

A radioactive diagnostic imaging agent called Lymphoseek (technetium Tc 99m tilmanocept) Injection has been approved for locating lymph nodes in patients who have breast cancer or melanoma and are undergoing surgery to remove tumor-draining lymph nodes, the Food and Drug Administration announced.

Lymphoseek is the first new drug for lymph-node mapping to be approved in more than 30 years. Other FDA-approved drugs used for lymph-node mapping include sulfur colloid and isosulfan blue.

"To use Lymphoseek, doctors inject the drug into the tumor area and later, using a handheld radiation detector, find lymph nodes that have taken up Lymphoseek’s radioactivity," said Dr. Shaw Chen, deputy director of the Office of Drug Evaluation IV in the FDA’s Center for Drug Evaluation and Research.

Lymphoseek is marketed by Navidea Biopharmaceuticals. The manufacturer’s website notes that the ability to rapidly locate and biopsy sentinel nodes enables surgical management to be tailored specifically to each patient’s burden of disease.

In two clinical trials, 332 patients with melanoma or breast cancer were injected with Lymphoseek and blue dye. Surgeons subsequently removed suspected lymph nodes for pathologic examination. Confirmed lymph nodes were examined for their content of blue dye and Lymphoseek. The combination of Lymphoseek and blue dye localized most lymph nodes, although a notable number of nodes were localized only by Lymphoseek.

The most common side effects identified in clinical trials were pain and irritation at the injection site.

According to the manufacturer, a clinical trial involving patients with head and neck cancer is completing enrollment and is expected to be the subject of a future New Drug Application amendment. An initial Marketing Authorization Application filing in the European Union is anticipated by the end of 2012.

[email protected]

Postmenopausal women who used aspirin regularly had a significantly lower risk of melanoma in an observational study from the Women’s Health Initiative including nearly 60,000 women, according to results published online in Cancer on March 11.

The longer the women took aspirin, the lower their risk for melanoma. Acetaminophen and other NSAIDs had no protective effects.

©jimdeli/Fotolia.com

"These findings suggest that aspirin may have a chemopreventive effect against the development of melanoma, and further clinical investigation is warranted," senior investigator and dermatologist Jean Tang of Stanford (Calif.) University and her colleagues concluded (Cancer 2013 March 11 [doi: 10.1002/cncr.27817]).

The analysis included 59,806 white, postmenopausal women aged 50-79 years who completed questionnaires about their aspirin and NSAID use as part of the Women’s Health Initiative, a federally funded effort to address the most common causes of death, disability, and impaired quality of life in postmenopausal women.

At baseline, 25% of the women reported regular aspirin use (defined as use of aspirin at least twice in the past 2 weeks). Of these, 75% reported using regular or extrastrength aspirin. A total of 15% of the women reported nonaspirin NSAID use at least twice in the prior 2 weeks. Ibuprofen and naproxen were the most commonly used nonaspirin NSAIDS. Approximately 60% of the women reported no regular use of aspirin or other NSAIDs.

The women were asked again about their aspirin and NSAID use at a second clinical visit after 3 years; 59% of aspirin users and 38% of NSAID users reported the same levels of medication use.

A total of 548 incident melanomas occurred during a median follow-up of 12 years: 289 melanomas in situ, 255 invasive melanomas, and 4 cases classified as unknown. The risk of melanoma was 21% lower in regular aspirin users compared with women who reported no aspirin use (hazard ratio, 0.79). Increased duration of aspirin use (less than 1 year, 1-4 years, and 5 years or more) was associated with an 11% lower risk of melanoma for each categorical increase.

In addition, the risk of melanoma was 30% lower in women who used aspirin regularly for 5 or more years (HR, 0.70). The incidence of melanoma per 100,000 person-years was 69.8, 87.9, and 87.1 for aspirin users, nonaspirin NSAID users, and NSAID and aspirin nonusers, respectively.

Dr. Tang and her colleagues controlled for skin cancer histories, sun exposure, sunscreen use, and other potential confounders in their analysis. At baseline, "the most important predictors of melanoma risk, prior nonmelanoma skin cancer and melanoma history, did not differ among the groups," they noted.

Although previous studies have shown a protective effect for aspirin and other NSAIDs against gastric, colorectal, and breast cancers, the results for melanoma have been mixed, possibly because negative studies used too low a dose of aspirin or the dosing was too infrequent, the researchers noted.

Similarly, infrequent use of nonaspirin NSAIDs may account for their lack of benefit in the trial, or "aspirin may have properties that other non[aspirin] NSAIDs lack," the investigators noted.

"Our finding that increased duration of aspirin use was associated with lower risk of melanoma after extended follow-up is consistent with studies of other malignancies, particularly colorectal cancer, that reported benefit after several years of aspirin use and extended follow-up. ... Cardiovascular benefits and potential antitumor effects of aspirin are particularly intriguing in the context of preventive medicine, but they must be weighed against well-known risks, such as gastrointestinal bleeding," they wrote.

The study was sponsored in part by the National Heart, Lung, and Blood Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Tang is a consultant for Genentech.

Postmenopausal women who used aspirin regularly had a significantly lower risk of melanoma in an observational study from the Women’s Health Initiative including nearly 60,000 women, according to results published online in Cancer on March 11.

The longer the women took aspirin, the lower their risk for melanoma. Acetaminophen and other NSAIDs had no protective effects.

©jimdeli/Fotolia.com

"These findings suggest that aspirin may have a chemopreventive effect against the development of melanoma, and further clinical investigation is warranted," senior investigator and dermatologist Jean Tang of Stanford (Calif.) University and her colleagues concluded (Cancer 2013 March 11 [doi: 10.1002/cncr.27817]).

The analysis included 59,806 white, postmenopausal women aged 50-79 years who completed questionnaires about their aspirin and NSAID use as part of the Women’s Health Initiative, a federally funded effort to address the most common causes of death, disability, and impaired quality of life in postmenopausal women.

At baseline, 25% of the women reported regular aspirin use (defined as use of aspirin at least twice in the past 2 weeks). Of these, 75% reported using regular or extrastrength aspirin. A total of 15% of the women reported nonaspirin NSAID use at least twice in the prior 2 weeks. Ibuprofen and naproxen were the most commonly used nonaspirin NSAIDS. Approximately 60% of the women reported no regular use of aspirin or other NSAIDs.

