In cutaneous field cancerization, focal treatments such as cryotherapy are impractical, thus necessitating the use of field-directed therapies over the lesion and the surrounding skin field. Although evidence-based guidelines do not exist, field-directed therapy has been proposed in cases of 3 or more actinic keratoses (AKs) in a 25-cm² area or larger.¹ It can be further speculated that patients who are vulnerable to aggressive phenotypes of cutaneous malignancies, such as those with a genodermatosis or who are immunocompromised, necessitate a higher index of suspicion for field effect with even 1 or 2 AKs.

Current field-directed therapies include topical agents (imiquimod, fluorouracil, ingenol mebutate, and diclo-fenac), photodynamic therapy (PDT), and resurfacing procedures (lasers, chemical peels, dermabrasion). Although topical agents and PDT currently are gold standards in field treatment, the use of energy-based devices (ie, ablative and nonablative lasers) are attractive options as monotherapy or as part of a combination therapy. These devices are attractive options for field-directed therapy because they offer defined, customizable control of settings, allowing for optimal cosmesis and precision of therapy.

Principally, lasers function by damaging skin tissue to induce resurfacing, neocollagenesis, and vascular restructuring. Fractional versions of ablative and nonablative systems are available to target a fraction of the treatment area in evenly spaced microthermal zones and to minimize overall thermal damage.²

Given recent advances in laser systems and numerous investigations reported in the literature, a review of ablative and nonablative lasers that have been studied as treatment options for cutaneous field cancerization is provided, with a focus on treatment efficacy.

Ablative Lasers

Ablative lasers operate at higher wavelengths than nonablative lasers to destroy epidermal and dermal tissue. The 10,600-nm carbon dioxide (CO₂) and 2940-nm Er:YAG lasers have been heavily investigated for field therapy for multiple AKs, both as monotherapies (Table 1) and in combination with PDT (Table 2).

Monotherapy
One randomized trial with 5-year follow-up compared the efficacy of full-face pulsed CO₂ laser therapy, full-face trichloroacetic acid (TCA) peel 30%, and fluorouracil cream 5% (twice daily for 3 weeks) on AKs on the face and head.³ Thirty-one participants were randomized to the 3 treatment arms and a negative control arm. The mean AK counts at baseline for the CO₂, TCA, and fluorouracil treatment groups were 78.0, 83.7, and 61.8, respectively. At 3-month follow-up, all treatment groups had significant reductions in the mean AK count from baseline (CO₂ group, 92% [P=.03]; TCA group, 89% [P=.004]; fluorouracil group, 83% [P=.008]). No significant differences in efficacy among the treatment groups were noted. All 3 treatment groups had a demonstrably lower incidence of nonmelanoma skin cancer over 5-year follow-up compared to the control group (P<.001).³

In contrast to these promising results, the pulsed CO₂ laser showed only short-term efficacy in a split-face study of 12 participants with at least 5 facial or scalp AKs on each of 2 symmetric facial sides who were randomized to 1 treatment side.⁴ At 1-month follow-up, the treatment side exhibited significantly fewer AKs compared to the control side (47% vs 71% at baseline; P=.01), but the improvement was not sustained at 3-month follow-up (49% vs 57%; P=.47).⁴

In another study, the CO₂ laser was found to be inferior to 5-aminolevulinic acid PDT.⁵ Twenty-one participants who had at least 4 AKs in each symmetric half of a body region (head, hands, forearms) were randomized to PDT on 1 side and CO₂ laser therapy on the other. Median baseline AK counts for the PDT and CO₂ laser groups were 6 and 8, respectively. Both treatment groups exhibited significant median AK reduction from baseline 4 weeks posttreatment (PDT group, 82.1% [P<.05], CO₂ laser group, 100% [P<.05]); however. at 3 months posttreatment the PDT group had significantly higher absolute (P=.0155) and relative (P=.0362) reductions in AK count compared to the CO₂ laser group. One participant received a topical antibiotic for superficial infection on the PDT treatment side.⁵

Many questions remain regarding the practical application of laser ablation monotherapy for multiple AKs. More studies are needed to determine the practicality and long-term clinical efficacy of these devices.

PDT Combination Therapy
Laser ablation may be combined with PDT to increase efficacy and prolong remission rates. In fact, laser ablation may be thought of as a physical drug-delivery system to boost uptake of topical agents—in this case, aminolevulinic acid and methyl aminolevulinate (MAL)—given that it disrupts the skin barrier.

In a comparative study of ablative fractional laser (AFXL)–assisted PDT and AFXL alone in 10 organ transplant recipients on immunosuppression with at least 5 AKs on each dorsal hand, participants were randomized to AFXL-PDT on one treatment side and PDT on the other side.⁶ Participants received AFXL in an initial lesion-directed pass and then a second field-directed pass of a fractional CO₂ laser. After AFXL exposure, methyl aminolevulinate was applied to the AFXL-PDT treatment side, with 3-hour occlusion. A total of 680 AKs were treated (335 in the AFXL-PDT group, 345 in the PDT group); results were stratified by the clinical grade of the lesion (1, slightly palpable; 2, moderately thick; 3, very thick or obvious). At 4-month follow-up, the AFXL-PDT group had a significantly higher median complete response rate of 73% compared to 31% in the AFXL group (P=.002). Interestingly, AFXL-PDT was also significantly more efficacious compared to AFXL for grades 1 (80% vs 37%; P=.02) and 2 (53% vs 7%, P=.009) AKs but not grade 3 AKs (4% vs 0%, P=.17).⁶

The combination of fractional CO₂ laser and PDT also demonstrated superiority to PDT.⁷ In a split-face investigation, 15 participants with bilateral symmetric areas of 2 to 10 AKs on the face or scalp were randomized to receive fractional CO₂ laser and MAL-PDT combination therapy on 1 treatment side and conventional MAL-PDT on the other side.⁷ The AFXL-PDT treatment side received laser ablation with immediate subsequent application of MAL to both treatment sides under 3-hour occlusion. At baseline, 103 AKs were treated by AFXL-PDT and 109 AKs were treated with conventional PDT. At 3-month follow-up, the AFXL-PDT treatment group exhibited a significantly higher rate of complete response (90%) compared to the conventional PDT group (67%)(P=.0002).⁷

Like the CO₂ laser, the Er:YAG laser has demonstrated superior results when used in combination with PDT to treat field cancerization compared to either treatment alone. In a comparison study, 93 patients with 2 to 10 AK lesions on the face or scalp were randomized to treatment with AFXL (Er:YAG laser) and MAL-PDT with 3-hour occlusion, AFXL (Er:YAG laser) and MAL-PDT with 2-hour occlusion, and MAL-PDT with 3-hour occlusion.⁸ A total of 440 baseline AK lesions on the face or scalp were treated. At 3-month follow-up, the AFXL-PDT (3-hour occlusion) group had the highest rate of complete response (91.7%), compared to 76.8% (P=.001) in the AFXL-PDT (2-hour occlusion) and 65.6% (P=.001) in the PDT groups, regardless of the grade of AK lesion. The AFXL-PDT (2-hour occlusion) treatment was also superior to PDT alone (P=.038). These findings were sustained at 12-month follow-up (84.8% in the AFXL-PDT [3-hour occlusion] group [P<.001, compared to others]; 67.5% in the AFXL-PDT [2-hour occlusion] group [P<.001, compared to 3-hour PDT]; 51.1% in the PDT group). Importantly, the AK lesion recurrence rate was also lowest in the AFL-PDT (3-hour occlusion) group (7.5% vs 12.1% and 22.1% in the AFXL-PDT [2-hour occlusion] and PDT groups, respectively; P=.007).⁸

Combination therapy with AFXL and daylight PDT (dPDT) may improve the tolerability of PDT and the efficacy rate of field therapy in organ transplant recipients. One study demonstrated the superiority of this combination therapy in a population of 16 organ transplant recipients on immunosuppressants with at least 2 moderate to severely thick AKs in each of 4 comparable areas in the same anatomic region.⁹ The 4 areas were randomized to a single session of AFXL-dPDT, dPDT alone, conventional PDT, or AFXL alone. Ablation was performed with a fractional Er:YAG laser. The AFXL-dPDT and dPDT alone groups received MAL for 2.5 hours without occlusion, and the conventional PDT group received MAL for 3 hours with occlusion. Daylight exposure in dPDT groups was initiated 30 minutes after MAL application for 2 hours total. A baseline total of 542 AKs were treated. At 3-month follow-up, the complete response rate was highest for the AFXL-dPDT group (74%) compared to dPDT alone (46%; P=.0262), conventional PDT (50%; P=.042), and AFXL alone (5%; P=.004). Pain scores for AFXL–dPDT and dPDT alone were significantly lower than for conventional PDT and AFXL alone (P<.001).⁹

Nonablative Lasers

By heating the dermis to induce neogenesis without destruction, nonablative lasers offer superior healing times compared to their ablative counterparts. Multiple treatments with nonablative lasers may be necessary for maximal effect. Four nonablative laser devices have demonstrated efficacy in the treatment of multiple AKs^10-14: (1) the Q-switched 1064-nm Nd:YAG laser, with or without a 532-nm potassium titanyl phosphate (KTP) laser; (2) the 1540-nm fractional erbium glass laser; (3) the 1550-nm fractional erbium-doped fiber laser; and (4) the 1927-nm fractional thulium laser (Table 3).

In a proof-of-concept study of the Q-switched Nd:YAG laser with the 532-nm KTP laser, 1 treatment session induced full remission of AKs in 10 patients at follow-up day 20, although the investigator did not grade improvement on a numerical scale.¹⁰ In a study of the fractional Q-switched 1064-nm Nd:YAG laser alone, 6 patients with trace or mild AKs received 4 treatment sessions at approximately 2-week intervals.¹⁴ All but 1 patient (who had trace AKs) had no AKs at 3-month follow-up.

The efficacy of the 1540-nm fractional erbium glass laser was examined in 17 participants with investigator-rated moderate-to-severe AK involvement of the scalp and face.¹² Participants were given 2 or 3 treatment sessions at 3- to 4-week intervals and were graded by blinded dermatologists on a quartile scale of 0 (no improvement), 1 (1%–25% improvement), 2 (26%–50% improvement), 3 (51%–75% improvement), or 4 (76%–100% improvement). At 3 months posttreatment, the average grade of improvement was 3.4.¹²

The 1550-nm fractional erbium-doped fiber laser was tested in 14 men with multiple facial AKs (range, 9–44 AKs [mean, 22.1 AKs]).¹¹ Participants received 5 treatment sessions at 2- to 4-week intervals, with majority energies used at 70 MJ and treatment level 11. The mean AK count was reduced significantly by 73.1%, 66.2%, and 55.6% at 1-, 3-, and 6-month follow-up, respectively (P<.001).¹¹

The 1927-nm fractional thulium laser showed promising results in 24 participants with facial AKs.¹³ Participants received up to 4 treatment sessions at intervals from 2 to 6 weeks at the investigators’ discretion. At baseline, patients had an average of 14.04 facial AKs. At 1-, 3-, and 6-month follow-up, participants exhibited 91.3%, 87.3%, and 86.6% reduction in AK counts, respectively. The mean AK count at 3-month follow-up was 1.88.¹³

Due to limited sample sizes and/or lack of quantifiable results and controls in these studies, more studies are needed to fully elucidate the role of nonablative lasers in the treatment of AK.

Future Directions

Iontophoresis involves the noninvasive induction of an electrical current to facilitate ion movement through the skin and may be a novel method to boost the efficacy of current field therapies. In the first known study of its kisnd, iontophoresis-assisted AFXL-PDT was found to be noninferior to conventional AFXL-PDT¹⁵; however, additional studies demonstrating its superiority are needed before more widespread clinical use is considered.

Pretreatment with AFXL prior to topical field-directed therapies also has been proposed.¹⁶ In a case series of 13 patients, combination therapy with AFXL and ingenol mebutate was shown to be superior to ingenol mebutate alone (AK clearance rate, 89.2% vs 72.1%, respectively; P<.001).¹⁶ Randomized studies with longer follow-up time are needed.

Conclusion

Ablative and nonablative laser systems have yielded limited data about their potential as monotherapies for treatment of multiple AKs and are unlikely to replace topical agents and PDT as a first-line modality in field-directed treatment at this time. More studies with a larger number of participants and long-term follow-up are needed for further clarification of efficacy, safety, and clinical feasibility. Nevertheless, fractional ablative lasers in combination with PDT have shown robust efficacy and a favorable safety profile for treatment of multiple AKs.^6-9 Further, this combination therapy exhibited a superior clearance rate and lower lesion recurrence in organ transplant recipients—a demographic that classically is difficult to treat.^6-9

With continued rapid evolution of laser systems and more widespread use in dermatology, monotherapy and combination therapy may offer a dynamic new option in field cancerization that can decrease disease burden and treatment frequency.

In cutaneous field cancerization, focal treatments such as cryotherapy are impractical, thus necessitating the use of field-directed therapies over the lesion and the surrounding skin field. Although evidence-based guidelines do not exist, field-directed therapy has been proposed in cases of 3 or more actinic keratoses (AKs) in a 25-cm² area or larger.¹ It can be further speculated that patients who are vulnerable to aggressive phenotypes of cutaneous malignancies, such as those with a genodermatosis or who are immunocompromised, necessitate a higher index of suspicion for field effect with even 1 or 2 AKs.

Current field-directed therapies include topical agents (imiquimod, fluorouracil, ingenol mebutate, and diclo-fenac), photodynamic therapy (PDT), and resurfacing procedures (lasers, chemical peels, dermabrasion). Although topical agents and PDT currently are gold standards in field treatment, the use of energy-based devices (ie, ablative and nonablative lasers) are attractive options as monotherapy or as part of a combination therapy. These devices are attractive options for field-directed therapy because they offer defined, customizable control of settings, allowing for optimal cosmesis and precision of therapy.

Principally, lasers function by damaging skin tissue to induce resurfacing, neocollagenesis, and vascular restructuring. Fractional versions of ablative and nonablative systems are available to target a fraction of the treatment area in evenly spaced microthermal zones and to minimize overall thermal damage.²

Given recent advances in laser systems and numerous investigations reported in the literature, a review of ablative and nonablative lasers that have been studied as treatment options for cutaneous field cancerization is provided, with a focus on treatment efficacy.

Ablative Lasers

Ablative lasers operate at higher wavelengths than nonablative lasers to destroy epidermal and dermal tissue. The 10,600-nm carbon dioxide (CO₂) and 2940-nm Er:YAG lasers have been heavily investigated for field therapy for multiple AKs, both as monotherapies (Table 1) and in combination with PDT (Table 2).

Monotherapy
One randomized trial with 5-year follow-up compared the efficacy of full-face pulsed CO₂ laser therapy, full-face trichloroacetic acid (TCA) peel 30%, and fluorouracil cream 5% (twice daily for 3 weeks) on AKs on the face and head.³ Thirty-one participants were randomized to the 3 treatment arms and a negative control arm. The mean AK counts at baseline for the CO₂, TCA, and fluorouracil treatment groups were 78.0, 83.7, and 61.8, respectively. At 3-month follow-up, all treatment groups had significant reductions in the mean AK count from baseline (CO₂ group, 92% [P=.03]; TCA group, 89% [P=.004]; fluorouracil group, 83% [P=.008]). No significant differences in efficacy among the treatment groups were noted. All 3 treatment groups had a demonstrably lower incidence of nonmelanoma skin cancer over 5-year follow-up compared to the control group (P<.001).³

In contrast to these promising results, the pulsed CO₂ laser showed only short-term efficacy in a split-face study of 12 participants with at least 5 facial or scalp AKs on each of 2 symmetric facial sides who were randomized to 1 treatment side.⁴ At 1-month follow-up, the treatment side exhibited significantly fewer AKs compared to the control side (47% vs 71% at baseline; P=.01), but the improvement was not sustained at 3-month follow-up (49% vs 57%; P=.47).⁴

In another study, the CO₂ laser was found to be inferior to 5-aminolevulinic acid PDT.⁵ Twenty-one participants who had at least 4 AKs in each symmetric half of a body region (head, hands, forearms) were randomized to PDT on 1 side and CO₂ laser therapy on the other. Median baseline AK counts for the PDT and CO₂ laser groups were 6 and 8, respectively. Both treatment groups exhibited significant median AK reduction from baseline 4 weeks posttreatment (PDT group, 82.1% [P<.05], CO₂ laser group, 100% [P<.05]); however. at 3 months posttreatment the PDT group had significantly higher absolute (P=.0155) and relative (P=.0362) reductions in AK count compared to the CO₂ laser group. One participant received a topical antibiotic for superficial infection on the PDT treatment side.⁵

Many questions remain regarding the practical application of laser ablation monotherapy for multiple AKs. More studies are needed to determine the practicality and long-term clinical efficacy of these devices.