The women were asked again about their aspirin and NSAID use at a second clinical visit after 3 years; 59% of aspirin users and 38% of NSAID users reported the same levels of medication use.

A total of 548 incident melanomas occurred during a median follow-up of 12 years: 289 melanomas in situ, 255 invasive melanomas, and 4 cases classified as unknown. The risk of melanoma was 21% lower in regular aspirin users compared with women who reported no aspirin use (hazard ratio, 0.79). Increased duration of aspirin use (less than 1 year, 1-4 years, and 5 years or more) was associated with an 11% lower risk of melanoma for each categorical increase.

In addition, the risk of melanoma was 30% lower in women who used aspirin regularly for 5 or more years (HR, 0.70). The incidence of melanoma per 100,000 person-years was 69.8, 87.9, and 87.1 for aspirin users, nonaspirin NSAID users, and NSAID and aspirin nonusers, respectively.

Dr. Tang and her colleagues controlled for skin cancer histories, sun exposure, sunscreen use, and other potential confounders in their analysis. At baseline, "the most important predictors of melanoma risk, prior nonmelanoma skin cancer and melanoma history, did not differ among the groups," they noted.

Although previous studies have shown a protective effect for aspirin and other NSAIDs against gastric, colorectal, and breast cancers, the results for melanoma have been mixed, possibly because negative studies used too low a dose of aspirin or the dosing was too infrequent, the researchers noted.

Similarly, infrequent use of nonaspirin NSAIDs may account for their lack of benefit in the trial, or "aspirin may have properties that other non[aspirin] NSAIDs lack," the investigators noted.

"Our finding that increased duration of aspirin use was associated with lower risk of melanoma after extended follow-up is consistent with studies of other malignancies, particularly colorectal cancer, that reported benefit after several years of aspirin use and extended follow-up. ... Cardiovascular benefits and potential antitumor effects of aspirin are particularly intriguing in the context of preventive medicine, but they must be weighed against well-known risks, such as gastrointestinal bleeding," they wrote.

The study was sponsored in part by the National Heart, Lung, and Blood Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Tang is a consultant for Genentech.

Postmenopausal women who used aspirin regularly had a significantly lower risk of melanoma in an observational study from the Women’s Health Initiative including nearly 60,000 women, according to results published online in Cancer on March 11.

The longer the women took aspirin, the lower their risk for melanoma. Acetaminophen and other NSAIDs had no protective effects.

©jimdeli/Fotolia.com

"These findings suggest that aspirin may have a chemopreventive effect against the development of melanoma, and further clinical investigation is warranted," senior investigator and dermatologist Jean Tang of Stanford (Calif.) University and her colleagues concluded (Cancer 2013 March 11 [doi: 10.1002/cncr.27817]).

The analysis included 59,806 white, postmenopausal women aged 50-79 years who completed questionnaires about their aspirin and NSAID use as part of the Women’s Health Initiative, a federally funded effort to address the most common causes of death, disability, and impaired quality of life in postmenopausal women.

At baseline, 25% of the women reported regular aspirin use (defined as use of aspirin at least twice in the past 2 weeks). Of these, 75% reported using regular or extrastrength aspirin. A total of 15% of the women reported nonaspirin NSAID use at least twice in the prior 2 weeks. Ibuprofen and naproxen were the most commonly used nonaspirin NSAIDS. Approximately 60% of the women reported no regular use of aspirin or other NSAIDs.

The women were asked again about their aspirin and NSAID use at a second clinical visit after 3 years; 59% of aspirin users and 38% of NSAID users reported the same levels of medication use.

A total of 548 incident melanomas occurred during a median follow-up of 12 years: 289 melanomas in situ, 255 invasive melanomas, and 4 cases classified as unknown. The risk of melanoma was 21% lower in regular aspirin users compared with women who reported no aspirin use (hazard ratio, 0.79). Increased duration of aspirin use (less than 1 year, 1-4 years, and 5 years or more) was associated with an 11% lower risk of melanoma for each categorical increase.

In addition, the risk of melanoma was 30% lower in women who used aspirin regularly for 5 or more years (HR, 0.70). The incidence of melanoma per 100,000 person-years was 69.8, 87.9, and 87.1 for aspirin users, nonaspirin NSAID users, and NSAID and aspirin nonusers, respectively.

Dr. Tang and her colleagues controlled for skin cancer histories, sun exposure, sunscreen use, and other potential confounders in their analysis. At baseline, "the most important predictors of melanoma risk, prior nonmelanoma skin cancer and melanoma history, did not differ among the groups," they noted.

Although previous studies have shown a protective effect for aspirin and other NSAIDs against gastric, colorectal, and breast cancers, the results for melanoma have been mixed, possibly because negative studies used too low a dose of aspirin or the dosing was too infrequent, the researchers noted.

Similarly, infrequent use of nonaspirin NSAIDs may account for their lack of benefit in the trial, or "aspirin may have properties that other non[aspirin] NSAIDs lack," the investigators noted.

"Our finding that increased duration of aspirin use was associated with lower risk of melanoma after extended follow-up is consistent with studies of other malignancies, particularly colorectal cancer, that reported benefit after several years of aspirin use and extended follow-up. ... Cardiovascular benefits and potential antitumor effects of aspirin are particularly intriguing in the context of preventive medicine, but they must be weighed against well-known risks, such as gastrointestinal bleeding," they wrote.

The study was sponsored in part by the National Heart, Lung, and Blood Institute and the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Dr. Tang is a consultant for Genentech.

Noninvasive procedural dermatology has evolved at a dizzying pace, and continues to do so.

In addition to an array of procedures for skin tightening, skin resurfacing, and fat reduction, emerging technologies such as complex feedback devices, nanotechnology, and stem cell–based therapies promise to keep dermatology at the forefront of the cosmetic and esthetic realm, according to Dr. Murad Alam.

In an article featured in the March issue of Seminars in Cutaneous Medicine and Surgery, Dr. Alam of Northwestern University, Chicago, makes several predictions about the future of these technologies (Semin. Cutan. Med. Surg. 2013;32:61-63).

For example, like modern vehicles equipped with computer chips that can change steering and braking in response to environmental conditions, dermatologic devices will soon include technology that uses precise feedback to make automated setting changes, he said.

"Over time, the reduced cost of microelectronics, feedback controls, and computing power is simplifying the capacity of devices to analyze intraoperative information and adjust the procedure to compensate. For instance, certain laser and energy devices already have tips that are able to sense the temperature in the microenvironment and adjust power output to maintain site-specific temperature within a narrow band," he explained.