PDT Combination Therapy
Laser ablation may be combined with PDT to increase efficacy and prolong remission rates. In fact, laser ablation may be thought of as a physical drug-delivery system to boost uptake of topical agents—in this case, aminolevulinic acid and methyl aminolevulinate (MAL)—given that it disrupts the skin barrier.

In a comparative study of ablative fractional laser (AFXL)–assisted PDT and AFXL alone in 10 organ transplant recipients on immunosuppression with at least 5 AKs on each dorsal hand, participants were randomized to AFXL-PDT on one treatment side and PDT on the other side.⁶ Participants received AFXL in an initial lesion-directed pass and then a second field-directed pass of a fractional CO₂ laser. After AFXL exposure, methyl aminolevulinate was applied to the AFXL-PDT treatment side, with 3-hour occlusion. A total of 680 AKs were treated (335 in the AFXL-PDT group, 345 in the PDT group); results were stratified by the clinical grade of the lesion (1, slightly palpable; 2, moderately thick; 3, very thick or obvious). At 4-month follow-up, the AFXL-PDT group had a significantly higher median complete response rate of 73% compared to 31% in the AFXL group (P=.002). Interestingly, AFXL-PDT was also significantly more efficacious compared to AFXL for grades 1 (80% vs 37%; P=.02) and 2 (53% vs 7%, P=.009) AKs but not grade 3 AKs (4% vs 0%, P=.17).⁶

The combination of fractional CO₂ laser and PDT also demonstrated superiority to PDT.⁷ In a split-face investigation, 15 participants with bilateral symmetric areas of 2 to 10 AKs on the face or scalp were randomized to receive fractional CO₂ laser and MAL-PDT combination therapy on 1 treatment side and conventional MAL-PDT on the other side.⁷ The AFXL-PDT treatment side received laser ablation with immediate subsequent application of MAL to both treatment sides under 3-hour occlusion. At baseline, 103 AKs were treated by AFXL-PDT and 109 AKs were treated with conventional PDT. At 3-month follow-up, the AFXL-PDT treatment group exhibited a significantly higher rate of complete response (90%) compared to the conventional PDT group (67%)(P=.0002).⁷

Like the CO₂ laser, the Er:YAG laser has demonstrated superior results when used in combination with PDT to treat field cancerization compared to either treatment alone. In a comparison study, 93 patients with 2 to 10 AK lesions on the face or scalp were randomized to treatment with AFXL (Er:YAG laser) and MAL-PDT with 3-hour occlusion, AFXL (Er:YAG laser) and MAL-PDT with 2-hour occlusion, and MAL-PDT with 3-hour occlusion.⁸ A total of 440 baseline AK lesions on the face or scalp were treated. At 3-month follow-up, the AFXL-PDT (3-hour occlusion) group had the highest rate of complete response (91.7%), compared to 76.8% (P=.001) in the AFXL-PDT (2-hour occlusion) and 65.6% (P=.001) in the PDT groups, regardless of the grade of AK lesion. The AFXL-PDT (2-hour occlusion) treatment was also superior to PDT alone (P=.038). These findings were sustained at 12-month follow-up (84.8% in the AFXL-PDT [3-hour occlusion] group [P<.001, compared to others]; 67.5% in the AFXL-PDT [2-hour occlusion] group [P<.001, compared to 3-hour PDT]; 51.1% in the PDT group). Importantly, the AK lesion recurrence rate was also lowest in the AFL-PDT (3-hour occlusion) group (7.5% vs 12.1% and 22.1% in the AFXL-PDT [2-hour occlusion] and PDT groups, respectively; P=.007).⁸

Combination therapy with AFXL and daylight PDT (dPDT) may improve the tolerability of PDT and the efficacy rate of field therapy in organ transplant recipients. One study demonstrated the superiority of this combination therapy in a population of 16 organ transplant recipients on immunosuppressants with at least 2 moderate to severely thick AKs in each of 4 comparable areas in the same anatomic region.⁹ The 4 areas were randomized to a single session of AFXL-dPDT, dPDT alone, conventional PDT, or AFXL alone. Ablation was performed with a fractional Er:YAG laser. The AFXL-dPDT and dPDT alone groups received MAL for 2.5 hours without occlusion, and the conventional PDT group received MAL for 3 hours with occlusion. Daylight exposure in dPDT groups was initiated 30 minutes after MAL application for 2 hours total. A baseline total of 542 AKs were treated. At 3-month follow-up, the complete response rate was highest for the AFXL-dPDT group (74%) compared to dPDT alone (46%; P=.0262), conventional PDT (50%; P=.042), and AFXL alone (5%; P=.004). Pain scores for AFXL–dPDT and dPDT alone were significantly lower than for conventional PDT and AFXL alone (P<.001).⁹

Nonablative Lasers

By heating the dermis to induce neogenesis without destruction, nonablative lasers offer superior healing times compared to their ablative counterparts. Multiple treatments with nonablative lasers may be necessary for maximal effect. Four nonablative laser devices have demonstrated efficacy in the treatment of multiple AKs^10-14: (1) the Q-switched 1064-nm Nd:YAG laser, with or without a 532-nm potassium titanyl phosphate (KTP) laser; (2) the 1540-nm fractional erbium glass laser; (3) the 1550-nm fractional erbium-doped fiber laser; and (4) the 1927-nm fractional thulium laser (Table 3).

In a proof-of-concept study of the Q-switched Nd:YAG laser with the 532-nm KTP laser, 1 treatment session induced full remission of AKs in 10 patients at follow-up day 20, although the investigator did not grade improvement on a numerical scale.¹⁰ In a study of the fractional Q-switched 1064-nm Nd:YAG laser alone, 6 patients with trace or mild AKs received 4 treatment sessions at approximately 2-week intervals.¹⁴ All but 1 patient (who had trace AKs) had no AKs at 3-month follow-up.

The efficacy of the 1540-nm fractional erbium glass laser was examined in 17 participants with investigator-rated moderate-to-severe AK involvement of the scalp and face.¹² Participants were given 2 or 3 treatment sessions at 3- to 4-week intervals and were graded by blinded dermatologists on a quartile scale of 0 (no improvement), 1 (1%–25% improvement), 2 (26%–50% improvement), 3 (51%–75% improvement), or 4 (76%–100% improvement). At 3 months posttreatment, the average grade of improvement was 3.4.¹²

The 1550-nm fractional erbium-doped fiber laser was tested in 14 men with multiple facial AKs (range, 9–44 AKs [mean, 22.1 AKs]).¹¹ Participants received 5 treatment sessions at 2- to 4-week intervals, with majority energies used at 70 MJ and treatment level 11. The mean AK count was reduced significantly by 73.1%, 66.2%, and 55.6% at 1-, 3-, and 6-month follow-up, respectively (P<.001).¹¹

The 1927-nm fractional thulium laser showed promising results in 24 participants with facial AKs.¹³ Participants received up to 4 treatment sessions at intervals from 2 to 6 weeks at the investigators’ discretion. At baseline, patients had an average of 14.04 facial AKs. At 1-, 3-, and 6-month follow-up, participants exhibited 91.3%, 87.3%, and 86.6% reduction in AK counts, respectively. The mean AK count at 3-month follow-up was 1.88.¹³

Due to limited sample sizes and/or lack of quantifiable results and controls in these studies, more studies are needed to fully elucidate the role of nonablative lasers in the treatment of AK.

Future Directions

Iontophoresis involves the noninvasive induction of an electrical current to facilitate ion movement through the skin and may be a novel method to boost the efficacy of current field therapies. In the first known study of its kisnd, iontophoresis-assisted AFXL-PDT was found to be noninferior to conventional AFXL-PDT¹⁵; however, additional studies demonstrating its superiority are needed before more widespread clinical use is considered.

Pretreatment with AFXL prior to topical field-directed therapies also has been proposed.¹⁶ In a case series of 13 patients, combination therapy with AFXL and ingenol mebutate was shown to be superior to ingenol mebutate alone (AK clearance rate, 89.2% vs 72.1%, respectively; P<.001).¹⁶ Randomized studies with longer follow-up time are needed.

Conclusion

Ablative and nonablative laser systems have yielded limited data about their potential as monotherapies for treatment of multiple AKs and are unlikely to replace topical agents and PDT as a first-line modality in field-directed treatment at this time. More studies with a larger number of participants and long-term follow-up are needed for further clarification of efficacy, safety, and clinical feasibility. Nevertheless, fractional ablative lasers in combination with PDT have shown robust efficacy and a favorable safety profile for treatment of multiple AKs.^6-9 Further, this combination therapy exhibited a superior clearance rate and lower lesion recurrence in organ transplant recipients—a demographic that classically is difficult to treat.^6-9

With continued rapid evolution of laser systems and more widespread use in dermatology, monotherapy and combination therapy may offer a dynamic new option in field cancerization that can decrease disease burden and treatment frequency.

In cutaneous field cancerization, focal treatments such as cryotherapy are impractical, thus necessitating the use of field-directed therapies over the lesion and the surrounding skin field. Although evidence-based guidelines do not exist, field-directed therapy has been proposed in cases of 3 or more actinic keratoses (AKs) in a 25-cm² area or larger.¹ It can be further speculated that patients who are vulnerable to aggressive phenotypes of cutaneous malignancies, such as those with a genodermatosis or who are immunocompromised, necessitate a higher index of suspicion for field effect with even 1 or 2 AKs.

Current field-directed therapies include topical agents (imiquimod, fluorouracil, ingenol mebutate, and diclo-fenac), photodynamic therapy (PDT), and resurfacing procedures (lasers, chemical peels, dermabrasion). Although topical agents and PDT currently are gold standards in field treatment, the use of energy-based devices (ie, ablative and nonablative lasers) are attractive options as monotherapy or as part of a combination therapy. These devices are attractive options for field-directed therapy because they offer defined, customizable control of settings, allowing for optimal cosmesis and precision of therapy.

Principally, lasers function by damaging skin tissue to induce resurfacing, neocollagenesis, and vascular restructuring. Fractional versions of ablative and nonablative systems are available to target a fraction of the treatment area in evenly spaced microthermal zones and to minimize overall thermal damage.²

Given recent advances in laser systems and numerous investigations reported in the literature, a review of ablative and nonablative lasers that have been studied as treatment options for cutaneous field cancerization is provided, with a focus on treatment efficacy.

Ablative Lasers

Ablative lasers operate at higher wavelengths than nonablative lasers to destroy epidermal and dermal tissue. The 10,600-nm carbon dioxide (CO₂) and 2940-nm Er:YAG lasers have been heavily investigated for field therapy for multiple AKs, both as monotherapies (Table 1) and in combination with PDT (Table 2).

Monotherapy
One randomized trial with 5-year follow-up compared the efficacy of full-face pulsed CO₂ laser therapy, full-face trichloroacetic acid (TCA) peel 30%, and fluorouracil cream 5% (twice daily for 3 weeks) on AKs on the face and head.³ Thirty-one participants were randomized to the 3 treatment arms and a negative control arm. The mean AK counts at baseline for the CO₂, TCA, and fluorouracil treatment groups were 78.0, 83.7, and 61.8, respectively. At 3-month follow-up, all treatment groups had significant reductions in the mean AK count from baseline (CO₂ group, 92% [P=.03]; TCA group, 89% [P=.004]; fluorouracil group, 83% [P=.008]). No significant differences in efficacy among the treatment groups were noted. All 3 treatment groups had a demonstrably lower incidence of nonmelanoma skin cancer over 5-year follow-up compared to the control group (P<.001).³

In contrast to these promising results, the pulsed CO₂ laser showed only short-term efficacy in a split-face study of 12 participants with at least 5 facial or scalp AKs on each of 2 symmetric facial sides who were randomized to 1 treatment side.⁴ At 1-month follow-up, the treatment side exhibited significantly fewer AKs compared to the control side (47% vs 71% at baseline; P=.01), but the improvement was not sustained at 3-month follow-up (49% vs 57%; P=.47).⁴

In another study, the CO₂ laser was found to be inferior to 5-aminolevulinic acid PDT.⁵ Twenty-one participants who had at least 4 AKs in each symmetric half of a body region (head, hands, forearms) were randomized to PDT on 1 side and CO₂ laser therapy on the other. Median baseline AK counts for the PDT and CO₂ laser groups were 6 and 8, respectively. Both treatment groups exhibited significant median AK reduction from baseline 4 weeks posttreatment (PDT group, 82.1% [P<.05], CO₂ laser group, 100% [P<.05]); however. at 3 months posttreatment the PDT group had significantly higher absolute (P=.0155) and relative (P=.0362) reductions in AK count compared to the CO₂ laser group. One participant received a topical antibiotic for superficial infection on the PDT treatment side.⁵

Many questions remain regarding the practical application of laser ablation monotherapy for multiple AKs. More studies are needed to determine the practicality and long-term clinical efficacy of these devices.

PDT Combination Therapy
Laser ablation may be combined with PDT to increase efficacy and prolong remission rates. In fact, laser ablation may be thought of as a physical drug-delivery system to boost uptake of topical agents—in this case, aminolevulinic acid and methyl aminolevulinate (MAL)—given that it disrupts the skin barrier.

In a comparative study of ablative fractional laser (AFXL)–assisted PDT and AFXL alone in 10 organ transplant recipients on immunosuppression with at least 5 AKs on each dorsal hand, participants were randomized to AFXL-PDT on one treatment side and PDT on the other side.⁶ Participants received AFXL in an initial lesion-directed pass and then a second field-directed pass of a fractional CO₂ laser. After AFXL exposure, methyl aminolevulinate was applied to the AFXL-PDT treatment side, with 3-hour occlusion. A total of 680 AKs were treated (335 in the AFXL-PDT group, 345 in the PDT group); results were stratified by the clinical grade of the lesion (1, slightly palpable; 2, moderately thick; 3, very thick or obvious). At 4-month follow-up, the AFXL-PDT group had a significantly higher median complete response rate of 73% compared to 31% in the AFXL group (P=.002). Interestingly, AFXL-PDT was also significantly more efficacious compared to AFXL for grades 1 (80% vs 37%; P=.02) and 2 (53% vs 7%, P=.009) AKs but not grade 3 AKs (4% vs 0%, P=.17).⁶

The combination of fractional CO₂ laser and PDT also demonstrated superiority to PDT.⁷ In a split-face investigation, 15 participants with bilateral symmetric areas of 2 to 10 AKs on the face or scalp were randomized to receive fractional CO₂ laser and MAL-PDT combination therapy on 1 treatment side and conventional MAL-PDT on the other side.⁷ The AFXL-PDT treatment side received laser ablation with immediate subsequent application of MAL to both treatment sides under 3-hour occlusion. At baseline, 103 AKs were treated by AFXL-PDT and 109 AKs were treated with conventional PDT. At 3-month follow-up, the AFXL-PDT treatment group exhibited a significantly higher rate of complete response (90%) compared to the conventional PDT group (67%)(P=.0002).⁷

Like the CO₂ laser, the Er:YAG laser has demonstrated superior results when used in combination with PDT to treat field cancerization compared to either treatment alone. In a comparison study, 93 patients with 2 to 10 AK lesions on the face or scalp were randomized to treatment with AFXL (Er:YAG laser) and MAL-PDT with 3-hour occlusion, AFXL (Er:YAG laser) and MAL-PDT with 2-hour occlusion, and MAL-PDT with 3-hour occlusion.⁸ A total of 440 baseline AK lesions on the face or scalp were treated. At 3-month follow-up, the AFXL-PDT (3-hour occlusion) group had the highest rate of complete response (91.7%), compared to 76.8% (P=.001) in the AFXL-PDT (2-hour occlusion) and 65.6% (P=.001) in the PDT groups, regardless of the grade of AK lesion. The AFXL-PDT (2-hour occlusion) treatment was also superior to PDT alone (P=.038). These findings were sustained at 12-month follow-up (84.8% in the AFXL-PDT [3-hour occlusion] group [P<.001, compared to others]; 67.5% in the AFXL-PDT [2-hour occlusion] group [P<.001, compared to 3-hour PDT]; 51.1% in the PDT group). Importantly, the AK lesion recurrence rate was also lowest in the AFL-PDT (3-hour occlusion) group (7.5% vs 12.1% and 22.1% in the AFXL-PDT [2-hour occlusion] and PDT groups, respectively; P=.007).⁸

Combination therapy with AFXL and daylight PDT (dPDT) may improve the tolerability of PDT and the efficacy rate of field therapy in organ transplant recipients. One study demonstrated the superiority of this combination therapy in a population of 16 organ transplant recipients on immunosuppressants with at least 2 moderate to severely thick AKs in each of 4 comparable areas in the same anatomic region.⁹ The 4 areas were randomized to a single session of AFXL-dPDT, dPDT alone, conventional PDT, or AFXL alone. Ablation was performed with a fractional Er:YAG laser. The AFXL-dPDT and dPDT alone groups received MAL for 2.5 hours without occlusion, and the conventional PDT group received MAL for 3 hours with occlusion. Daylight exposure in dPDT groups was initiated 30 minutes after MAL application for 2 hours total. A baseline total of 542 AKs were treated. At 3-month follow-up, the complete response rate was highest for the AFXL-dPDT group (74%) compared to dPDT alone (46%; P=.0262), conventional PDT (50%; P=.042), and AFXL alone (5%; P=.004). Pain scores for AFXL–dPDT and dPDT alone were significantly lower than for conventional PDT and AFXL alone (P<.001).⁹

Nonablative Lasers

By heating the dermis to induce neogenesis without destruction, nonablative lasers offer superior healing times compared to their ablative counterparts. Multiple treatments with nonablative lasers may be necessary for maximal effect. Four nonablative laser devices have demonstrated efficacy in the treatment of multiple AKs^10-14: (1) the Q-switched 1064-nm Nd:YAG laser, with or without a 532-nm potassium titanyl phosphate (KTP) laser; (2) the 1540-nm fractional erbium glass laser; (3) the 1550-nm fractional erbium-doped fiber laser; and (4) the 1927-nm fractional thulium laser (Table 3).