This technology could increase effectiveness and improve the safety of devices by reducing the level of operator time and expertise needed, and by making setting changes faster than humanly possible.

Autonomous nanotechnology devices are another advance described by Dr. Alam.

Miniaturization will become more feasible and affordable, and eventually devices will become "so exceedingly small that they will be mostly disposable and deployed in large numbers to the treatment site," he said.

The concept of hundreds of minuscule machines deployed to resurface skin or repair a wound may sound like science fiction, but the rapid advances in nanotechnology could make it a reality that could lead to the creation of new procedures such as ways to treat scars that can’t be corrected using currently available technologies, he added.

Dr. Alam’s other predictions for the future of noninvasive procedural dermatology included:

• Optimization of minimally invasive procedures for fat reduction and skin tightening, which currently provide only mild to modest results and longevity.

• The use of stem cells for augmentation of tissue layers, which could provide genuine rejuvenation rather than simply repair and concealment.

• The improvement of artificial dermal substitutes that can develop many of the functions of live skin, and can be grafted without inducing contractures.

• The development of rapid treatments for pigmentation using nanotechnology and cellular therapies, which will allow for precise melanocyte and melanosome transfer and automatic recoloration of discolored skin.

While these technologies continue to emerge, plenty of others have already established their places in the dermatology arena. The many and varied applications of one of these – low-level laser therapy, or LLLT – are described in another article in the March issue of Seminars in Cutaneous Medicine and Surgery (Semin. Cutan. Med. Surg. 2013;32:42-54).

"LLLT involves exposing cells or tissue to low levels of red and near-infrared light. ... Recently, medical treatment with LLLT at various intensities has been found to stimulate or inhibit an assortment of cellular processes," wrote Dr. Pinar Avci of Massachusetts General Hospital, Boston, and his colleagues, noting that the mechanism associated with the cellular photobiostimulation by LLLT is not yet fully understood, but appears to have a wide range of effects at the molecular, cellular, and tissue levels.

Describing LLLT as "possibly the ultimate noninvasive approach to treating the skin," the researchers highlighted numerous existing or emerging applications for the technology, outlined below.

Skin rejuvenation

Many modalities developed to reverse the dermal and epidermal signs of photoaging and chronological aging depend on the removal of the epidermis and the induction of a controlled form of skin wounding to promote collagen biosynthesis and dermal matrix remodeling. Examples include retinoic acid, dermabrasion, chemical peels, and ablative laser resurfacing.

These modalities require intensive posttreatment care and prolonged down time, and are associated with a risk of numerous complications, the researchers said.

LLLT represents an alternative that is known to increase microcirculation and vascular perfusion in the skin. Data from previous studies have shown that LLLT increased collagen and improved wrinkles and skin laxity with less down time and risk than that of other treatments.

In one study, for example, 300 patients treated with only a light-emitting diode (LED) LLLT device set at 590 nm, 0.10 J/cm², were compared with 600 patients who received the LED therapy in combination with a thermal-based photorejuvenation procedure. Of those who received LED therapy alone, 90% reported softer skin and less roughness and fine lines. The changes ranged from subtle to significant.

Those who received thermal photorejuvenation laser treatment reported a reduction in posttreatment erythema and an overall impression of increased efficacy with the additional LED treatment – an effect that could be attributed to anti-inflammatory effects of LLLT, they noted.

In another study, more than 90% of 90 patients receiving eight LED treatments over 4 weeks experienced favorable results, improving by at least one Fitzpatrick photoaging category. In addition, 65% of patients experienced global improvement in facial texture, fine lines, background erythema, and pigmentation, with results peaking 4-6 months after completion.

Acne treatment

LLLT in the red to near-infrared (NIR) spectral range (630-1000 nm) and with nonthermal power (less than 200 mW) has been shown in several studies to improve acne vulgaris. In one study, a significant reduction in active acne lesions occurred after 12 twice-weekly sessions using 630 nm red-spectrum LLLT with a fluence of 12 J/cm² in conjunction with 2% topical clindamycin. No significant effects were seen using an 890-nm laser. Other studies have demonstrated that the combination of blue and red light is synergistic for treating acne.

Photoprotection

Recent suggestions that infrared exposure might have protective effects against ultraviolet light–induced skin damage are based on the theory that the exposure might trigger protective or repair responses to UV irradiation. While controversial, this view is supported by data suggesting potential mechanisms of action. For example, some data suggest a role of p53, a sensor of gene integrity involved in cell apoptosis and repair mechanisms. In one study, the response to infrared (IR) irradiation was shown to be p53 dependent, suggesting the IR irradiation prepares cells to resist and/or repair further UV-induced DNA damage. Data from another study showed that IR irradiation induced the protective protein ferritin, which is involved in skin repair.

Data from yet another study suggested that nerve growth factor (NGF) production induced by LLLT using the helium neon semiconductor laser diode (HeNe, 633 nm) might explain the photoprotective effects of LLLT. In that study, NGF – a major paracrine maintenance factor for melanocyte survival in skin, was shown to protect melanocytes from UV-induced apoptosis by upregulating the level of Bcl-2 (an antiapoptotic protein) in the cells.

Herpesvirus lesion treatment

New therapies are needed to shorten recurrent herpesvirus episodes and reduce related pain and inflammation. LLLT has been suggested as an alternative to current medications. In one study of 50 patients with recurrent perioral HSV infection, LLLT at 690 nm, 80 mW/cm², 48 J/cm² daily for 2 weeks during recurrence-free periods decreased the frequency of herpes labialis episodes, the authors said.

In another study with similar parameters, patients achieved a significant prolongation of remission intervals from 30 to 73 days.

The mechanism of action remains unclear, but an indirect effect of LLLT on cellular and humoral components of the immune system may be involved in antiviral responses, as opposed to a direct virus-inactivating effect, the researchers noted.

Vitiligo treatment

Modest efficacy seen with the low-energy HeNe laser (632 nm, 25 mW/cm²) for the treatment of 18 vitiligo patients led to speculation that LLLT could serve as an alternative effective treatment for this typically treatment-resistant condition. (Repigmentation was observed in 64%, and some follicular repigmentation was observed in the remaining patients).

In a subsequent study of local administration of the HeNe laser light at 3 J/cm², 1.0 mW, 632.8 nm in patients with segmental type vitiligo, marked perilesional and perifollicular repigmentation of more than 50% was observed in 60% of patients.

"Both NGF and (basic fibroblast growth factor) stimulate melanocyte migration, and deficiencies of these mediators may participate in the development of vitiligo," the researchers wrote.

Depigmentation

During tests of red and blue light for acne, researchers unexpectedly found that patients treated with both red and blue light experienced an overall decrease in melanin.

Based on instrumental measurement results, blue light exposure (415 nm, 40 mW/cm², 48 J/cm²), increased the melanin level by 6.7, whereas red light exposure (633 nm, 80 mW/cm², 96 J/cm²) decreased the melanin level by 15.5.

"This finding may have some relationship with the laser’s brightening effect of the skin tone, which 14 of 24 patients spontaneously reported after the treatment period. However, as of today, no other studies investigated or reported a similar decrease in melanin levels after red light irradiations," the researchers said.

Hypertrophic scar and keloid eradication

LLLT has shown promise for preventing hypertrophic and keloid scars in patients who undergo scar revision by surgery or CO₂ laser. The use of daily near-infrared LED (NIR-LED) treatment on one of the two bilateral sites safely reduced the risk of scar development in that lesion, compared with the untreated lesion in three patients with bilateral scars. One underwent surgical revision/excision for preauricular linear keloids that developed after a face-lift procedure, one underwent CO₂ resurfacing for hypertrophic acne scars on the chest, and one underwent CO₂ resurfacing after excision of hypertrophic scars on the back. No significant treatment-related adverse effects were reported.

LLLT may work in these types of scars through an inhibitory effect on interleukin-6 mRNA levels and the modulating of platelet derived growth factor, transforming growth factor–beta, interleukins, and MMPs, which are associated with abnormal wound healing, the researchers noted.

Burn treatment

LED exposure was shown to provide benefit for the treatment of acute sunburn in a study of 10 patients.

Treatment once or twice daily for 3 days on half of the affected area decreased symptoms of burning, redness, swelling, and peeling compared with the untreated half. Decreased MMP-1 was noted on the treated side through immunofluorescence staining in one patient, and real-time polymerase chain reaction gene expression analysis showed a significant decrease in MMP-1 gene expression at both 4 and 24 hours after the UV injury on the treated side.

In another study, LED treatment was effective compared with control for speeding the healing process of laser treatment–related burns. In nine patients with second-degree burns from nonablative laser devices, LED therapy once daily for 1 week was associated with 50% faster healing based on both patient and physician accounts.

LED treatment also was shown in a pilot study to accelerate re-epithelialization of a forearm injury induced by a CO₂ laser; identical test sites were treated with daily dressing changes and polysporin ointment, but the site with faster re-epithelialization had also received the LED treatment (a computer pattern generator was used to deliver the identical CO₂ treatment to both sites).

Psoriasis

LLLT also shows promise for the treatment of plaque psoriasis. In a preliminary study, the combined use of sequential NIR (830 nm) and visible red light (630 nm) led to resolution of psoriasis in patients who were resistant to conventional therapy. The patients received treatment in two 20-minute sessions, 48 hours apart, for 4 or 5 weeks. No adverse side effects occurred.

Despite the variety of potential applications for the technology, LLLT remains somewhat controversial due to "uncertainties about the fundamental molecular and cellular mechanisms responsible for transducing signals from the photons incident on the cells to the biological effects that take place in the irradiated tissue" and because "there are significant variations in terms of dosimetry parameter: wavelength, irradiance or power density, pulse structure, coherence, polarization, energy, fluence, irradiation time, contact versus noncontact application, and repetition regimen," the researchers said.

They noted, however, that problems that have been experienced with LLLT – as well as negative study results – could be the result of inappropriate parameters, skin preparation, and/or device maintenance.

"LLLT appears to have a wide range of applications in dermatology, especially in indications where stimulation of healing, reduction of inflammation, reduction of cell death, and skin rejuvenation are required," they noted, but added that the lack of agreement on important parameters (particularly whether red, NIR, or a combination of both is optimal for a given application) has created a credibility gap that must be overcome before LLLT is routinely applied in every dermatologist’s office.

Once LLLT does become so widely accepted, however, it may be time for dermatologists to move on to the next big thing, Dr. Alam said in his article on the future of procedural dermatology.

"For several decades, dermatologists have worked closely with start-up companies to commercialize new devices and technologies ... when new toxins, fillers, and energy devices have been marketed, dermatologists have been early adopters," he said. "Over time, each device or procedure has diminished in cost and exclusivity as other physicians and nonphysicians have entered the market, and dermatologists have moved on to greener pastures. In all likelihood, this cycle will continue," he noted. "Dermatologists cannot prevent the dissemination of stable technologies, but they can continue to innovate and create new ones."

In fact, he added, continued success in this arena will rest largely on clinicians’ ability to nurture innovation to ensure a healthy pipeline of novel technologies.

The authors of the articles had no financial conflicts to disclose.

Noninvasive procedural dermatology has evolved at a dizzying pace, and continues to do so.

In addition to an array of procedures for skin tightening, skin resurfacing, and fat reduction, emerging technologies such as complex feedback devices, nanotechnology, and stem cell–based therapies promise to keep dermatology at the forefront of the cosmetic and esthetic realm, according to Dr. Murad Alam.

In an article featured in the March issue of Seminars in Cutaneous Medicine and Surgery, Dr. Alam of Northwestern University, Chicago, makes several predictions about the future of these technologies (Semin. Cutan. Med. Surg. 2013;32:61-63).

For example, like modern vehicles equipped with computer chips that can change steering and braking in response to environmental conditions, dermatologic devices will soon include technology that uses precise feedback to make automated setting changes, he said.

"Over time, the reduced cost of microelectronics, feedback controls, and computing power is simplifying the capacity of devices to analyze intraoperative information and adjust the procedure to compensate. For instance, certain laser and energy devices already have tips that are able to sense the temperature in the microenvironment and adjust power output to maintain site-specific temperature within a narrow band," he explained.

This technology could increase effectiveness and improve the safety of devices by reducing the level of operator time and expertise needed, and by making setting changes faster than humanly possible.

Autonomous nanotechnology devices are another advance described by Dr. Alam.

Miniaturization will become more feasible and affordable, and eventually devices will become "so exceedingly small that they will be mostly disposable and deployed in large numbers to the treatment site," he said.