In a proof-of-concept study of the Q-switched Nd:YAG laser with the 532-nm KTP laser, 1 treatment session induced full remission of AKs in 10 patients at follow-up day 20, although the investigator did not grade improvement on a numerical scale.¹⁰ In a study of the fractional Q-switched 1064-nm Nd:YAG laser alone, 6 patients with trace or mild AKs received 4 treatment sessions at approximately 2-week intervals.¹⁴ All but 1 patient (who had trace AKs) had no AKs at 3-month follow-up.

The efficacy of the 1540-nm fractional erbium glass laser was examined in 17 participants with investigator-rated moderate-to-severe AK involvement of the scalp and face.¹² Participants were given 2 or 3 treatment sessions at 3- to 4-week intervals and were graded by blinded dermatologists on a quartile scale of 0 (no improvement), 1 (1%–25% improvement), 2 (26%–50% improvement), 3 (51%–75% improvement), or 4 (76%–100% improvement). At 3 months posttreatment, the average grade of improvement was 3.4.¹²

The 1550-nm fractional erbium-doped fiber laser was tested in 14 men with multiple facial AKs (range, 9–44 AKs [mean, 22.1 AKs]).¹¹ Participants received 5 treatment sessions at 2- to 4-week intervals, with majority energies used at 70 MJ and treatment level 11. The mean AK count was reduced significantly by 73.1%, 66.2%, and 55.6% at 1-, 3-, and 6-month follow-up, respectively (P<.001).¹¹

The 1927-nm fractional thulium laser showed promising results in 24 participants with facial AKs.¹³ Participants received up to 4 treatment sessions at intervals from 2 to 6 weeks at the investigators’ discretion. At baseline, patients had an average of 14.04 facial AKs. At 1-, 3-, and 6-month follow-up, participants exhibited 91.3%, 87.3%, and 86.6% reduction in AK counts, respectively. The mean AK count at 3-month follow-up was 1.88.¹³

Due to limited sample sizes and/or lack of quantifiable results and controls in these studies, more studies are needed to fully elucidate the role of nonablative lasers in the treatment of AK.

Future Directions

Iontophoresis involves the noninvasive induction of an electrical current to facilitate ion movement through the skin and may be a novel method to boost the efficacy of current field therapies. In the first known study of its kisnd, iontophoresis-assisted AFXL-PDT was found to be noninferior to conventional AFXL-PDT¹⁵; however, additional studies demonstrating its superiority are needed before more widespread clinical use is considered.

Pretreatment with AFXL prior to topical field-directed therapies also has been proposed.¹⁶ In a case series of 13 patients, combination therapy with AFXL and ingenol mebutate was shown to be superior to ingenol mebutate alone (AK clearance rate, 89.2% vs 72.1%, respectively; P<.001).¹⁶ Randomized studies with longer follow-up time are needed.

Conclusion

Ablative and nonablative laser systems have yielded limited data about their potential as monotherapies for treatment of multiple AKs and are unlikely to replace topical agents and PDT as a first-line modality in field-directed treatment at this time. More studies with a larger number of participants and long-term follow-up are needed for further clarification of efficacy, safety, and clinical feasibility. Nevertheless, fractional ablative lasers in combination with PDT have shown robust efficacy and a favorable safety profile for treatment of multiple AKs.^6-9 Further, this combination therapy exhibited a superior clearance rate and lower lesion recurrence in organ transplant recipients—a demographic that classically is difficult to treat.^6-9

With continued rapid evolution of laser systems and more widespread use in dermatology, monotherapy and combination therapy may offer a dynamic new option in field cancerization that can decrease disease burden and treatment frequency.

DALLAS – One year after patients underwent treatment of basal cell carcinoma (BCC) with the 1064-nm Nd:YAG laser, no recurrences have occurred, according to early results from a study being conducted at two centers.

“The 1064-nm Nd:YAG laser is a promising noninvasive treatment approach for treating basal cell carcinoma,” Arisa E. Ortiz, MD, said at the annual conference of the American Society for Laser Medicine and Surgery. “Clearance rates are comparable to or better than other topical modalities such as electrodesiccation and curettage and topical imiquimod. It’s a reasonable alternative for treatment patients with multiple tumors or those who are poor surgical candidates.”

“Laser surgery also provides precision that ordinary surgical techniques cannot match. Despite the obvious obstacles, there is no reason such surgical techniques cannot be expanded someday to other internal cutaneous tumors, including GI tumors. To some extent this is happening already. Vascular lasers are being used to treat a bleeding disorder of the colon known as angiodysplasia. Cautious exploration of laser- and light-based treatments should be further explored as a means of sparing tissue and surgical morbidity.”

Dr. Ortiz disclosed that she has received grant funding from Sienna and Revance, as well as equipment from BTL, Invasix, and Sciton. She has received consulting fees from Alastin, Merz, and Sciton; honoraria from Alastin, Cutera, Invasix, and Sciton; and she holds ownership interest with Allergan. She also has served on the advisory boards for Alastin, Allergan, Invasix, Rodan + Fields, Sciton, Sienna, and Merz.

Dr. Avram disclosed that he serves on the medical advisory board of Sciton and on the scientific advisory boards of Sienna Biopharmaceuticals, Cytrellis, and Allergan. He is also a consultant for Merz Aesthetics, Allergan, Soliton, Invasix, and Revance and has intellectual property with Cytrellis. He also holds stock options with Cytrellis, Invasix, and Zalea.

dbrunk@mdedge.com

DALLAS – One year after patients underwent treatment of basal cell carcinoma (BCC) with the 1064-nm Nd:YAG laser, no recurrences have occurred, according to early results from a study being conducted at two centers.

“The 1064-nm Nd:YAG laser is a promising noninvasive treatment approach for treating basal cell carcinoma,” Arisa E. Ortiz, MD, said at the annual conference of the American Society for Laser Medicine and Surgery. “Clearance rates are comparable to or better than other topical modalities such as electrodesiccation and curettage and topical imiquimod. It’s a reasonable alternative for treatment patients with multiple tumors or those who are poor surgical candidates.”

“Laser surgery also provides precision that ordinary surgical techniques cannot match. Despite the obvious obstacles, there is no reason such surgical techniques cannot be expanded someday to other internal cutaneous tumors, including GI tumors. To some extent this is happening already. Vascular lasers are being used to treat a bleeding disorder of the colon known as angiodysplasia. Cautious exploration of laser- and light-based treatments should be further explored as a means of sparing tissue and surgical morbidity.”

Dr. Ortiz disclosed that she has received grant funding from Sienna and Revance, as well as equipment from BTL, Invasix, and Sciton. She has received consulting fees from Alastin, Merz, and Sciton; honoraria from Alastin, Cutera, Invasix, and Sciton; and she holds ownership interest with Allergan. She also has served on the advisory boards for Alastin, Allergan, Invasix, Rodan + Fields, Sciton, Sienna, and Merz.

Dr. Avram disclosed that he serves on the medical advisory board of Sciton and on the scientific advisory boards of Sienna Biopharmaceuticals, Cytrellis, and Allergan. He is also a consultant for Merz Aesthetics, Allergan, Soliton, Invasix, and Revance and has intellectual property with Cytrellis. He also holds stock options with Cytrellis, Invasix, and Zalea.

dbrunk@mdedge.com

DALLAS – One year after patients underwent treatment of basal cell carcinoma (BCC) with the 1064-nm Nd:YAG laser, no recurrences have occurred, according to early results from a study being conducted at two centers.

“The 1064-nm Nd:YAG laser is a promising noninvasive treatment approach for treating basal cell carcinoma,” Arisa E. Ortiz, MD, said at the annual conference of the American Society for Laser Medicine and Surgery. “Clearance rates are comparable to or better than other topical modalities such as electrodesiccation and curettage and topical imiquimod. It’s a reasonable alternative for treatment patients with multiple tumors or those who are poor surgical candidates.”

“Laser surgery also provides precision that ordinary surgical techniques cannot match. Despite the obvious obstacles, there is no reason such surgical techniques cannot be expanded someday to other internal cutaneous tumors, including GI tumors. To some extent this is happening already. Vascular lasers are being used to treat a bleeding disorder of the colon known as angiodysplasia. Cautious exploration of laser- and light-based treatments should be further explored as a means of sparing tissue and surgical morbidity.”

Dr. Ortiz disclosed that she has received grant funding from Sienna and Revance, as well as equipment from BTL, Invasix, and Sciton. She has received consulting fees from Alastin, Merz, and Sciton; honoraria from Alastin, Cutera, Invasix, and Sciton; and she holds ownership interest with Allergan. She also has served on the advisory boards for Alastin, Allergan, Invasix, Rodan + Fields, Sciton, Sienna, and Merz.

Dr. Avram disclosed that he serves on the medical advisory board of Sciton and on the scientific advisory boards of Sienna Biopharmaceuticals, Cytrellis, and Allergan. He is also a consultant for Merz Aesthetics, Allergan, Soliton, Invasix, and Revance and has intellectual property with Cytrellis. He also holds stock options with Cytrellis, Invasix, and Zalea.

dbrunk@mdedge.com

LAS VEGAS – For women with larger hepatic adenomas, current guidelines suggest reassessment at 6 months after oral contraceptive withdrawal to determine whether resection is warranted.

However, emerging data show reassessing at that time point may lead to overtreatment, according to Laura M. Kulik, MD, professor of medicine (gastroenterology and hepatology), radiology and surgery (organ transplantation), Northwestern University, Chicago.

“There’s been some controversy that 6 months may be too short,” Dr. Kulik said at the inaugural Perspectives in Digestive Diseases meeting held by Global Academy for Medical Education.

Unlike other benign liver lesions, hepatic adenomas can hemorrhage and transform to hepatocellular carcinoma. Current guidelines from the European Association for the Study of the Liver state that larger lesions (i.e., 5 cm or greater on baseline imaging) are associated with a higher risk of complications. According to one systematic review cited in the document, almost all cases of hemorrhage or spontaneous rupture occur in lesions 5 cm or larger.

Oral contraceptive use has been associated with a 30- to 40-fold increase in hepatic adenoma incidence, according to the guidelines.

All men with hepatic adenomas should undergo resection or curative treatment, the guidelines say, since they have a significantly higher risk of hepatocellular carcinoma.

By contrast, women with hepatic adenomas larger than 5 cm should discontinue oral contraceptives – which may lead to tumor regression in some cases – and should be reassessed 6 months later with contrast-enhanced MRI; if the lesion is still greater than 5 cm at that time, they should be considered for resection or curative treatment, the guidelines say.

However, authors of a retrospective cohort study have challenged that advice, suggesting that a 6-month follow-up may not always be long enough to see adequate tumor regression (HPB 2017 Apr;19[Suppl 1]:S3).

LAS VEGAS – For women with larger hepatic adenomas, current guidelines suggest reassessment at 6 months after oral contraceptive withdrawal to determine whether resection is warranted.

However, emerging data show reassessing at that time point may lead to overtreatment, according to Laura M. Kulik, MD, professor of medicine (gastroenterology and hepatology), radiology and surgery (organ transplantation), Northwestern University, Chicago.

“There’s been some controversy that 6 months may be too short,” Dr. Kulik said at the inaugural Perspectives in Digestive Diseases meeting held by Global Academy for Medical Education.

Unlike other benign liver lesions, hepatic adenomas can hemorrhage and transform to hepatocellular carcinoma. Current guidelines from the European Association for the Study of the Liver state that larger lesions (i.e., 5 cm or greater on baseline imaging) are associated with a higher risk of complications. According to one systematic review cited in the document, almost all cases of hemorrhage or spontaneous rupture occur in lesions 5 cm or larger.

Oral contraceptive use has been associated with a 30- to 40-fold increase in hepatic adenoma incidence, according to the guidelines.

All men with hepatic adenomas should undergo resection or curative treatment, the guidelines say, since they have a significantly higher risk of hepatocellular carcinoma.

By contrast, women with hepatic adenomas larger than 5 cm should discontinue oral contraceptives – which may lead to tumor regression in some cases – and should be reassessed 6 months later with contrast-enhanced MRI; if the lesion is still greater than 5 cm at that time, they should be considered for resection or curative treatment, the guidelines say.

However, authors of a retrospective cohort study have challenged that advice, suggesting that a 6-month follow-up may not always be long enough to see adequate tumor regression (HPB 2017 Apr;19[Suppl 1]:S3).

LAS VEGAS – For women with larger hepatic adenomas, current guidelines suggest reassessment at 6 months after oral contraceptive withdrawal to determine whether resection is warranted.

However, emerging data show reassessing at that time point may lead to overtreatment, according to Laura M. Kulik, MD, professor of medicine (gastroenterology and hepatology), radiology and surgery (organ transplantation), Northwestern University, Chicago.

“There’s been some controversy that 6 months may be too short,” Dr. Kulik said at the inaugural Perspectives in Digestive Diseases meeting held by Global Academy for Medical Education.

Unlike other benign liver lesions, hepatic adenomas can hemorrhage and transform to hepatocellular carcinoma. Current guidelines from the European Association for the Study of the Liver state that larger lesions (i.e., 5 cm or greater on baseline imaging) are associated with a higher risk of complications. According to one systematic review cited in the document, almost all cases of hemorrhage or spontaneous rupture occur in lesions 5 cm or larger.

Oral contraceptive use has been associated with a 30- to 40-fold increase in hepatic adenoma incidence, according to the guidelines.

All men with hepatic adenomas should undergo resection or curative treatment, the guidelines say, since they have a significantly higher risk of hepatocellular carcinoma.

By contrast, women with hepatic adenomas larger than 5 cm should discontinue oral contraceptives – which may lead to tumor regression in some cases – and should be reassessed 6 months later with contrast-enhanced MRI; if the lesion is still greater than 5 cm at that time, they should be considered for resection or curative treatment, the guidelines say.

However, authors of a retrospective cohort study have challenged that advice, suggesting that a 6-month follow-up may not always be long enough to see adequate tumor regression (HPB 2017 Apr;19[Suppl 1]:S3).

Early detection of melanoma, which is known to improve survival rates, remains a challenge for dermatologists. Suspicious pigmented lesions typically are evaluated via clinical examination and dermoscopy; however, new technologies are being developed to provide additional objective information for clinicians to incorporate into their biopsy decisions.

Multispectral digital skin lesion analysis (MSDSLA) uses 10 bands of visible and near-infrared light (430–950 nm) to image and analyze pigmented skin lesions (PSLs) down to 2.5 mm below the skin surface and measures the distribution of melanin using 75 unique algorithms to determine the degree of the morphologic disorder. Using a logical regression model previously validated on a set of 1632 PSLs, the probability of melanoma and probability of being a melanoma/PSL of high-risk malignant potential are then provided to the clinician.¹

In this study, we analyzed aggregate data from 7 prior studies^2-8 to better determine how MSDSLA impacts the biopsy decisions of dermatologists and nondermatologists following clinical examination and dermoscopic evaluation of PSLs.

Methods

A total of 855 practitioners (657 dermatologists, 126 dermatology residents, 72 nondermatologists [ie, primary care physicians, physician assistants, nurse practitioners]) in 7 prior reader studies (Table)^2-8 were shown a total of 62 clinical (distant and close-up) and dermoscopic images of PSLs (13 invasive melanomas, 10 melanomas in situ, 7 high-grade dysplastic nevi, 32 benign skin lesions including low-grade dysplastic nevi) previously analyzed by MSDSLA.^2-8 For each lesion evaluated, the practitioners were first asked if they would biopsy based on their review of the clinical and dermoscopic images and were asked again when given the associated MSDSLA information. Data were aggregated across all participants for the individual lesions presented in each reader study. Biopsy decisions were compared overall after evaluation of clinical and dermoscopic findings and then after evaluation of MSDSLA findings. Statistical analyses were performed using t-test and χ² analysis for proportions where appropriate.

Results

Overall sensitivity for the detection of melanoma or other high-grade PSLs improved from 70% on clinical and dermoscopic evaluation to 88% after MSDSLA information was provided (P<.0001), and specificity increased from 52% to 58% (P<.001). Diagnostic accuracy also improved from 59% on clinical evaluation to 69% after review of MSDSLA findings (P<.0001). The positive predictive value of biopsy decisions was 47% following clinical evaluation, which improved to 56% after evaluation of MSDSLA findings (P<.001), and the negative predictive value increased from 74% to 89% (P<.0001). The overall percentage of lesions selected for biopsy did not significantly change following MSDSLA data integration (57% vs 60%)(Figure). Given that similar numbers of lesions were biopsied with improved sensitivity and specificity, the integration of MSDSLA data into the biopsy decision led to an improved biopsy ratio (ratio of melanomas biopsied to total biopsies) and fewer unnecessary biopsies.

Comment

Our broad analysis further supported the findings of prior studies that decisions to biopsy clinically suspicious PSLs are more sensitive, specific, and accurate when practitioners are provided MSDSLA information following clinical examination.^2-8With no significant increase in the number of biopsies performed, the fact that all 5 of the standard diagnostic evaluation metrics (sensitivity, specificity, diagnostic accuracy, positive predictive value, negative predictive value) were improved after MSDSLA information was provided additionally supported this conclusion.

Given the evolution in health care economics, it is clear that greater emphasis will continue to be placed on superior, evidence-based, effective care. The reported diagnostic sensitivities and specificities of clinical evaluation and dermoscopy for melanoma detection vary widely throughout the literature, with sensitivities ranging from 58% to over 90% and specificities ranging from 77% to 99%.^9-11Diagnostic performance generally has been found to be higher among dermatologists than nondermatologists and is highest in specialized pigmented lesion clinics.¹²

Our study had several limitations. For this analysis to be more representative of lesion biopsy selection in the clinical setting, biopsy sensitivity (correctly identifying lesions appropriate for biopsy) vs melanoma sensitivity (identifying a lesion as melanoma) was used.¹³ The overall sensitivity found was within the range of prior studies,^2-8 but this approach may have potentially led to a lower specificity due to an increased number of lesions biopsied. Additionally, the melanomas selected for these studies were early (malignant melanoma in situ or mean thickness of invasive malignant melanoma of 0.3 mm), and the nonmelanomas (including low-grade dysplastic nevi) were not necessarily diagnostically straightforward. This may have led to the clinical and dermoscopic sensitivity and specificity noted being lower than in some prior studies.^9-11

The risk of missing a melanoma with MSDSLA devices has led manufacturers to strive for a high sensitivity for their devices, leading to lower specificity as a consequence. For this reason and other ambiguous practical considerations (eg, device and patient costs, difficulty with insurance reimbursement), the adoption of this technology into routine clinical practice has remained relatively static; however, using enhanced diagnostic technologies such as MSDSLA may help with more accurate identification of high-risk PSLs, thereby leading to earlier detection and overall less expensive, more cost-effective treatment of melanoma.

Early detection of melanoma, which is known to improve survival rates, remains a challenge for dermatologists. Suspicious pigmented lesions typically are evaluated via clinical examination and dermoscopy; however, new technologies are being developed to provide additional objective information for clinicians to incorporate into their biopsy decisions.

Multispectral digital skin lesion analysis (MSDSLA) uses 10 bands of visible and near-infrared light (430–950 nm) to image and analyze pigmented skin lesions (PSLs) down to 2.5 mm below the skin surface and measures the distribution of melanin using 75 unique algorithms to determine the degree of the morphologic disorder. Using a logical regression model previously validated on a set of 1632 PSLs, the probability of melanoma and probability of being a melanoma/PSL of high-risk malignant potential are then provided to the clinician.¹

In this study, we analyzed aggregate data from 7 prior studies^2-8 to better determine how MSDSLA impacts the biopsy decisions of dermatologists and nondermatologists following clinical examination and dermoscopic evaluation of PSLs.

Methods

A total of 855 practitioners (657 dermatologists, 126 dermatology residents, 72 nondermatologists [ie, primary care physicians, physician assistants, nurse practitioners]) in 7 prior reader studies (Table)^2-8 were shown a total of 62 clinical (distant and close-up) and dermoscopic images of PSLs (13 invasive melanomas, 10 melanomas in situ, 7 high-grade dysplastic nevi, 32 benign skin lesions including low-grade dysplastic nevi) previously analyzed by MSDSLA.^2-8 For each lesion evaluated, the practitioners were first asked if they would biopsy based on their review of the clinical and dermoscopic images and were asked again when given the associated MSDSLA information. Data were aggregated across all participants for the individual lesions presented in each reader study. Biopsy decisions were compared overall after evaluation of clinical and dermoscopic findings and then after evaluation of MSDSLA findings. Statistical analyses were performed using t-test and χ² analysis for proportions where appropriate.

Results

Overall sensitivity for the detection of melanoma or other high-grade PSLs improved from 70% on clinical and dermoscopic evaluation to 88% after MSDSLA information was provided (P<.0001), and specificity increased from 52% to 58% (P<.001). Diagnostic accuracy also improved from 59% on clinical evaluation to 69% after review of MSDSLA findings (P<.0001). The positive predictive value of biopsy decisions was 47% following clinical evaluation, which improved to 56% after evaluation of MSDSLA findings (P<.001), and the negative predictive value increased from 74% to 89% (P<.0001). The overall percentage of lesions selected for biopsy did not significantly change following MSDSLA data integration (57% vs 60%)(Figure). Given that similar numbers of lesions were biopsied with improved sensitivity and specificity, the integration of MSDSLA data into the biopsy decision led to an improved biopsy ratio (ratio of melanomas biopsied to total biopsies) and fewer unnecessary biopsies.

Comment

Our broad analysis further supported the findings of prior studies that decisions to biopsy clinically suspicious PSLs are more sensitive, specific, and accurate when practitioners are provided MSDSLA information following clinical examination.^2-8With no significant increase in the number of biopsies performed, the fact that all 5 of the standard diagnostic evaluation metrics (sensitivity, specificity, diagnostic accuracy, positive predictive value, negative predictive value) were improved after MSDSLA information was provided additionally supported this conclusion.

Given the evolution in health care economics, it is clear that greater emphasis will continue to be placed on superior, evidence-based, effective care. The reported diagnostic sensitivities and specificities of clinical evaluation and dermoscopy for melanoma detection vary widely throughout the literature, with sensitivities ranging from 58% to over 90% and specificities ranging from 77% to 99%.^9-11Diagnostic performance generally has been found to be higher among dermatologists than nondermatologists and is highest in specialized pigmented lesion clinics.¹²

Our study had several limitations. For this analysis to be more representative of lesion biopsy selection in the clinical setting, biopsy sensitivity (correctly identifying lesions appropriate for biopsy) vs melanoma sensitivity (identifying a lesion as melanoma) was used.¹³ The overall sensitivity found was within the range of prior studies,^2-8 but this approach may have potentially led to a lower specificity due to an increased number of lesions biopsied. Additionally, the melanomas selected for these studies were early (malignant melanoma in situ or mean thickness of invasive malignant melanoma of 0.3 mm), and the nonmelanomas (including low-grade dysplastic nevi) were not necessarily diagnostically straightforward. This may have led to the clinical and dermoscopic sensitivity and specificity noted being lower than in some prior studies.^9-11

The risk of missing a melanoma with MSDSLA devices has led manufacturers to strive for a high sensitivity for their devices, leading to lower specificity as a consequence. For this reason and other ambiguous practical considerations (eg, device and patient costs, difficulty with insurance reimbursement), the adoption of this technology into routine clinical practice has remained relatively static; however, using enhanced diagnostic technologies such as MSDSLA may help with more accurate identification of high-risk PSLs, thereby leading to earlier detection and overall less expensive, more cost-effective treatment of melanoma.

Early detection of melanoma, which is known to improve survival rates, remains a challenge for dermatologists. Suspicious pigmented lesions typically are evaluated via clinical examination and dermoscopy; however, new technologies are being developed to provide additional objective information for clinicians to incorporate into their biopsy decisions.

Multispectral digital skin lesion analysis (MSDSLA) uses 10 bands of visible and near-infrared light (430–950 nm) to image and analyze pigmented skin lesions (PSLs) down to 2.5 mm below the skin surface and measures the distribution of melanin using 75 unique algorithms to determine the degree of the morphologic disorder. Using a logical regression model previously validated on a set of 1632 PSLs, the probability of melanoma and probability of being a melanoma/PSL of high-risk malignant potential are then provided to the clinician.¹

In this study, we analyzed aggregate data from 7 prior studies^2-8 to better determine how MSDSLA impacts the biopsy decisions of dermatologists and nondermatologists following clinical examination and dermoscopic evaluation of PSLs.

Methods

A total of 855 practitioners (657 dermatologists, 126 dermatology residents, 72 nondermatologists [ie, primary care physicians, physician assistants, nurse practitioners]) in 7 prior reader studies (Table)^2-8 were shown a total of 62 clinical (distant and close-up) and dermoscopic images of PSLs (13 invasive melanomas, 10 melanomas in situ, 7 high-grade dysplastic nevi, 32 benign skin lesions including low-grade dysplastic nevi) previously analyzed by MSDSLA.^2-8 For each lesion evaluated, the practitioners were first asked if they would biopsy based on their review of the clinical and dermoscopic images and were asked again when given the associated MSDSLA information. Data were aggregated across all participants for the individual lesions presented in each reader study. Biopsy decisions were compared overall after evaluation of clinical and dermoscopic findings and then after evaluation of MSDSLA findings. Statistical analyses were performed using t-test and χ² analysis for proportions where appropriate.

Results

Overall sensitivity for the detection of melanoma or other high-grade PSLs improved from 70% on clinical and dermoscopic evaluation to 88% after MSDSLA information was provided (P<.0001), and specificity increased from 52% to 58% (P<.001). Diagnostic accuracy also improved from 59% on clinical evaluation to 69% after review of MSDSLA findings (P<.0001). The positive predictive value of biopsy decisions was 47% following clinical evaluation, which improved to 56% after evaluation of MSDSLA findings (P<.001), and the negative predictive value increased from 74% to 89% (P<.0001). The overall percentage of lesions selected for biopsy did not significantly change following MSDSLA data integration (57% vs 60%)(Figure). Given that similar numbers of lesions were biopsied with improved sensitivity and specificity, the integration of MSDSLA data into the biopsy decision led to an improved biopsy ratio (ratio of melanomas biopsied to total biopsies) and fewer unnecessary biopsies.

Comment

Our broad analysis further supported the findings of prior studies that decisions to biopsy clinically suspicious PSLs are more sensitive, specific, and accurate when practitioners are provided MSDSLA information following clinical examination.^2-8With no significant increase in the number of biopsies performed, the fact that all 5 of the standard diagnostic evaluation metrics (sensitivity, specificity, diagnostic accuracy, positive predictive value, negative predictive value) were improved after MSDSLA information was provided additionally supported this conclusion.

Given the evolution in health care economics, it is clear that greater emphasis will continue to be placed on superior, evidence-based, effective care. The reported diagnostic sensitivities and specificities of clinical evaluation and dermoscopy for melanoma detection vary widely throughout the literature, with sensitivities ranging from 58% to over 90% and specificities ranging from 77% to 99%.^9-11Diagnostic performance generally has been found to be higher among dermatologists than nondermatologists and is highest in specialized pigmented lesion clinics.¹²

Our study had several limitations. For this analysis to be more representative of lesion biopsy selection in the clinical setting, biopsy sensitivity (correctly identifying lesions appropriate for biopsy) vs melanoma sensitivity (identifying a lesion as melanoma) was used.¹³ The overall sensitivity found was within the range of prior studies,^2-8 but this approach may have potentially led to a lower specificity due to an increased number of lesions biopsied. Additionally, the melanomas selected for these studies were early (malignant melanoma in situ or mean thickness of invasive malignant melanoma of 0.3 mm), and the nonmelanomas (including low-grade dysplastic nevi) were not necessarily diagnostically straightforward. This may have led to the clinical and dermoscopic sensitivity and specificity noted being lower than in some prior studies.^9-11

The risk of missing a melanoma with MSDSLA devices has led manufacturers to strive for a high sensitivity for their devices, leading to lower specificity as a consequence. For this reason and other ambiguous practical considerations (eg, device and patient costs, difficulty with insurance reimbursement), the adoption of this technology into routine clinical practice has remained relatively static; however, using enhanced diagnostic technologies such as MSDSLA may help with more accurate identification of high-risk PSLs, thereby leading to earlier detection and overall less expensive, more cost-effective treatment of melanoma.

Telemedicine arose from the need to provide critical and timely advice directly to health care providers and patients in remote or resource-scarce settings. Whether by radio, telephone, or other means of telecommunication technology, the US military has long utilized telemedicine. What started as a way to expedite the delivery of emergency consultations and medical expertise to remote populations in need has since evolved into a billion-dollar innovation industry that is poised to improve health care efficiency and access to specialist care as well as to lower health care costs for all patients.

Teledermatology in the Military

A primary mission of military medicine is to keep service members anywhere in the world in good health on the job during training, combat, and humanitarian operations.¹ Telemedicine greatly supports this mission by bringing the expertise of medical specialists to service members in the field without the cost or risks of travel for physicians. Telemedicine also is effective in promoting timely triage of patients and administration of the most appropriate levels of care. With the advent and globalization of high-speed wireless networks, advancements in telemedicine continue to develop and are becoming increasingly useful in military medicine.

As a specialty, dermatology is heavily reliant on visual information and therefore is particularly amenable to telemedicine applications. The rising popularity of such services has led to the development of the term teledermatology. While early teledermatology services were provided using radio, telephone, fax, and videoconferencing,² three distinct visual methods typically are used today, including (1) store-and-forward (S&F), (2) live-interactive, and (3) a hybrid of the two.³ Military dermatology predominantly utilizes an S&F system, as still photographs of lesions generally are preferred over video for more focused visualization.

In 2004, the US Army Medical Department established a centralized telemedicine program using Army Knowledge Online,¹ an S&F system that allows providers in remote locations to store and forward information about a patient’s clinical history along with digital photographs of the patient’s condition to a military dermatologist to review and make a diagnosis or suggest a treatment from a different location at a later time. Using this platform to provide asynchronous teledermatology services avoids the logistics required to schedule appointments and promotes convenience and more efficient use of physicians’ time and resources.

Given the ease of use of S&F systems among military practitioners, dermatology became one of the most heavily utilized teleconsultation specialties within the Army Knowledge Online system, accounting for 40% of the 10,817 consultations initiated from April 2004 to December 2012.⁵ It also is important to note that skin conditions historically account for 15% to 75% of outpatient visits during wartime; therefore, there is a need for dermatologic consultations, as primary care providers typically are responsible for providing dermatologic care to these patients.⁶ Because of the high demand for and low volume of US military dermatologists, the use of teledermatology (ie, Amy Knowledge Online) in the US military became a helpful educational tool and specialist extender for many primary care providers in the military.