The concept of hundreds of minuscule machines deployed to resurface skin or repair a wound may sound like science fiction, but the rapid advances in nanotechnology could make it a reality that could lead to the creation of new procedures such as ways to treat scars that can’t be corrected using currently available technologies, he added.

Dr. Alam’s other predictions for the future of noninvasive procedural dermatology included:

• Optimization of minimally invasive procedures for fat reduction and skin tightening, which currently provide only mild to modest results and longevity.

• The use of stem cells for augmentation of tissue layers, which could provide genuine rejuvenation rather than simply repair and concealment.

• The improvement of artificial dermal substitutes that can develop many of the functions of live skin, and can be grafted without inducing contractures.

• The development of rapid treatments for pigmentation using nanotechnology and cellular therapies, which will allow for precise melanocyte and melanosome transfer and automatic recoloration of discolored skin.

While these technologies continue to emerge, plenty of others have already established their places in the dermatology arena. The many and varied applications of one of these – low-level laser therapy, or LLLT – are described in another article in the March issue of Seminars in Cutaneous Medicine and Surgery (Semin. Cutan. Med. Surg. 2013;32:42-54).

"LLLT involves exposing cells or tissue to low levels of red and near-infrared light. ... Recently, medical treatment with LLLT at various intensities has been found to stimulate or inhibit an assortment of cellular processes," wrote Dr. Pinar Avci of Massachusetts General Hospital, Boston, and his colleagues, noting that the mechanism associated with the cellular photobiostimulation by LLLT is not yet fully understood, but appears to have a wide range of effects at the molecular, cellular, and tissue levels.

Describing LLLT as "possibly the ultimate noninvasive approach to treating the skin," the researchers highlighted numerous existing or emerging applications for the technology, outlined below.

Skin rejuvenation

Many modalities developed to reverse the dermal and epidermal signs of photoaging and chronological aging depend on the removal of the epidermis and the induction of a controlled form of skin wounding to promote collagen biosynthesis and dermal matrix remodeling. Examples include retinoic acid, dermabrasion, chemical peels, and ablative laser resurfacing.

These modalities require intensive posttreatment care and prolonged down time, and are associated with a risk of numerous complications, the researchers said.

LLLT represents an alternative that is known to increase microcirculation and vascular perfusion in the skin. Data from previous studies have shown that LLLT increased collagen and improved wrinkles and skin laxity with less down time and risk than that of other treatments.

In one study, for example, 300 patients treated with only a light-emitting diode (LED) LLLT device set at 590 nm, 0.10 J/cm², were compared with 600 patients who received the LED therapy in combination with a thermal-based photorejuvenation procedure. Of those who received LED therapy alone, 90% reported softer skin and less roughness and fine lines. The changes ranged from subtle to significant.

Those who received thermal photorejuvenation laser treatment reported a reduction in posttreatment erythema and an overall impression of increased efficacy with the additional LED treatment – an effect that could be attributed to anti-inflammatory effects of LLLT, they noted.

In another study, more than 90% of 90 patients receiving eight LED treatments over 4 weeks experienced favorable results, improving by at least one Fitzpatrick photoaging category. In addition, 65% of patients experienced global improvement in facial texture, fine lines, background erythema, and pigmentation, with results peaking 4-6 months after completion.

Acne treatment

LLLT in the red to near-infrared (NIR) spectral range (630-1000 nm) and with nonthermal power (less than 200 mW) has been shown in several studies to improve acne vulgaris. In one study, a significant reduction in active acne lesions occurred after 12 twice-weekly sessions using 630 nm red-spectrum LLLT with a fluence of 12 J/cm² in conjunction with 2% topical clindamycin. No significant effects were seen using an 890-nm laser. Other studies have demonstrated that the combination of blue and red light is synergistic for treating acne.

Photoprotection

Recent suggestions that infrared exposure might have protective effects against ultraviolet light–induced skin damage are based on the theory that the exposure might trigger protective or repair responses to UV irradiation. While controversial, this view is supported by data suggesting potential mechanisms of action. For example, some data suggest a role of p53, a sensor of gene integrity involved in cell apoptosis and repair mechanisms. In one study, the response to infrared (IR) irradiation was shown to be p53 dependent, suggesting the IR irradiation prepares cells to resist and/or repair further UV-induced DNA damage. Data from another study showed that IR irradiation induced the protective protein ferritin, which is involved in skin repair.

Data from yet another study suggested that nerve growth factor (NGF) production induced by LLLT using the helium neon semiconductor laser diode (HeNe, 633 nm) might explain the photoprotective effects of LLLT. In that study, NGF – a major paracrine maintenance factor for melanocyte survival in skin, was shown to protect melanocytes from UV-induced apoptosis by upregulating the level of Bcl-2 (an antiapoptotic protein) in the cells.

Herpesvirus lesion treatment

New therapies are needed to shorten recurrent herpesvirus episodes and reduce related pain and inflammation. LLLT has been suggested as an alternative to current medications. In one study of 50 patients with recurrent perioral HSV infection, LLLT at 690 nm, 80 mW/cm², 48 J/cm² daily for 2 weeks during recurrence-free periods decreased the frequency of herpes labialis episodes, the authors said.

In another study with similar parameters, patients achieved a significant prolongation of remission intervals from 30 to 73 days.

The mechanism of action remains unclear, but an indirect effect of LLLT on cellular and humoral components of the immune system may be involved in antiviral responses, as opposed to a direct virus-inactivating effect, the researchers noted.

Vitiligo treatment

Modest efficacy seen with the low-energy HeNe laser (632 nm, 25 mW/cm²) for the treatment of 18 vitiligo patients led to speculation that LLLT could serve as an alternative effective treatment for this typically treatment-resistant condition. (Repigmentation was observed in 64%, and some follicular repigmentation was observed in the remaining patients).

In a subsequent study of local administration of the HeNe laser light at 3 J/cm², 1.0 mW, 632.8 nm in patients with segmental type vitiligo, marked perilesional and perifollicular repigmentation of more than 50% was observed in 60% of patients.

"Both NGF and (basic fibroblast growth factor) stimulate melanocyte migration, and deficiencies of these mediators may participate in the development of vitiligo," the researchers wrote.

Depigmentation

During tests of red and blue light for acne, researchers unexpectedly found that patients treated with both red and blue light experienced an overall decrease in melanin.

Based on instrumental measurement results, blue light exposure (415 nm, 40 mW/cm², 48 J/cm²), increased the melanin level by 6.7, whereas red light exposure (633 nm, 80 mW/cm², 96 J/cm²) decreased the melanin level by 15.5.

"This finding may have some relationship with the laser’s brightening effect of the skin tone, which 14 of 24 patients spontaneously reported after the treatment period. However, as of today, no other studies investigated or reported a similar decrease in melanin levels after red light irradiations," the researchers said.

Hypertrophic scar and keloid eradication

LLLT has shown promise for preventing hypertrophic and keloid scars in patients who undergo scar revision by surgery or CO₂ laser. The use of daily near-infrared LED (NIR-LED) treatment on one of the two bilateral sites safely reduced the risk of scar development in that lesion, compared with the untreated lesion in three patients with bilateral scars. One underwent surgical revision/excision for preauricular linear keloids that developed after a face-lift procedure, one underwent CO₂ resurfacing for hypertrophic acne scars on the chest, and one underwent CO₂ resurfacing after excision of hypertrophic scars on the back. No significant treatment-related adverse effects were reported.

LLLT may work in these types of scars through an inhibitory effect on interleukin-6 mRNA levels and the modulating of platelet derived growth factor, transforming growth factor–beta, interleukins, and MMPs, which are associated with abnormal wound healing, the researchers noted.

Burn treatment

LED exposure was shown to provide benefit for the treatment of acute sunburn in a study of 10 patients.

Treatment once or twice daily for 3 days on half of the affected area decreased symptoms of burning, redness, swelling, and peeling compared with the untreated half. Decreased MMP-1 was noted on the treated side through immunofluorescence staining in one patient, and real-time polymerase chain reaction gene expression analysis showed a significant decrease in MMP-1 gene expression at both 4 and 24 hours after the UV injury on the treated side.

In another study, LED treatment was effective compared with control for speeding the healing process of laser treatment–related burns. In nine patients with second-degree burns from nonablative laser devices, LED therapy once daily for 1 week was associated with 50% faster healing based on both patient and physician accounts.

LED treatment also was shown in a pilot study to accelerate re-epithelialization of a forearm injury induced by a CO₂ laser; identical test sites were treated with daily dressing changes and polysporin ointment, but the site with faster re-epithelialization had also received the LED treatment (a computer pattern generator was used to deliver the identical CO₂ treatment to both sites).

Psoriasis

LLLT also shows promise for the treatment of plaque psoriasis. In a preliminary study, the combined use of sequential NIR (830 nm) and visible red light (630 nm) led to resolution of psoriasis in patients who were resistant to conventional therapy. The patients received treatment in two 20-minute sessions, 48 hours apart, for 4 or 5 weeks. No adverse side effects occurred.

Despite the variety of potential applications for the technology, LLLT remains somewhat controversial due to "uncertainties about the fundamental molecular and cellular mechanisms responsible for transducing signals from the photons incident on the cells to the biological effects that take place in the irradiated tissue" and because "there are significant variations in terms of dosimetry parameter: wavelength, irradiance or power density, pulse structure, coherence, polarization, energy, fluence, irradiation time, contact versus noncontact application, and repetition regimen," the researchers said.

They noted, however, that problems that have been experienced with LLLT – as well as negative study results – could be the result of inappropriate parameters, skin preparation, and/or device maintenance.

"LLLT appears to have a wide range of applications in dermatology, especially in indications where stimulation of healing, reduction of inflammation, reduction of cell death, and skin rejuvenation are required," they noted, but added that the lack of agreement on important parameters (particularly whether red, NIR, or a combination of both is optimal for a given application) has created a credibility gap that must be overcome before LLLT is routinely applied in every dermatologist’s office.

Once LLLT does become so widely accepted, however, it may be time for dermatologists to move on to the next big thing, Dr. Alam said in his article on the future of procedural dermatology.

"For several decades, dermatologists have worked closely with start-up companies to commercialize new devices and technologies ... when new toxins, fillers, and energy devices have been marketed, dermatologists have been early adopters," he said. "Over time, each device or procedure has diminished in cost and exclusivity as other physicians and nonphysicians have entered the market, and dermatologists have moved on to greener pastures. In all likelihood, this cycle will continue," he noted. "Dermatologists cannot prevent the dissemination of stable technologies, but they can continue to innovate and create new ones."

In fact, he added, continued success in this arena will rest largely on clinicians’ ability to nurture innovation to ensure a healthy pipeline of novel technologies.

The authors of the articles had no financial conflicts to disclose.

Noninvasive procedural dermatology has evolved at a dizzying pace, and continues to do so.

In addition to an array of procedures for skin tightening, skin resurfacing, and fat reduction, emerging technologies such as complex feedback devices, nanotechnology, and stem cell–based therapies promise to keep dermatology at the forefront of the cosmetic and esthetic realm, according to Dr. Murad Alam.

In an article featured in the March issue of Seminars in Cutaneous Medicine and Surgery, Dr. Alam of Northwestern University, Chicago, makes several predictions about the future of these technologies (Semin. Cutan. Med. Surg. 2013;32:61-63).

For example, like modern vehicles equipped with computer chips that can change steering and braking in response to environmental conditions, dermatologic devices will soon include technology that uses precise feedback to make automated setting changes, he said.

"Over time, the reduced cost of microelectronics, feedback controls, and computing power is simplifying the capacity of devices to analyze intraoperative information and adjust the procedure to compensate. For instance, certain laser and energy devices already have tips that are able to sense the temperature in the microenvironment and adjust power output to maintain site-specific temperature within a narrow band," he explained.

This technology could increase effectiveness and improve the safety of devices by reducing the level of operator time and expertise needed, and by making setting changes faster than humanly possible.

Autonomous nanotechnology devices are another advance described by Dr. Alam.

Miniaturization will become more feasible and affordable, and eventually devices will become "so exceedingly small that they will be mostly disposable and deployed in large numbers to the treatment site," he said.

The concept of hundreds of minuscule machines deployed to resurface skin or repair a wound may sound like science fiction, but the rapid advances in nanotechnology could make it a reality that could lead to the creation of new procedures such as ways to treat scars that can’t be corrected using currently available technologies, he added.

Dr. Alam’s other predictions for the future of noninvasive procedural dermatology included:

• Optimization of minimally invasive procedures for fat reduction and skin tightening, which currently provide only mild to modest results and longevity.