Teledermatology in the military has evolved to not only provide timely and efficient care but also to reduce health care costs. In a retrospective evaluation of the US Department of Defense’s teledermatology consultation program from April 2004 to December 2012, as many as 98% of teledermatology consultations were answered within 24 hours of submission, 46 medical evacuations were avoided, and 41 medical evacuations were facilitated.⁴ In a study of teledermatology services used by deployed clinicians in Iraq from January 2005 to January 2009, it was estimated that teledermatology services would help save the military approximately $30.4 million among 2157 dermatology patients.⁷

Advances in Teledermatology

While the military continues to use S&F teleconsultations—a model in which a deployed referring clinician sends information to a military dermatologist for diagnosis and/or management recommendations—a number of teledermatology programs have been developed for civilians that provide additional advantages over standard face-to-face dermatology care. The advantages of S&F teledermatology applications are many, including faster communication with dermatology providers, diagnostic concordance comparable to face-to-face appointments, cost-effective care for patients, the ability to educate providers remotely,⁸ and similar outcomes to in-person care.⁹ However, as to be expected, in-person care remains the gold standard, especially when diagnostic accuracy depends on biopsy findings. A recent systematic review of teledermatology applications in the diagnosis and management of skin cancer showed that the diagnostic accuracy of in-person dermatology consultations remained higher than the accuracy provided by teledermatology consultations; however, as a result of additional technological advances in the quality of digital photography, some investigators have reported high accuracy when macroscopic and dermoscopic images were used in tandem.¹⁰

The development of the smartphone along with advances in digital photography and consumer-friendly mobile applications has allowed for the emergence of direct-to-consumer (DTC) teledermatology applications. Regardless of the user’s ability, the quality of photographs taken with smartphones has improved, as standard features such as high-resolution cameras with image stabilization, automatic focus, and lighting have become commonplace. The popularity of smartphone technology also has increased, with nearly 75% of all adults and more than 90% of adults younger than 35 years of age owning a smartphone according to a 2016 survey.¹¹

In 2015, there were at least 29 DTC teledermatology applications available on various mobile platforms,¹² accounting for an estimated 1.25 million teleconsultations with providers.¹³ Teledermatology platforms such as DermatologistOnCall and Spruce Health have made accessing dermatologic care convenient, timely, and affordable for patients via patient-friendly mobile applications. Direct-to-consumer telemedicine allows patients to communicate directly with a specialist without the need for a referral from a primary care provider–gatekeeper.¹⁴

Regular access to dermatologic care is especially important for patients who have chronic skin conditions. Several unique practice models have emerged as innovative solutions to providing more convenient and timely care. For example, Curology (https://curology.com) is an online teledermatology practice specializing in acne treatment. The cost to the patient includes unlimited dermatology consultations via a web application and custom-made prescription topical medication sent by mail. Clarify Medical (www.clarifymed.com) makes phototherapy easy for patients and health care providers. Although narrowband UVB treatment traditionally is administered in a dermatologist’s office 3 times weekly for several months until a skin condition has cleared, this smartphone application facilitates convenient, at-home phototherapy. An app-enabled light source allows patients to treat themselves in their own homes within the parameters of a physician’s prescription.

Although DTC teledermatology practices are convenient for many patients and providers, some have been criticized for providing poor quality of care¹² or facilitating fragmented care by not integrating with established electronic health record (EHR) systems.¹⁵ As a result, recommended practice guidelines for DTC teledermatology have been developed by the American Academy of Dermatology and some state medical boards.¹⁶ Moreover, several EHR systems, such as Epic (www.epic.com) and Modernizing Medicine’s EMA (www.modmed.com), have developed fully integrated S&F teledermatology platforms to be incorporated with established brick-and-mortar care.¹⁷

The Future of Teledermatology in the Military

The Army Knowledge Online telemedicine platform used by the US military has continued to be useful, particularly when treating patients in remote locations, and shows promise for improving routine domestic dermatology care. It has reduced the number of medical evacuations and improved care for those who do not have access to a dermatologist.⁴ Furthermore, one study noted that most consultations submitted via teledermatology applications from a combat zone received a diagnosis and treatment recommendation from a military dermatologist faster than they would have stateside, where the wait often is 4 to 8 weeks. On average, a teledermatology consultation from Afghanistan was answered in less than 6 hours.⁴ Although this response time might not be realistic for all dermatology practices, there clearly is potential in certain situations and utilizing certain models of care to diagnose and treat more patients more efficiently utilizing teledermatology applications than in an in-person office visit. A review of 658 teledermatology consultations in the US military from January 2011 to December 2012 revealed that the leading diagnoses were eczematous dermatitis (14%), contact dermatitis (9%), nonmelanoma skin cancer (5%), psoriasis (4%), and urticaria (4%).⁴ Increased use of teledermatology evaluation of these conditions in routine US-based military practice could help expedite care, decrease patient travel time, and utilize in-clinic dermatologist time more efficiently. Teledermatology visits for postoperative concerns also have demonstrated utility and convenience for triage and management of patients in the civilian setting and may be an additional novel use of teledermatology in the military setting.¹⁸ With the use of an integrated S&F teledermatology platform within an existing EHR system that is paired with a secure patient mobile application that allows easy upload of photos, medical history, and messaging, it can be argued that quality of life could greatly be enhanced for both military patients and providers.

Limitations of Teledermatology

Certainly, there are and will always be limitations to teledermatology. Even as digital photography improves, the quality and context of clinical images are user dependent, and key associated skin findings in other locations of the body can be missed. The ability to palpate the skin also is lacking in virtual encounters. Therefore, teledermatology might be considered most appropriate for specific diseases and conditions (eg, acne, psoriasis, eczema). Embracing teledermatology does not mean replacing in-person care; rather, it should be seen as an adjunct used to manage the high demand for dermatology expertise in military and civilian practice. For the US military, the promise and potential to embrace innovation in providing dermatologic care is there, as long as there are leaders to continue to champion it. In the current state of health care, many of the perceived barriers of teledermatology applications have already been overcome, including lack of training, lack of reimbursement, and perceived medicolegal risks.¹⁹

The US Federal Government is a large entity, and it will undoubtedly take time and effort to implement new and innovative programs such as the ones described here in the military. The first step in implementation is awareness that the possibilities exist; then, with the cooperation of dermatologists and support from the chain of command, it will be possible to incorporate advances in teledermatology and cultivate new ones.

Final Thoughts

The S&F teledermatology method used in the military setting has become commonplace in both military and civilian settings alike. Newer innovations in telemedicine, particularly in teledermatology, will continue to shape the future of military and civilian medicine for years to come.

Telemedicine arose from the need to provide critical and timely advice directly to health care providers and patients in remote or resource-scarce settings. Whether by radio, telephone, or other means of telecommunication technology, the US military has long utilized telemedicine. What started as a way to expedite the delivery of emergency consultations and medical expertise to remote populations in need has since evolved into a billion-dollar innovation industry that is poised to improve health care efficiency and access to specialist care as well as to lower health care costs for all patients.

Teledermatology in the Military

A primary mission of military medicine is to keep service members anywhere in the world in good health on the job during training, combat, and humanitarian operations.¹ Telemedicine greatly supports this mission by bringing the expertise of medical specialists to service members in the field without the cost or risks of travel for physicians. Telemedicine also is effective in promoting timely triage of patients and administration of the most appropriate levels of care. With the advent and globalization of high-speed wireless networks, advancements in telemedicine continue to develop and are becoming increasingly useful in military medicine.

As a specialty, dermatology is heavily reliant on visual information and therefore is particularly amenable to telemedicine applications. The rising popularity of such services has led to the development of the term teledermatology. While early teledermatology services were provided using radio, telephone, fax, and videoconferencing,² three distinct visual methods typically are used today, including (1) store-and-forward (S&F), (2) live-interactive, and (3) a hybrid of the two.³ Military dermatology predominantly utilizes an S&F system, as still photographs of lesions generally are preferred over video for more focused visualization.

In 2004, the US Army Medical Department established a centralized telemedicine program using Army Knowledge Online,¹ an S&F system that allows providers in remote locations to store and forward information about a patient’s clinical history along with digital photographs of the patient’s condition to a military dermatologist to review and make a diagnosis or suggest a treatment from a different location at a later time. Using this platform to provide asynchronous teledermatology services avoids the logistics required to schedule appointments and promotes convenience and more efficient use of physicians’ time and resources.

Given the ease of use of S&F systems among military practitioners, dermatology became one of the most heavily utilized teleconsultation specialties within the Army Knowledge Online system, accounting for 40% of the 10,817 consultations initiated from April 2004 to December 2012.⁵ It also is important to note that skin conditions historically account for 15% to 75% of outpatient visits during wartime; therefore, there is a need for dermatologic consultations, as primary care providers typically are responsible for providing dermatologic care to these patients.⁶ Because of the high demand for and low volume of US military dermatologists, the use of teledermatology (ie, Amy Knowledge Online) in the US military became a helpful educational tool and specialist extender for many primary care providers in the military.

Teledermatology in the military has evolved to not only provide timely and efficient care but also to reduce health care costs. In a retrospective evaluation of the US Department of Defense’s teledermatology consultation program from April 2004 to December 2012, as many as 98% of teledermatology consultations were answered within 24 hours of submission, 46 medical evacuations were avoided, and 41 medical evacuations were facilitated.⁴ In a study of teledermatology services used by deployed clinicians in Iraq from January 2005 to January 2009, it was estimated that teledermatology services would help save the military approximately $30.4 million among 2157 dermatology patients.⁷

Advances in Teledermatology

While the military continues to use S&F teleconsultations—a model in which a deployed referring clinician sends information to a military dermatologist for diagnosis and/or management recommendations—a number of teledermatology programs have been developed for civilians that provide additional advantages over standard face-to-face dermatology care. The advantages of S&F teledermatology applications are many, including faster communication with dermatology providers, diagnostic concordance comparable to face-to-face appointments, cost-effective care for patients, the ability to educate providers remotely,⁸ and similar outcomes to in-person care.⁹ However, as to be expected, in-person care remains the gold standard, especially when diagnostic accuracy depends on biopsy findings. A recent systematic review of teledermatology applications in the diagnosis and management of skin cancer showed that the diagnostic accuracy of in-person dermatology consultations remained higher than the accuracy provided by teledermatology consultations; however, as a result of additional technological advances in the quality of digital photography, some investigators have reported high accuracy when macroscopic and dermoscopic images were used in tandem.¹⁰

The development of the smartphone along with advances in digital photography and consumer-friendly mobile applications has allowed for the emergence of direct-to-consumer (DTC) teledermatology applications. Regardless of the user’s ability, the quality of photographs taken with smartphones has improved, as standard features such as high-resolution cameras with image stabilization, automatic focus, and lighting have become commonplace. The popularity of smartphone technology also has increased, with nearly 75% of all adults and more than 90% of adults younger than 35 years of age owning a smartphone according to a 2016 survey.¹¹

In 2015, there were at least 29 DTC teledermatology applications available on various mobile platforms,¹² accounting for an estimated 1.25 million teleconsultations with providers.¹³ Teledermatology platforms such as DermatologistOnCall and Spruce Health have made accessing dermatologic care convenient, timely, and affordable for patients via patient-friendly mobile applications. Direct-to-consumer telemedicine allows patients to communicate directly with a specialist without the need for a referral from a primary care provider–gatekeeper.¹⁴

Regular access to dermatologic care is especially important for patients who have chronic skin conditions. Several unique practice models have emerged as innovative solutions to providing more convenient and timely care. For example, Curology (https://curology.com) is an online teledermatology practice specializing in acne treatment. The cost to the patient includes unlimited dermatology consultations via a web application and custom-made prescription topical medication sent by mail. Clarify Medical (www.clarifymed.com) makes phototherapy easy for patients and health care providers. Although narrowband UVB treatment traditionally is administered in a dermatologist’s office 3 times weekly for several months until a skin condition has cleared, this smartphone application facilitates convenient, at-home phototherapy. An app-enabled light source allows patients to treat themselves in their own homes within the parameters of a physician’s prescription.

Although DTC teledermatology practices are convenient for many patients and providers, some have been criticized for providing poor quality of care¹² or facilitating fragmented care by not integrating with established electronic health record (EHR) systems.¹⁵ As a result, recommended practice guidelines for DTC teledermatology have been developed by the American Academy of Dermatology and some state medical boards.¹⁶ Moreover, several EHR systems, such as Epic (www.epic.com) and Modernizing Medicine’s EMA (www.modmed.com), have developed fully integrated S&F teledermatology platforms to be incorporated with established brick-and-mortar care.¹⁷

The Future of Teledermatology in the Military

The Army Knowledge Online telemedicine platform used by the US military has continued to be useful, particularly when treating patients in remote locations, and shows promise for improving routine domestic dermatology care. It has reduced the number of medical evacuations and improved care for those who do not have access to a dermatologist.⁴ Furthermore, one study noted that most consultations submitted via teledermatology applications from a combat zone received a diagnosis and treatment recommendation from a military dermatologist faster than they would have stateside, where the wait often is 4 to 8 weeks. On average, a teledermatology consultation from Afghanistan was answered in less than 6 hours.⁴ Although this response time might not be realistic for all dermatology practices, there clearly is potential in certain situations and utilizing certain models of care to diagnose and treat more patients more efficiently utilizing teledermatology applications than in an in-person office visit. A review of 658 teledermatology consultations in the US military from January 2011 to December 2012 revealed that the leading diagnoses were eczematous dermatitis (14%), contact dermatitis (9%), nonmelanoma skin cancer (5%), psoriasis (4%), and urticaria (4%).⁴ Increased use of teledermatology evaluation of these conditions in routine US-based military practice could help expedite care, decrease patient travel time, and utilize in-clinic dermatologist time more efficiently. Teledermatology visits for postoperative concerns also have demonstrated utility and convenience for triage and management of patients in the civilian setting and may be an additional novel use of teledermatology in the military setting.¹⁸ With the use of an integrated S&F teledermatology platform within an existing EHR system that is paired with a secure patient mobile application that allows easy upload of photos, medical history, and messaging, it can be argued that quality of life could greatly be enhanced for both military patients and providers.

Limitations of Teledermatology

Certainly, there are and will always be limitations to teledermatology. Even as digital photography improves, the quality and context of clinical images are user dependent, and key associated skin findings in other locations of the body can be missed. The ability to palpate the skin also is lacking in virtual encounters. Therefore, teledermatology might be considered most appropriate for specific diseases and conditions (eg, acne, psoriasis, eczema). Embracing teledermatology does not mean replacing in-person care; rather, it should be seen as an adjunct used to manage the high demand for dermatology expertise in military and civilian practice. For the US military, the promise and potential to embrace innovation in providing dermatologic care is there, as long as there are leaders to continue to champion it. In the current state of health care, many of the perceived barriers of teledermatology applications have already been overcome, including lack of training, lack of reimbursement, and perceived medicolegal risks.¹⁹

The US Federal Government is a large entity, and it will undoubtedly take time and effort to implement new and innovative programs such as the ones described here in the military. The first step in implementation is awareness that the possibilities exist; then, with the cooperation of dermatologists and support from the chain of command, it will be possible to incorporate advances in teledermatology and cultivate new ones.

Final Thoughts

The S&F teledermatology method used in the military setting has become commonplace in both military and civilian settings alike. Newer innovations in telemedicine, particularly in teledermatology, will continue to shape the future of military and civilian medicine for years to come.

Telemedicine arose from the need to provide critical and timely advice directly to health care providers and patients in remote or resource-scarce settings. Whether by radio, telephone, or other means of telecommunication technology, the US military has long utilized telemedicine. What started as a way to expedite the delivery of emergency consultations and medical expertise to remote populations in need has since evolved into a billion-dollar innovation industry that is poised to improve health care efficiency and access to specialist care as well as to lower health care costs for all patients.

Teledermatology in the Military

A primary mission of military medicine is to keep service members anywhere in the world in good health on the job during training, combat, and humanitarian operations.¹ Telemedicine greatly supports this mission by bringing the expertise of medical specialists to service members in the field without the cost or risks of travel for physicians. Telemedicine also is effective in promoting timely triage of patients and administration of the most appropriate levels of care. With the advent and globalization of high-speed wireless networks, advancements in telemedicine continue to develop and are becoming increasingly useful in military medicine.

As a specialty, dermatology is heavily reliant on visual information and therefore is particularly amenable to telemedicine applications. The rising popularity of such services has led to the development of the term teledermatology. While early teledermatology services were provided using radio, telephone, fax, and videoconferencing,² three distinct visual methods typically are used today, including (1) store-and-forward (S&F), (2) live-interactive, and (3) a hybrid of the two.³ Military dermatology predominantly utilizes an S&F system, as still photographs of lesions generally are preferred over video for more focused visualization.

In 2004, the US Army Medical Department established a centralized telemedicine program using Army Knowledge Online,¹ an S&F system that allows providers in remote locations to store and forward information about a patient’s clinical history along with digital photographs of the patient’s condition to a military dermatologist to review and make a diagnosis or suggest a treatment from a different location at a later time. Using this platform to provide asynchronous teledermatology services avoids the logistics required to schedule appointments and promotes convenience and more efficient use of physicians’ time and resources.

Given the ease of use of S&F systems among military practitioners, dermatology became one of the most heavily utilized teleconsultation specialties within the Army Knowledge Online system, accounting for 40% of the 10,817 consultations initiated from April 2004 to December 2012.⁵ It also is important to note that skin conditions historically account for 15% to 75% of outpatient visits during wartime; therefore, there is a need for dermatologic consultations, as primary care providers typically are responsible for providing dermatologic care to these patients.⁶ Because of the high demand for and low volume of US military dermatologists, the use of teledermatology (ie, Amy Knowledge Online) in the US military became a helpful educational tool and specialist extender for many primary care providers in the military.