• The use of stem cells for augmentation of tissue layers, which could provide genuine rejuvenation rather than simply repair and concealment.

• The improvement of artificial dermal substitutes that can develop many of the functions of live skin, and can be grafted without inducing contractures.

• The development of rapid treatments for pigmentation using nanotechnology and cellular therapies, which will allow for precise melanocyte and melanosome transfer and automatic recoloration of discolored skin.

While these technologies continue to emerge, plenty of others have already established their places in the dermatology arena. The many and varied applications of one of these – low-level laser therapy, or LLLT – are described in another article in the March issue of Seminars in Cutaneous Medicine and Surgery (Semin. Cutan. Med. Surg. 2013;32:42-54).

"LLLT involves exposing cells or tissue to low levels of red and near-infrared light. ... Recently, medical treatment with LLLT at various intensities has been found to stimulate or inhibit an assortment of cellular processes," wrote Dr. Pinar Avci of Massachusetts General Hospital, Boston, and his colleagues, noting that the mechanism associated with the cellular photobiostimulation by LLLT is not yet fully understood, but appears to have a wide range of effects at the molecular, cellular, and tissue levels.

Describing LLLT as "possibly the ultimate noninvasive approach to treating the skin," the researchers highlighted numerous existing or emerging applications for the technology, outlined below.

Skin rejuvenation

Many modalities developed to reverse the dermal and epidermal signs of photoaging and chronological aging depend on the removal of the epidermis and the induction of a controlled form of skin wounding to promote collagen biosynthesis and dermal matrix remodeling. Examples include retinoic acid, dermabrasion, chemical peels, and ablative laser resurfacing.

These modalities require intensive posttreatment care and prolonged down time, and are associated with a risk of numerous complications, the researchers said.

LLLT represents an alternative that is known to increase microcirculation and vascular perfusion in the skin. Data from previous studies have shown that LLLT increased collagen and improved wrinkles and skin laxity with less down time and risk than that of other treatments.

In one study, for example, 300 patients treated with only a light-emitting diode (LED) LLLT device set at 590 nm, 0.10 J/cm², were compared with 600 patients who received the LED therapy in combination with a thermal-based photorejuvenation procedure. Of those who received LED therapy alone, 90% reported softer skin and less roughness and fine lines. The changes ranged from subtle to significant.

Those who received thermal photorejuvenation laser treatment reported a reduction in posttreatment erythema and an overall impression of increased efficacy with the additional LED treatment – an effect that could be attributed to anti-inflammatory effects of LLLT, they noted.

In another study, more than 90% of 90 patients receiving eight LED treatments over 4 weeks experienced favorable results, improving by at least one Fitzpatrick photoaging category. In addition, 65% of patients experienced global improvement in facial texture, fine lines, background erythema, and pigmentation, with results peaking 4-6 months after completion.

Acne treatment

LLLT in the red to near-infrared (NIR) spectral range (630-1000 nm) and with nonthermal power (less than 200 mW) has been shown in several studies to improve acne vulgaris. In one study, a significant reduction in active acne lesions occurred after 12 twice-weekly sessions using 630 nm red-spectrum LLLT with a fluence of 12 J/cm² in conjunction with 2% topical clindamycin. No significant effects were seen using an 890-nm laser. Other studies have demonstrated that the combination of blue and red light is synergistic for treating acne.

Photoprotection

Recent suggestions that infrared exposure might have protective effects against ultraviolet light–induced skin damage are based on the theory that the exposure might trigger protective or repair responses to UV irradiation. While controversial, this view is supported by data suggesting potential mechanisms of action. For example, some data suggest a role of p53, a sensor of gene integrity involved in cell apoptosis and repair mechanisms. In one study, the response to infrared (IR) irradiation was shown to be p53 dependent, suggesting the IR irradiation prepares cells to resist and/or repair further UV-induced DNA damage. Data from another study showed that IR irradiation induced the protective protein ferritin, which is involved in skin repair.

Data from yet another study suggested that nerve growth factor (NGF) production induced by LLLT using the helium neon semiconductor laser diode (HeNe, 633 nm) might explain the photoprotective effects of LLLT. In that study, NGF – a major paracrine maintenance factor for melanocyte survival in skin, was shown to protect melanocytes from UV-induced apoptosis by upregulating the level of Bcl-2 (an antiapoptotic protein) in the cells.

Herpesvirus lesion treatment

New therapies are needed to shorten recurrent herpesvirus episodes and reduce related pain and inflammation. LLLT has been suggested as an alternative to current medications. In one study of 50 patients with recurrent perioral HSV infection, LLLT at 690 nm, 80 mW/cm², 48 J/cm² daily for 2 weeks during recurrence-free periods decreased the frequency of herpes labialis episodes, the authors said.

In another study with similar parameters, patients achieved a significant prolongation of remission intervals from 30 to 73 days.

The mechanism of action remains unclear, but an indirect effect of LLLT on cellular and humoral components of the immune system may be involved in antiviral responses, as opposed to a direct virus-inactivating effect, the researchers noted.

Vitiligo treatment

Modest efficacy seen with the low-energy HeNe laser (632 nm, 25 mW/cm²) for the treatment of 18 vitiligo patients led to speculation that LLLT could serve as an alternative effective treatment for this typically treatment-resistant condition. (Repigmentation was observed in 64%, and some follicular repigmentation was observed in the remaining patients).

In a subsequent study of local administration of the HeNe laser light at 3 J/cm², 1.0 mW, 632.8 nm in patients with segmental type vitiligo, marked perilesional and perifollicular repigmentation of more than 50% was observed in 60% of patients.

"Both NGF and (basic fibroblast growth factor) stimulate melanocyte migration, and deficiencies of these mediators may participate in the development of vitiligo," the researchers wrote.

Depigmentation

During tests of red and blue light for acne, researchers unexpectedly found that patients treated with both red and blue light experienced an overall decrease in melanin.

Based on instrumental measurement results, blue light exposure (415 nm, 40 mW/cm², 48 J/cm²), increased the melanin level by 6.7, whereas red light exposure (633 nm, 80 mW/cm², 96 J/cm²) decreased the melanin level by 15.5.

"This finding may have some relationship with the laser’s brightening effect of the skin tone, which 14 of 24 patients spontaneously reported after the treatment period. However, as of today, no other studies investigated or reported a similar decrease in melanin levels after red light irradiations," the researchers said.

Hypertrophic scar and keloid eradication

LLLT has shown promise for preventing hypertrophic and keloid scars in patients who undergo scar revision by surgery or CO₂ laser. The use of daily near-infrared LED (NIR-LED) treatment on one of the two bilateral sites safely reduced the risk of scar development in that lesion, compared with the untreated lesion in three patients with bilateral scars. One underwent surgical revision/excision for preauricular linear keloids that developed after a face-lift procedure, one underwent CO₂ resurfacing for hypertrophic acne scars on the chest, and one underwent CO₂ resurfacing after excision of hypertrophic scars on the back. No significant treatment-related adverse effects were reported.

LLLT may work in these types of scars through an inhibitory effect on interleukin-6 mRNA levels and the modulating of platelet derived growth factor, transforming growth factor–beta, interleukins, and MMPs, which are associated with abnormal wound healing, the researchers noted.

Burn treatment

LED exposure was shown to provide benefit for the treatment of acute sunburn in a study of 10 patients.

Treatment once or twice daily for 3 days on half of the affected area decreased symptoms of burning, redness, swelling, and peeling compared with the untreated half. Decreased MMP-1 was noted on the treated side through immunofluorescence staining in one patient, and real-time polymerase chain reaction gene expression analysis showed a significant decrease in MMP-1 gene expression at both 4 and 24 hours after the UV injury on the treated side.

In another study, LED treatment was effective compared with control for speeding the healing process of laser treatment–related burns. In nine patients with second-degree burns from nonablative laser devices, LED therapy once daily for 1 week was associated with 50% faster healing based on both patient and physician accounts.

LED treatment also was shown in a pilot study to accelerate re-epithelialization of a forearm injury induced by a CO₂ laser; identical test sites were treated with daily dressing changes and polysporin ointment, but the site with faster re-epithelialization had also received the LED treatment (a computer pattern generator was used to deliver the identical CO₂ treatment to both sites).

Psoriasis

LLLT also shows promise for the treatment of plaque psoriasis. In a preliminary study, the combined use of sequential NIR (830 nm) and visible red light (630 nm) led to resolution of psoriasis in patients who were resistant to conventional therapy. The patients received treatment in two 20-minute sessions, 48 hours apart, for 4 or 5 weeks. No adverse side effects occurred.

Despite the variety of potential applications for the technology, LLLT remains somewhat controversial due to "uncertainties about the fundamental molecular and cellular mechanisms responsible for transducing signals from the photons incident on the cells to the biological effects that take place in the irradiated tissue" and because "there are significant variations in terms of dosimetry parameter: wavelength, irradiance or power density, pulse structure, coherence, polarization, energy, fluence, irradiation time, contact versus noncontact application, and repetition regimen," the researchers said.

They noted, however, that problems that have been experienced with LLLT – as well as negative study results – could be the result of inappropriate parameters, skin preparation, and/or device maintenance.

"LLLT appears to have a wide range of applications in dermatology, especially in indications where stimulation of healing, reduction of inflammation, reduction of cell death, and skin rejuvenation are required," they noted, but added that the lack of agreement on important parameters (particularly whether red, NIR, or a combination of both is optimal for a given application) has created a credibility gap that must be overcome before LLLT is routinely applied in every dermatologist’s office.

Once LLLT does become so widely accepted, however, it may be time for dermatologists to move on to the next big thing, Dr. Alam said in his article on the future of procedural dermatology.

"For several decades, dermatologists have worked closely with start-up companies to commercialize new devices and technologies ... when new toxins, fillers, and energy devices have been marketed, dermatologists have been early adopters," he said. "Over time, each device or procedure has diminished in cost and exclusivity as other physicians and nonphysicians have entered the market, and dermatologists have moved on to greener pastures. In all likelihood, this cycle will continue," he noted. "Dermatologists cannot prevent the dissemination of stable technologies, but they can continue to innovate and create new ones."

In fact, he added, continued success in this arena will rest largely on clinicians’ ability to nurture innovation to ensure a healthy pipeline of novel technologies.

The authors of the articles had no financial conflicts to disclose.

Community Oncology's podcasts by Editor in Chief Dr. David Henry features an update on vismodegib for advanced basal cell carcinoma and a rapid desensitization regimen for patients with hypersensitivity reactions to platinum compounds and taxanes.

Community Oncology's podcasts by Editor in Chief Dr. David Henry features an update on vismodegib for advanced basal cell carcinoma and a rapid desensitization regimen for patients with hypersensitivity reactions to platinum compounds and taxanes.

Community Oncology's podcasts by Editor in Chief Dr. David Henry features an update on vismodegib for advanced basal cell carcinoma and a rapid desensitization regimen for patients with hypersensitivity reactions to platinum compounds and taxanes.

Vismodegib is an oral small-molecule inhibitor of smoothened homologue protein (SMO), a component of the hedgehog signaling pathway that has been shown to have activity in advanced basal cell carcinoma (BCC). In early 2012, vismodegib was approved by the Food and Drug Administration for treatment of adult patients with metastatic BCC (mBCC) who are not candidates for radiation therapy and adult patients with locally advanced BCC that has recurred following surgery or who are not candidates for surgery or radiation therapy1…

*Click on the links to the left of this introduction for a PDF of the full article and an accompanying Commentary.

Vismodegib is an oral small-molecule inhibitor of smoothened homologue protein (SMO), a component of the hedgehog signaling pathway that has been shown to have activity in advanced basal cell carcinoma (BCC). In early 2012, vismodegib was approved by the Food and Drug Administration for treatment of adult patients with metastatic BCC (mBCC) who are not candidates for radiation therapy and adult patients with locally advanced BCC that has recurred following surgery or who are not candidates for surgery or radiation therapy1…

*Click on the links to the left of this introduction for a PDF of the full article and an accompanying Commentary.

Vismodegib is an oral small-molecule inhibitor of smoothened homologue protein (SMO), a component of the hedgehog signaling pathway that has been shown to have activity in advanced basal cell carcinoma (BCC). In early 2012, vismodegib was approved by the Food and Drug Administration for treatment of adult patients with metastatic BCC (mBCC) who are not candidates for radiation therapy and adult patients with locally advanced BCC that has recurred following surgery or who are not candidates for surgery or radiation therapy1…

*Click on the links to the left of this introduction for a PDF of the full article and an accompanying Commentary.