Teledermatology in the military has evolved to not only provide timely and efficient care but also to reduce health care costs. In a retrospective evaluation of the US Department of Defense’s teledermatology consultation program from April 2004 to December 2012, as many as 98% of teledermatology consultations were answered within 24 hours of submission, 46 medical evacuations were avoided, and 41 medical evacuations were facilitated.⁴ In a study of teledermatology services used by deployed clinicians in Iraq from January 2005 to January 2009, it was estimated that teledermatology services would help save the military approximately $30.4 million among 2157 dermatology patients.⁷

Advances in Teledermatology

While the military continues to use S&F teleconsultations—a model in which a deployed referring clinician sends information to a military dermatologist for diagnosis and/or management recommendations—a number of teledermatology programs have been developed for civilians that provide additional advantages over standard face-to-face dermatology care. The advantages of S&F teledermatology applications are many, including faster communication with dermatology providers, diagnostic concordance comparable to face-to-face appointments, cost-effective care for patients, the ability to educate providers remotely,⁸ and similar outcomes to in-person care.⁹ However, as to be expected, in-person care remains the gold standard, especially when diagnostic accuracy depends on biopsy findings. A recent systematic review of teledermatology applications in the diagnosis and management of skin cancer showed that the diagnostic accuracy of in-person dermatology consultations remained higher than the accuracy provided by teledermatology consultations; however, as a result of additional technological advances in the quality of digital photography, some investigators have reported high accuracy when macroscopic and dermoscopic images were used in tandem.¹⁰

The development of the smartphone along with advances in digital photography and consumer-friendly mobile applications has allowed for the emergence of direct-to-consumer (DTC) teledermatology applications. Regardless of the user’s ability, the quality of photographs taken with smartphones has improved, as standard features such as high-resolution cameras with image stabilization, automatic focus, and lighting have become commonplace. The popularity of smartphone technology also has increased, with nearly 75% of all adults and more than 90% of adults younger than 35 years of age owning a smartphone according to a 2016 survey.¹¹

In 2015, there were at least 29 DTC teledermatology applications available on various mobile platforms,¹² accounting for an estimated 1.25 million teleconsultations with providers.¹³ Teledermatology platforms such as DermatologistOnCall and Spruce Health have made accessing dermatologic care convenient, timely, and affordable for patients via patient-friendly mobile applications. Direct-to-consumer telemedicine allows patients to communicate directly with a specialist without the need for a referral from a primary care provider–gatekeeper.¹⁴

Regular access to dermatologic care is especially important for patients who have chronic skin conditions. Several unique practice models have emerged as innovative solutions to providing more convenient and timely care. For example, Curology (https://curology.com) is an online teledermatology practice specializing in acne treatment. The cost to the patient includes unlimited dermatology consultations via a web application and custom-made prescription topical medication sent by mail. Clarify Medical (www.clarifymed.com) makes phototherapy easy for patients and health care providers. Although narrowband UVB treatment traditionally is administered in a dermatologist’s office 3 times weekly for several months until a skin condition has cleared, this smartphone application facilitates convenient, at-home phototherapy. An app-enabled light source allows patients to treat themselves in their own homes within the parameters of a physician’s prescription.

Although DTC teledermatology practices are convenient for many patients and providers, some have been criticized for providing poor quality of care¹² or facilitating fragmented care by not integrating with established electronic health record (EHR) systems.¹⁵ As a result, recommended practice guidelines for DTC teledermatology have been developed by the American Academy of Dermatology and some state medical boards.¹⁶ Moreover, several EHR systems, such as Epic (www.epic.com) and Modernizing Medicine’s EMA (www.modmed.com), have developed fully integrated S&F teledermatology platforms to be incorporated with established brick-and-mortar care.¹⁷

The Future of Teledermatology in the Military

The Army Knowledge Online telemedicine platform used by the US military has continued to be useful, particularly when treating patients in remote locations, and shows promise for improving routine domestic dermatology care. It has reduced the number of medical evacuations and improved care for those who do not have access to a dermatologist.⁴ Furthermore, one study noted that most consultations submitted via teledermatology applications from a combat zone received a diagnosis and treatment recommendation from a military dermatologist faster than they would have stateside, where the wait often is 4 to 8 weeks. On average, a teledermatology consultation from Afghanistan was answered in less than 6 hours.⁴ Although this response time might not be realistic for all dermatology practices, there clearly is potential in certain situations and utilizing certain models of care to diagnose and treat more patients more efficiently utilizing teledermatology applications than in an in-person office visit. A review of 658 teledermatology consultations in the US military from January 2011 to December 2012 revealed that the leading diagnoses were eczematous dermatitis (14%), contact dermatitis (9%), nonmelanoma skin cancer (5%), psoriasis (4%), and urticaria (4%).⁴ Increased use of teledermatology evaluation of these conditions in routine US-based military practice could help expedite care, decrease patient travel time, and utilize in-clinic dermatologist time more efficiently. Teledermatology visits for postoperative concerns also have demonstrated utility and convenience for triage and management of patients in the civilian setting and may be an additional novel use of teledermatology in the military setting.¹⁸ With the use of an integrated S&F teledermatology platform within an existing EHR system that is paired with a secure patient mobile application that allows easy upload of photos, medical history, and messaging, it can be argued that quality of life could greatly be enhanced for both military patients and providers.

Limitations of Teledermatology

Certainly, there are and will always be limitations to teledermatology. Even as digital photography improves, the quality and context of clinical images are user dependent, and key associated skin findings in other locations of the body can be missed. The ability to palpate the skin also is lacking in virtual encounters. Therefore, teledermatology might be considered most appropriate for specific diseases and conditions (eg, acne, psoriasis, eczema). Embracing teledermatology does not mean replacing in-person care; rather, it should be seen as an adjunct used to manage the high demand for dermatology expertise in military and civilian practice. For the US military, the promise and potential to embrace innovation in providing dermatologic care is there, as long as there are leaders to continue to champion it. In the current state of health care, many of the perceived barriers of teledermatology applications have already been overcome, including lack of training, lack of reimbursement, and perceived medicolegal risks.¹⁹

The US Federal Government is a large entity, and it will undoubtedly take time and effort to implement new and innovative programs such as the ones described here in the military. The first step in implementation is awareness that the possibilities exist; then, with the cooperation of dermatologists and support from the chain of command, it will be possible to incorporate advances in teledermatology and cultivate new ones.

Final Thoughts

The S&F teledermatology method used in the military setting has become commonplace in both military and civilian settings alike. Newer innovations in telemedicine, particularly in teledermatology, will continue to shape the future of military and civilian medicine for years to come.

CHICAGO – A combination of an immunostimulatory IL-15-based agent, ALT-803, with a therapeutic monoclonal antibody (mAb) against CD20, was well tolerated and had clinical activity in patients with indolent non-Hodgkin lymphoma (iNHL), according to preliminary findings from a phase 1 study.

“The cancer immunotherapy breakthrough that happened several years ago continues year after year, with a plethora of different modalities of immunotherapy at our disposal,” Todd A. Fehniger, MD, PhD, said at the annual meeting of the American Association for Cancer Research.

Immunotherapy with anti-CD20 mAbs, alone or in combination with chemotherapy, is a standard therapy for iNHL patients. Since iNHL cells express CD20, targeting it with mAbs triggers antitumor responses via cell surface receptors resulting in a potent antibody-dependent cellular toxicity. However, response in patients is highly heterogeneous, with relapse within a few months in a subset of patients. In addition, chemotherapeutic combinations can be toxic and result in serious and long-term complications.

“Relapsed or refractory iNHL is not curable and treatment strategies without long-term complications are needed,” said Dr. Fehniger, associate professor of medicine at Washington University, St. Louis.

In an attempt to address this, Dr. Fehniger and his colleagues combined rituximab, an anti-CD20 antibody, with a relatively new IL-15 agonist immunostimulatory agent called ALT-803.

In the phase 1 trial, the researchers enrolled patients with indolent non-Hodgkin lymphoma who had relapsed after at least 1 prior to CD20 antibody containing therapy. The study was a standard 3+3 dose escalation design with rituximab administered by intravenous infusion, 375 mg/m² in four weekly doses, followed by a rest and four consolidation doses every 8 weeks for four cycles.

ALT-803 was administered concurrently at dose levels of 1 mcg/kg, 3 mcg/kg, and 6 mcg/kg IV followed by 6 mcg/kg, 10 mcg/kg, 15 mcg/kg, and 20 mcg/kg subcutaneously.

SOURCE: Fehniger TA et al. AACR Annual Meeting, Abstract CT146.

CHICAGO – A combination of an immunostimulatory IL-15-based agent, ALT-803, with a therapeutic monoclonal antibody (mAb) against CD20, was well tolerated and had clinical activity in patients with indolent non-Hodgkin lymphoma (iNHL), according to preliminary findings from a phase 1 study.

“The cancer immunotherapy breakthrough that happened several years ago continues year after year, with a plethora of different modalities of immunotherapy at our disposal,” Todd A. Fehniger, MD, PhD, said at the annual meeting of the American Association for Cancer Research.

Immunotherapy with anti-CD20 mAbs, alone or in combination with chemotherapy, is a standard therapy for iNHL patients. Since iNHL cells express CD20, targeting it with mAbs triggers antitumor responses via cell surface receptors resulting in a potent antibody-dependent cellular toxicity. However, response in patients is highly heterogeneous, with relapse within a few months in a subset of patients. In addition, chemotherapeutic combinations can be toxic and result in serious and long-term complications.

“Relapsed or refractory iNHL is not curable and treatment strategies without long-term complications are needed,” said Dr. Fehniger, associate professor of medicine at Washington University, St. Louis.

In an attempt to address this, Dr. Fehniger and his colleagues combined rituximab, an anti-CD20 antibody, with a relatively new IL-15 agonist immunostimulatory agent called ALT-803.

In the phase 1 trial, the researchers enrolled patients with indolent non-Hodgkin lymphoma who had relapsed after at least 1 prior to CD20 antibody containing therapy. The study was a standard 3+3 dose escalation design with rituximab administered by intravenous infusion, 375 mg/m² in four weekly doses, followed by a rest and four consolidation doses every 8 weeks for four cycles.

ALT-803 was administered concurrently at dose levels of 1 mcg/kg, 3 mcg/kg, and 6 mcg/kg IV followed by 6 mcg/kg, 10 mcg/kg, 15 mcg/kg, and 20 mcg/kg subcutaneously.

SOURCE: Fehniger TA et al. AACR Annual Meeting, Abstract CT146.

CHICAGO – A combination of an immunostimulatory IL-15-based agent, ALT-803, with a therapeutic monoclonal antibody (mAb) against CD20, was well tolerated and had clinical activity in patients with indolent non-Hodgkin lymphoma (iNHL), according to preliminary findings from a phase 1 study.

“The cancer immunotherapy breakthrough that happened several years ago continues year after year, with a plethora of different modalities of immunotherapy at our disposal,” Todd A. Fehniger, MD, PhD, said at the annual meeting of the American Association for Cancer Research.

Immunotherapy with anti-CD20 mAbs, alone or in combination with chemotherapy, is a standard therapy for iNHL patients. Since iNHL cells express CD20, targeting it with mAbs triggers antitumor responses via cell surface receptors resulting in a potent antibody-dependent cellular toxicity. However, response in patients is highly heterogeneous, with relapse within a few months in a subset of patients. In addition, chemotherapeutic combinations can be toxic and result in serious and long-term complications.

“Relapsed or refractory iNHL is not curable and treatment strategies without long-term complications are needed,” said Dr. Fehniger, associate professor of medicine at Washington University, St. Louis.

In an attempt to address this, Dr. Fehniger and his colleagues combined rituximab, an anti-CD20 antibody, with a relatively new IL-15 agonist immunostimulatory agent called ALT-803.

In the phase 1 trial, the researchers enrolled patients with indolent non-Hodgkin lymphoma who had relapsed after at least 1 prior to CD20 antibody containing therapy. The study was a standard 3+3 dose escalation design with rituximab administered by intravenous infusion, 375 mg/m² in four weekly doses, followed by a rest and four consolidation doses every 8 weeks for four cycles.

ALT-803 was administered concurrently at dose levels of 1 mcg/kg, 3 mcg/kg, and 6 mcg/kg IV followed by 6 mcg/kg, 10 mcg/kg, 15 mcg/kg, and 20 mcg/kg subcutaneously.

SOURCE: Fehniger TA et al. AACR Annual Meeting, Abstract CT146.

Mohs micrographic surgery (MMS) is a specialized surgical technique for the treatment of melanoma and nonmelanoma skin cancers (NMSCs).^1-3 The procedure involves surgical excision, histopathologic examination, precise mapping of malignant tissue, and wound management. Indications for MMS in skin cancer patients include recurring lesions, lesions in high-risk anatomic locations, aggressive histologic subtypes (ie, morpheaform, micronodular, infiltrative, high-grade, poorly differentiated), perineural invasion, large lesion size (>2 cm in diameter), poorly defined lateral or vertical clinical borders, rapid growth of the lesion, immunocompromised status, and sites of positive margins on prior excision. The therapeutic advantages of MMS include tissue conservation and optimal margin control in cosmetically or functionally sensitive areas, such as acral sites (eg, hands, feet, digits).^1,3

The intricacies of the nail apparatus complicate diagnostic biopsy and precise delineation of peripheral margins in digital skin cancers; thus, early diagnosis and intraoperative histologic examination of the margins are essential. Traditionally, the surgical approach to subungual cutaneous tumors such as melanoma has included digital amputation⁴; however, a study of the treatment of subungual melanoma revealed no difference in survival based on the level of amputation, therefore advocating for less radical treatment.⁴

Interestingly, MMS for cutaneous tumors localized to the digits is not frequently reviewed in the dermatologic literature. We present a retrospective case series evaluating the clinical outcomes of digital melanoma and NMSCs treated with MMS.

Methods

A retrospective chart review was performed at a private dermatology practice to identify patients who underwent MMS for melanoma or NMSC localized to the digits from January 2009 to December 2014. All patients were treated in the office by 1 Mohs surgeon (A.H.) and were evaluated before and after MMS. Data were collected from the electronic medical record of the practice, including patient demographics, histopathologic diagnosis, tumor status (primary or recurrent lesion), anatomic site of the tumor, preoperative and postoperative size of the lesion, number of MMS stages, surgical repair technique, postoperative complications, and follow-up period.

Results

Twenty-seven patients (13 male, 14 female) with a total of 28 lesions (malignant melanoma or NMSC) localized to the digits were identified (Table). The mean age at the time of MMS was 64.07 years. Twelve (42.86%) patients were 70 years of age or older, 11 (39.29%) were between 50 and 69 years, and 5 (17.85%) were younger than 50 years. Fifteen (53.57%) of the lesions were localized to the fingers, and 13 (46.43%) were localized to the toes; 18 (64.3%) of the lesions were distal and 10 (35.7%) were proximal to the distal interphalangeal joint. The most common pathologic diagnosis was squamous cell carcinoma (SCC) in situ (12/28 [42.86%]), followed by melanoma in situ (6/28 [21.42%]), severely dysplastic nevus (4/28 [14.29%]), SCC (4/28 [14.29%]), acrospiroma (1/28 [3.57%]), and melanoma (1/28 [3.57%]).

Surgical techniques used for repair following MMS included xenograft (10/28 [35.71%]); split-thickness skin graft (7/28 [25.0%]); secondary intention (4/28 [14.29%]); flap (4/28 [14.29%]); full-thickness skin graft (2/28 [7.14%]); and complex closure (1/28 [3.57%]). Clinical preoperative, operative, and postoperative photos from Patient 21 in this series are shown here (Figure). Two patients required bony phalanx resection due to invasion of the tumor into the periosteum: 1 had a malignant melanoma (Breslow depth, 2.52 mm); the other had an SCC. In addition, following removal of a severely dysplastic nevus, debulked tissue revealed melanoma in 1 patient.

Postoperative complications were noted in 4 (14.29%) of 28 MMS procedures, including bacterial wound infection (3.57%), excess granulation tissue that required wound debridement (7.14%), and delay in wound healing (3.57%). Follow-up data were available for 25 of the 28 MMS procedures (mean follow-up, 35.4 months), during which no recurrences were observed.

Comment

Mohs micrographic surgery is a specialized technique used in the treatment of cutaneous tumors, including basal cell carcinoma, SCC, melanoma in situ, atypical fibroxanthoma, dermatofibrosarcoma protuberans, sebaceous carcinoma, microcystic adnexal carcinoma, and Merkel cell carcinoma, among other cutaneous tumors.^1-3 Mohs micrographic surgery provides the advantage of tissue conservation as well as optimal margin control in cosmetically or functionally sensitive areas while providing a higher cure rate than surgical excision. During the procedure, the surgical margin is examined histologically, thus ensuring definitive removal of the tumor but minimal loss of surrounding normal tissue.^1-3 Mohs micrographic surgery is particularly useful for treating lesions on acral sites (eg, hands, feet, and digits).^3-5

The treatment of digital skin cancers has evolved over the past 50 years with advancements resulting in more precise, tissue-sparing methods, in contrast to previous treatments such as amputation and wide local excision.⁶ More specifically, traditional digital amputation for the treatment of subungual melanoma has been reevaluated in multiple studies, which did not demonstrate a statistically significant difference in survival based on the level of amputation, thereby favoring less radical treatment.^4,6 Moehrle et al⁷ found no statistical difference in recurrence rate when comparing patients with digital melanomas treated with partial amputation and those treated with digit-sparing surgery with limited excision and histologic evaluation of margins. Additionally, in a study conducted by Lazar et al,⁸ no recurrence of 13 subungual malignancies treated with MMS that utilized a full-thickness graft was reported at 4-year follow-up. In a large retrospective series of digital melanomas treated with MMS, Terushkin et al⁵ reported that 96.5% (55/57) of patients with primary melanomas that were treated with MMS avoided amputation, and the 5- and 10-year melanoma-specific survival rates for all patients treated with MMS were 95.0% and 82.6%, respectively. Based on a review of PubMed articles indexed for MEDLINE using the search terms surgical treatment of digital melanoma and nonmelanoma skin cancers, Mohs micrographic surgery for melanoma and nonmelanoma skin cancer, and surgical treatment of subungual skin cancer, conservative functional surgical approaches have been found to be cosmetically favorable, whereas local recurrence and survival rates have been shown to be unaffected by the level and degree of amputation.^4,5

In our study, cutaneous malignancies were located most often on the fingers, and the most common skin cancer identified was SCC in situ. The literature has shown that SCC in situ and SCC are the most common cutaneous neoplasms of the digits and nail unit.⁹ The most common specific anatomic site of cutaneous malignancy in our study was the great toe, followed by the fourth finger. A study conducted by Tan et al⁹ revealed that the great toe was the most common location of melanoma of the nail bed and subungual region, followed by the thumb. In contrast, primary subungual SCCs occur most frequently on the finger, with rare cases involving the toes.¹⁰

The etiology of digital SCC may involve extensive sun exposure, chronic trauma and wounds, and viral infection.^9,11 More specifically, the dermatologic literature provides evidence of human papillomavirus (HPV) type 16 involvement in the pathogenesis of digital and periungual SCC. A genital-digital mechanism of spread has been implicated.^11,12 An increased recurrence rate of HPV-associated digital SCCs has been reported following MMS, likely secondary to residual postsurgical HPV infection.^11,12

Maintaining function and cosmesis of the hands, feet, and digits following MMS can be challenging, sometimes requiring skin grafts and flaps to close the defect. In the 28 MMS procedures evaluated in our study, 19 (67.9%) surgical defects were repaired with a graft (ie, split-thickness skin graft, full-thickness skin graft, xenograft), 4 (14.3%) with a flap (advancement and rotation), 4 (14.3%) by secondary intention, and 1 (3.6%) with primary complex closure.

Surgical grafts can be categorized based on the origin of the graft.^2,13 Autografts, derived from the patient’s skin, are the most frequently used dermatologic graft and can be further categorized as full-thickness skin grafts, which include the epidermis and the entire dermis, thus preserving adnexal structures, and split-thickness skin grafts, which include the epidermis and partial dermis.^2,13Xenografts (eg, porcine grafts) can be used to repair defects involving the mucosa and those with a large wound depth, exposed cartilage, and/or bony defects, as well as wounds with indeterminate tumor margins and in patients with medical comorbidities that might prevent or delay plans for immediate wound reconstruction (eg, diabetes, cardiovascular disease, autoimmune connective tissue disease).^13,14

A cross-sectional survey of fellowship-trained Mohs surgeons revealed that more than two-thirds of repairs for cutaneous acral cancers were performed using a primary closure technique, and one-fourth of closures were performed using secondary intention.¹⁵ Of the less frequently utilized skin-graft repairs, more were for acral lesions on the legs than on the arms.¹⁴ The type of procedure and graft used is dependent on multiple variables, including the anatomic location of the lesion and final size of the defect following MMS.² Similarly, the use of specific types of sutures depends on the anatomic location of the lesion, relative thickness of the skin, degree of tension, and desired cosmetic result.¹⁵ The expertise of a hand surgeon may be required, particularly in cases in which the extensor tendon of the distal interphalangeal joint is compromised, manifested by a droopy fingertip when the hand is held horizontally. Additionally, special attention should be paid to removing the entire nail matrix before skin grafting for subungual tumors to avoid nail growth under the skin graft.

Evaluation of debulked tissue from digital skin cancers proved to be important in our study. In Patient 21, debulked tissue revealed melanoma following removal of a severely dysplastic nevus. This finding emphasizes the importance of complete excision of such lesions, as remaining underlying portions of the lesion can reveal residual tumor of the same or different histopathology.

In a prospective study, MMS was shown to have a low rate (0.91%; 95% confidence interval, 0.38%-1.45%) of surgical site infection in the absence of prophylactic antibiotics.¹⁶ The highest rates of surgical site infection were closely associated with flap closure. In our study, most patients had an uncomplicated and successful postoperative recovery. Only 1 (3.57%) of the 28 MMS procedures (Patient 22) was complicated by a bacterial wound infection postoperatively. The lesion removed in this case was a severely dysplastic melanocytic nevus on the toe. Infection resolved after a course of oral antibiotics, but the underlying cause of the wound infection in the patient was unclear. Other postoperative complications in our study included delayed wound healing and excess granulation tissue requiring wound debridement.

There are limited data in the dermatologic literature regarding outcomes following MMS for the treatment of cutaneous malignancies localized to the digits. In our study, patients treated with MMS were evaluated for recurrence of the primary lesion during postoperative follow-up appointments at the office or with the patient’s referring dermatologist. Follow-up data evaluating tumor recurrence were obtained for 25 of the patients, demonstrating no recurrence (mean follow-up, 35.4 months). Longer follow-up data would be more informative, but our findings nonetheless demonstrate that MMS is an effective treatment option for cutaneous malignancies of the digits.

Additional limitations of this case review include its single-center and retrospective design, the small sample size, and 1 Mohs surgeon having performed all surgeries.

Conclusion

This study provides further evidence of the benefit of MMS for the treatment of malignant melanoma and NMSCs of the digits. This procedure provides margin-controlled excision of these malignant neoplasms while preserving maximal normal tissue, thereby providing patients with improved postoperative function and cosmesis. Long-term follow-up data demonstrating a lack of tumor recurrence underscores the assertion that MMS is safe and effective for the treatment of skin cancer of the digits.

Mohs micrographic surgery (MMS) is a specialized surgical technique for the treatment of melanoma and nonmelanoma skin cancers (NMSCs).^1-3 The procedure involves surgical excision, histopathologic examination, precise mapping of malignant tissue, and wound management. Indications for MMS in skin cancer patients include recurring lesions, lesions in high-risk anatomic locations, aggressive histologic subtypes (ie, morpheaform, micronodular, infiltrative, high-grade, poorly differentiated), perineural invasion, large lesion size (>2 cm in diameter), poorly defined lateral or vertical clinical borders, rapid growth of the lesion, immunocompromised status, and sites of positive margins on prior excision. The therapeutic advantages of MMS include tissue conservation and optimal margin control in cosmetically or functionally sensitive areas, such as acral sites (eg, hands, feet, digits).^1,3

The intricacies of the nail apparatus complicate diagnostic biopsy and precise delineation of peripheral margins in digital skin cancers; thus, early diagnosis and intraoperative histologic examination of the margins are essential. Traditionally, the surgical approach to subungual cutaneous tumors such as melanoma has included digital amputation⁴; however, a study of the treatment of subungual melanoma revealed no difference in survival based on the level of amputation, therefore advocating for less radical treatment.⁴

Interestingly, MMS for cutaneous tumors localized to the digits is not frequently reviewed in the dermatologic literature. We present a retrospective case series evaluating the clinical outcomes of digital melanoma and NMSCs treated with MMS.

Methods

A retrospective chart review was performed at a private dermatology practice to identify patients who underwent MMS for melanoma or NMSC localized to the digits from January 2009 to December 2014. All patients were treated in the office by 1 Mohs surgeon (A.H.) and were evaluated before and after MMS. Data were collected from the electronic medical record of the practice, including patient demographics, histopathologic diagnosis, tumor status (primary or recurrent lesion), anatomic site of the tumor, preoperative and postoperative size of the lesion, number of MMS stages, surgical repair technique, postoperative complications, and follow-up period.

Results

Twenty-seven patients (13 male, 14 female) with a total of 28 lesions (malignant melanoma or NMSC) localized to the digits were identified (Table). The mean age at the time of MMS was 64.07 years. Twelve (42.86%) patients were 70 years of age or older, 11 (39.29%) were between 50 and 69 years, and 5 (17.85%) were younger than 50 years. Fifteen (53.57%) of the lesions were localized to the fingers, and 13 (46.43%) were localized to the toes; 18 (64.3%) of the lesions were distal and 10 (35.7%) were proximal to the distal interphalangeal joint. The most common pathologic diagnosis was squamous cell carcinoma (SCC) in situ (12/28 [42.86%]), followed by melanoma in situ (6/28 [21.42%]), severely dysplastic nevus (4/28 [14.29%]), SCC (4/28 [14.29%]), acrospiroma (1/28 [3.57%]), and melanoma (1/28 [3.57%]).

Surgical techniques used for repair following MMS included xenograft (10/28 [35.71%]); split-thickness skin graft (7/28 [25.0%]); secondary intention (4/28 [14.29%]); flap (4/28 [14.29%]); full-thickness skin graft (2/28 [7.14%]); and complex closure (1/28 [3.57%]). Clinical preoperative, operative, and postoperative photos from Patient 21 in this series are shown here (Figure). Two patients required bony phalanx resection due to invasion of the tumor into the periosteum: 1 had a malignant melanoma (Breslow depth, 2.52 mm); the other had an SCC. In addition, following removal of a severely dysplastic nevus, debulked tissue revealed melanoma in 1 patient.

Postoperative complications were noted in 4 (14.29%) of 28 MMS procedures, including bacterial wound infection (3.57%), excess granulation tissue that required wound debridement (7.14%), and delay in wound healing (3.57%). Follow-up data were available for 25 of the 28 MMS procedures (mean follow-up, 35.4 months), during which no recurrences were observed.

Comment

Mohs micrographic surgery is a specialized technique used in the treatment of cutaneous tumors, including basal cell carcinoma, SCC, melanoma in situ, atypical fibroxanthoma, dermatofibrosarcoma protuberans, sebaceous carcinoma, microcystic adnexal carcinoma, and Merkel cell carcinoma, among other cutaneous tumors.^1-3 Mohs micrographic surgery provides the advantage of tissue conservation as well as optimal margin control in cosmetically or functionally sensitive areas while providing a higher cure rate than surgical excision. During the procedure, the surgical margin is examined histologically, thus ensuring definitive removal of the tumor but minimal loss of surrounding normal tissue.^1-3 Mohs micrographic surgery is particularly useful for treating lesions on acral sites (eg, hands, feet, and digits).^3-5

The treatment of digital skin cancers has evolved over the past 50 years with advancements resulting in more precise, tissue-sparing methods, in contrast to previous treatments such as amputation and wide local excision.⁶ More specifically, traditional digital amputation for the treatment of subungual melanoma has been reevaluated in multiple studies, which did not demonstrate a statistically significant difference in survival based on the level of amputation, thereby favoring less radical treatment.^4,6 Moehrle et al⁷ found no statistical difference in recurrence rate when comparing patients with digital melanomas treated with partial amputation and those treated with digit-sparing surgery with limited excision and histologic evaluation of margins. Additionally, in a study conducted by Lazar et al,⁸ no recurrence of 13 subungual malignancies treated with MMS that utilized a full-thickness graft was reported at 4-year follow-up. In a large retrospective series of digital melanomas treated with MMS, Terushkin et al⁵ reported that 96.5% (55/57) of patients with primary melanomas that were treated with MMS avoided amputation, and the 5- and 10-year melanoma-specific survival rates for all patients treated with MMS were 95.0% and 82.6%, respectively. Based on a review of PubMed articles indexed for MEDLINE using the search terms surgical treatment of digital melanoma and nonmelanoma skin cancers, Mohs micrographic surgery for melanoma and nonmelanoma skin cancer, and surgical treatment of subungual skin cancer, conservative functional surgical approaches have been found to be cosmetically favorable, whereas local recurrence and survival rates have been shown to be unaffected by the level and degree of amputation.^4,5

In our study, cutaneous malignancies were located most often on the fingers, and the most common skin cancer identified was SCC in situ. The literature has shown that SCC in situ and SCC are the most common cutaneous neoplasms of the digits and nail unit.⁹ The most common specific anatomic site of cutaneous malignancy in our study was the great toe, followed by the fourth finger. A study conducted by Tan et al⁹ revealed that the great toe was the most common location of melanoma of the nail bed and subungual region, followed by the thumb. In contrast, primary subungual SCCs occur most frequently on the finger, with rare cases involving the toes.¹⁰

The etiology of digital SCC may involve extensive sun exposure, chronic trauma and wounds, and viral infection.^9,11 More specifically, the dermatologic literature provides evidence of human papillomavirus (HPV) type 16 involvement in the pathogenesis of digital and periungual SCC. A genital-digital mechanism of spread has been implicated.^11,12 An increased recurrence rate of HPV-associated digital SCCs has been reported following MMS, likely secondary to residual postsurgical HPV infection.^11,12

Maintaining function and cosmesis of the hands, feet, and digits following MMS can be challenging, sometimes requiring skin grafts and flaps to close the defect. In the 28 MMS procedures evaluated in our study, 19 (67.9%) surgical defects were repaired with a graft (ie, split-thickness skin graft, full-thickness skin graft, xenograft), 4 (14.3%) with a flap (advancement and rotation), 4 (14.3%) by secondary intention, and 1 (3.6%) with primary complex closure.

Surgical grafts can be categorized based on the origin of the graft.^2,13 Autografts, derived from the patient’s skin, are the most frequently used dermatologic graft and can be further categorized as full-thickness skin grafts, which include the epidermis and the entire dermis, thus preserving adnexal structures, and split-thickness skin grafts, which include the epidermis and partial dermis.^2,13Xenografts (eg, porcine grafts) can be used to repair defects involving the mucosa and those with a large wound depth, exposed cartilage, and/or bony defects, as well as wounds with indeterminate tumor margins and in patients with medical comorbidities that might prevent or delay plans for immediate wound reconstruction (eg, diabetes, cardiovascular disease, autoimmune connective tissue disease).^13,14

A cross-sectional survey of fellowship-trained Mohs surgeons revealed that more than two-thirds of repairs for cutaneous acral cancers were performed using a primary closure technique, and one-fourth of closures were performed using secondary intention.¹⁵ Of the less frequently utilized skin-graft repairs, more were for acral lesions on the legs than on the arms.¹⁴ The type of procedure and graft used is dependent on multiple variables, including the anatomic location of the lesion and final size of the defect following MMS.² Similarly, the use of specific types of sutures depends on the anatomic location of the lesion, relative thickness of the skin, degree of tension, and desired cosmetic result.¹⁵ The expertise of a hand surgeon may be required, particularly in cases in which the extensor tendon of the distal interphalangeal joint is compromised, manifested by a droopy fingertip when the hand is held horizontally. Additionally, special attention should be paid to removing the entire nail matrix before skin grafting for subungual tumors to avoid nail growth under the skin graft.

Evaluation of debulked tissue from digital skin cancers proved to be important in our study. In Patient 21, debulked tissue revealed melanoma following removal of a severely dysplastic nevus. This finding emphasizes the importance of complete excision of such lesions, as remaining underlying portions of the lesion can reveal residual tumor of the same or different histopathology.

In a prospective study, MMS was shown to have a low rate (0.91%; 95% confidence interval, 0.38%-1.45%) of surgical site infection in the absence of prophylactic antibiotics.¹⁶ The highest rates of surgical site infection were closely associated with flap closure. In our study, most patients had an uncomplicated and successful postoperative recovery. Only 1 (3.57%) of the 28 MMS procedures (Patient 22) was complicated by a bacterial wound infection postoperatively. The lesion removed in this case was a severely dysplastic melanocytic nevus on the toe. Infection resolved after a course of oral antibiotics, but the underlying cause of the wound infection in the patient was unclear. Other postoperative complications in our study included delayed wound healing and excess granulation tissue requiring wound debridement.

There are limited data in the dermatologic literature regarding outcomes following MMS for the treatment of cutaneous malignancies localized to the digits. In our study, patients treated with MMS were evaluated for recurrence of the primary lesion during postoperative follow-up appointments at the office or with the patient’s referring dermatologist. Follow-up data evaluating tumor recurrence were obtained for 25 of the patients, demonstrating no recurrence (mean follow-up, 35.4 months). Longer follow-up data would be more informative, but our findings nonetheless demonstrate that MMS is an effective treatment option for cutaneous malignancies of the digits.

Additional limitations of this case review include its single-center and retrospective design, the small sample size, and 1 Mohs surgeon having performed all surgeries.

Conclusion

This study provides further evidence of the benefit of MMS for the treatment of malignant melanoma and NMSCs of the digits. This procedure provides margin-controlled excision of these malignant neoplasms while preserving maximal normal tissue, thereby providing patients with improved postoperative function and cosmesis. Long-term follow-up data demonstrating a lack of tumor recurrence underscores the assertion that MMS is safe and effective for the treatment of skin cancer of the digits.

Mohs micrographic surgery (MMS) is a specialized surgical technique for the treatment of melanoma and nonmelanoma skin cancers (NMSCs).^1-3 The procedure involves surgical excision, histopathologic examination, precise mapping of malignant tissue, and wound management. Indications for MMS in skin cancer patients include recurring lesions, lesions in high-risk anatomic locations, aggressive histologic subtypes (ie, morpheaform, micronodular, infiltrative, high-grade, poorly differentiated), perineural invasion, large lesion size (>2 cm in diameter), poorly defined lateral or vertical clinical borders, rapid growth of the lesion, immunocompromised status, and sites of positive margins on prior excision. The therapeutic advantages of MMS include tissue conservation and optimal margin control in cosmetically or functionally sensitive areas, such as acral sites (eg, hands, feet, digits).^1,3

The intricacies of the nail apparatus complicate diagnostic biopsy and precise delineation of peripheral margins in digital skin cancers; thus, early diagnosis and intraoperative histologic examination of the margins are essential. Traditionally, the surgical approach to subungual cutaneous tumors such as melanoma has included digital amputation⁴; however, a study of the treatment of subungual melanoma revealed no difference in survival based on the level of amputation, therefore advocating for less radical treatment.⁴

Interestingly, MMS for cutaneous tumors localized to the digits is not frequently reviewed in the dermatologic literature. We present a retrospective case series evaluating the clinical outcomes of digital melanoma and NMSCs treated with MMS.

Methods

A retrospective chart review was performed at a private dermatology practice to identify patients who underwent MMS for melanoma or NMSC localized to the digits from January 2009 to December 2014. All patients were treated in the office by 1 Mohs surgeon (A.H.) and were evaluated before and after MMS. Data were collected from the electronic medical record of the practice, including patient demographics, histopathologic diagnosis, tumor status (primary or recurrent lesion), anatomic site of the tumor, preoperative and postoperative size of the lesion, number of MMS stages, surgical repair technique, postoperative complications, and follow-up period.

Results

Twenty-seven patients (13 male, 14 female) with a total of 28 lesions (malignant melanoma or NMSC) localized to the digits were identified (Table). The mean age at the time of MMS was 64.07 years. Twelve (42.86%) patients were 70 years of age or older, 11 (39.29%) were between 50 and 69 years, and 5 (17.85%) were younger than 50 years. Fifteen (53.57%) of the lesions were localized to the fingers, and 13 (46.43%) were localized to the toes; 18 (64.3%) of the lesions were distal and 10 (35.7%) were proximal to the distal interphalangeal joint. The most common pathologic diagnosis was squamous cell carcinoma (SCC) in situ (12/28 [42.86%]), followed by melanoma in situ (6/28 [21.42%]), severely dysplastic nevus (4/28 [14.29%]), SCC (4/28 [14.29%]), acrospiroma (1/28 [3.57%]), and melanoma (1/28 [3.57%]).

Surgical techniques used for repair following MMS included xenograft (10/28 [35.71%]); split-thickness skin graft (7/28 [25.0%]); secondary intention (4/28 [14.29%]); flap (4/28 [14.29%]); full-thickness skin graft (2/28 [7.14%]); and complex closure (1/28 [3.57%]). Clinical preoperative, operative, and postoperative photos from Patient 21 in this series are shown here (Figure). Two patients required bony phalanx resection due to invasion of the tumor into the periosteum: 1 had a malignant melanoma (Breslow depth, 2.52 mm); the other had an SCC. In addition, following removal of a severely dysplastic nevus, debulked tissue revealed melanoma in 1 patient.

Postoperative complications were noted in 4 (14.29%) of 28 MMS procedures, including bacterial wound infection (3.57%), excess granulation tissue that required wound debridement (7.14%), and delay in wound healing (3.57%). Follow-up data were available for 25 of the 28 MMS procedures (mean follow-up, 35.4 months), during which no recurrences were observed.

Comment

Mohs micrographic surgery is a specialized technique used in the treatment of cutaneous tumors, including basal cell carcinoma, SCC, melanoma in situ, atypical fibroxanthoma, dermatofibrosarcoma protuberans, sebaceous carcinoma, microcystic adnexal carcinoma, and Merkel cell carcinoma, among other cutaneous tumors.^1-3 Mohs micrographic surgery provides the advantage of tissue conservation as well as optimal margin control in cosmetically or functionally sensitive areas while providing a higher cure rate than surgical excision. During the procedure, the surgical margin is examined histologically, thus ensuring definitive removal of the tumor but minimal loss of surrounding normal tissue.^1-3 Mohs micrographic surgery is particularly useful for treating lesions on acral sites (eg, hands, feet, and digits).^3-5

The treatment of digital skin cancers has evolved over the past 50 years with advancements resulting in more precise, tissue-sparing methods, in contrast to previous treatments such as amputation and wide local excision.⁶ More specifically, traditional digital amputation for the treatment of subungual melanoma has been reevaluated in multiple studies, which did not demonstrate a statistically significant difference in survival based on the level of amputation, thereby favoring less radical treatment.^4,6 Moehrle et al⁷ found no statistical difference in recurrence rate when comparing patients with digital melanomas treated with partial amputation and those treated with digit-sparing surgery with limited excision and histologic evaluation of margins. Additionally, in a study conducted by Lazar et al,⁸ no recurrence of 13 subungual malignancies treated with MMS that utilized a full-thickness graft was reported at 4-year follow-up. In a large retrospective series of digital melanomas treated with MMS, Terushkin et al⁵ reported that 96.5% (55/57) of patients with primary melanomas that were treated with MMS avoided amputation, and the 5- and 10-year melanoma-specific survival rates for all patients treated with MMS were 95.0% and 82.6%, respectively. Based on a review of PubMed articles indexed for MEDLINE using the search terms surgical treatment of digital melanoma and nonmelanoma skin cancers, Mohs micrographic surgery for melanoma and nonmelanoma skin cancer, and surgical treatment of subungual skin cancer, conservative functional surgical approaches have been found to be cosmetically favorable, whereas local recurrence and survival rates have been shown to be unaffected by the level and degree of amputation.^4,5

In our study, cutaneous malignancies were located most often on the fingers, and the most common skin cancer identified was SCC in situ. The literature has shown that SCC in situ and SCC are the most common cutaneous neoplasms of the digits and nail unit.⁹ The most common specific anatomic site of cutaneous malignancy in our study was the great toe, followed by the fourth finger. A study conducted by Tan et al⁹ revealed that the great toe was the most common location of melanoma of the nail bed and subungual region, followed by the thumb. In contrast, primary subungual SCCs occur most frequently on the finger, with rare cases involving the toes.¹⁰

The etiology of digital SCC may involve extensive sun exposure, chronic trauma and wounds, and viral infection.^9,11 More specifically, the dermatologic literature provides evidence of human papillomavirus (HPV) type 16 involvement in the pathogenesis of digital and periungual SCC. A genital-digital mechanism of spread has been implicated.^11,12 An increased recurrence rate of HPV-associated digital SCCs has been reported following MMS, likely secondary to residual postsurgical HPV infection.^11,12

Maintaining function and cosmesis of the hands, feet, and digits following MMS can be challenging, sometimes requiring skin grafts and flaps to close the defect. In the 28 MMS procedures evaluated in our study, 19 (67.9%) surgical defects were repaired with a graft (ie, split-thickness skin graft, full-thickness skin graft, xenograft), 4 (14.3%) with a flap (advancement and rotation), 4 (14.3%) by secondary intention, and 1 (3.6%) with primary complex closure.

Surgical grafts can be categorized based on the origin of the graft.^2,13 Autografts, derived from the patient’s skin, are the most frequently used dermatologic graft and can be further categorized as full-thickness skin grafts, which include the epidermis and the entire dermis, thus preserving adnexal structures, and split-thickness skin grafts, which include the epidermis and partial dermis.^2,13Xenografts (eg, porcine grafts) can be used to repair defects involving the mucosa and those with a large wound depth, exposed cartilage, and/or bony defects, as well as wounds with indeterminate tumor margins and in patients with medical comorbidities that might prevent or delay plans for immediate wound reconstruction (eg, diabetes, cardiovascular disease, autoimmune connective tissue disease).^13,14

A cross-sectional survey of fellowship-trained Mohs surgeons revealed that more than two-thirds of repairs for cutaneous acral cancers were performed using a primary closure technique, and one-fourth of closures were performed using secondary intention.¹⁵ Of the less frequently utilized skin-graft repairs, more were for acral lesions on the legs than on the arms.¹⁴ The type of procedure and graft used is dependent on multiple variables, including the anatomic location of the lesion and final size of the defect following MMS.² Similarly, the use of specific types of sutures depends on the anatomic location of the lesion, relative thickness of the skin, degree of tension, and desired cosmetic result.¹⁵ The expertise of a hand surgeon may be required, particularly in cases in which the extensor tendon of the distal interphalangeal joint is compromised, manifested by a droopy fingertip when the hand is held horizontally. Additionally, special attention should be paid to removing the entire nail matrix before skin grafting for subungual tumors to avoid nail growth under the skin graft.

Evaluation of debulked tissue from digital skin cancers proved to be important in our study. In Patient 21, debulked tissue revealed melanoma following removal of a severely dysplastic nevus. This finding emphasizes the importance of complete excision of such lesions, as remaining underlying portions of the lesion can reveal residual tumor of the same or different histopathology.

In a prospective study, MMS was shown to have a low rate (0.91%; 95% confidence interval, 0.38%-1.45%) of surgical site infection in the absence of prophylactic antibiotics.¹⁶ The highest rates of surgical site infection were closely associated with flap closure. In our study, most patients had an uncomplicated and successful postoperative recovery. Only 1 (3.57%) of the 28 MMS procedures (Patient 22) was complicated by a bacterial wound infection postoperatively. The lesion removed in this case was a severely dysplastic melanocytic nevus on the toe. Infection resolved after a course of oral antibiotics, but the underlying cause of the wound infection in the patient was unclear. Other postoperative complications in our study included delayed wound healing and excess granulation tissue requiring wound debridement.

There are limited data in the dermatologic literature regarding outcomes following MMS for the treatment of cutaneous malignancies localized to the digits. In our study, patients treated with MMS were evaluated for recurrence of the primary lesion during postoperative follow-up appointments at the office or with the patient’s referring dermatologist. Follow-up data evaluating tumor recurrence were obtained for 25 of the patients, demonstrating no recurrence (mean follow-up, 35.4 months). Longer follow-up data would be more informative, but our findings nonetheless demonstrate that MMS is an effective treatment option for cutaneous malignancies of the digits.

Additional limitations of this case review include its single-center and retrospective design, the small sample size, and 1 Mohs surgeon having performed all surgeries.

Conclusion

This study provides further evidence of the benefit of MMS for the treatment of malignant melanoma and NMSCs of the digits. This procedure provides margin-controlled excision of these malignant neoplasms while preserving maximal normal tissue, thereby providing patients with improved postoperative function and cosmesis. Long-term follow-up data demonstrating a lack of tumor recurrence underscores the assertion that MMS is safe and effective for the treatment of skin cancer of the digits.

In critically ill patients, treating blood glucose with a low target of 80-110 mg/dL was associated with a lower risk of 30-day mortality compared with patients with a target of 90-140 mg/dL, according to results of a retrospective cohort analysis.

With the computerized intravenous insulin protocol used in the study, the strict target could be achieved with a low rate of hypoglycemia, the authors wrote. The analysis was published in the journal CHEST^®.

monkeybusinessimages/Thinkstock

Unadjusted 30-day mortality was significantly lower in the 80-110–mg/dL group compared with the 90-140–mg/dL group (4.3% vs. 9.2%, respectively; P less than .001), according to the investigators.

Furthermore, logistic regression analysis showed that patients treated with a target of 80-110 mg/dL had a lower risk of 30-day mortality compared with patients with a target of 90-140 mg/dL (odds ratio 0.65; 95% confidence interval, 0.43-0.98; P = .04).

These results advance the debate over appropriate blood glucose targets in critically ill patients, as they suggest that the effects of targeting blood glucose and the effects of severe hypoglycemia “can be separated,” the investigators wrote.

Current guidelines on intensive insulin therapy are based in part on findings of the NICE-SUGAR trial, which found that among adults treated in the ICU, intensive glucose control increased mortality. However, a post hoc analysis suggested the mortality increase in NICE-SUGAR was “largely driven by a significant incidence of moderate hypoglycemia, and to a greater degree severe hypoglycemia,” Dr. Hersh and his coauthors noted in their report.

“Given improvements in insulin delivery and glucose monitoring, a reassessment of potential benefits of [intensive insulin therapy] should once again be evaluated in a prospective randomized trial,” they wrote.

Dr. Hersh and his coauthors declared no financial or nonfinancial disclosures related to the study.

SOURCE: Hersh AM et al. CHEST 2018. doi: 10.1016/j.chest.2018.04.025.

In critically ill patients, treating blood glucose with a low target of 80-110 mg/dL was associated with a lower risk of 30-day mortality compared with patients with a target of 90-140 mg/dL, according to results of a retrospective cohort analysis.

With the computerized intravenous insulin protocol used in the study, the strict target could be achieved with a low rate of hypoglycemia, the authors wrote. The analysis was published in the journal CHEST^®.

monkeybusinessimages/Thinkstock

Unadjusted 30-day mortality was significantly lower in the 80-110–mg/dL group compared with the 90-140–mg/dL group (4.3% vs. 9.2%, respectively; P less than .001), according to the investigators.

Furthermore, logistic regression analysis showed that patients treated with a target of 80-110 mg/dL had a lower risk of 30-day mortality compared with patients with a target of 90-140 mg/dL (odds ratio 0.65; 95% confidence interval, 0.43-0.98; P = .04).

These results advance the debate over appropriate blood glucose targets in critically ill patients, as they suggest that the effects of targeting blood glucose and the effects of severe hypoglycemia “can be separated,” the investigators wrote.

Current guidelines on intensive insulin therapy are based in part on findings of the NICE-SUGAR trial, which found that among adults treated in the ICU, intensive glucose control increased mortality. However, a post hoc analysis suggested the mortality increase in NICE-SUGAR was “largely driven by a significant incidence of moderate hypoglycemia, and to a greater degree severe hypoglycemia,” Dr. Hersh and his coauthors noted in their report.

“Given improvements in insulin delivery and glucose monitoring, a reassessment of potential benefits of [intensive insulin therapy] should once again be evaluated in a prospective randomized trial,” they wrote.

Dr. Hersh and his coauthors declared no financial or nonfinancial disclosures related to the study.

SOURCE: Hersh AM et al. CHEST 2018. doi: 10.1016/j.chest.2018.04.025.

In critically ill patients, treating blood glucose with a low target of 80-110 mg/dL was associated with a lower risk of 30-day mortality compared with patients with a target of 90-140 mg/dL, according to results of a retrospective cohort analysis.

With the computerized intravenous insulin protocol used in the study, the strict target could be achieved with a low rate of hypoglycemia, the authors wrote. The analysis was published in the journal CHEST^®.

monkeybusinessimages/Thinkstock

Unadjusted 30-day mortality was significantly lower in the 80-110–mg/dL group compared with the 90-140–mg/dL group (4.3% vs. 9.2%, respectively; P less than .001), according to the investigators.

Furthermore, logistic regression analysis showed that patients treated with a target of 80-110 mg/dL had a lower risk of 30-day mortality compared with patients with a target of 90-140 mg/dL (odds ratio 0.65; 95% confidence interval, 0.43-0.98; P = .04).

These results advance the debate over appropriate blood glucose targets in critically ill patients, as they suggest that the effects of targeting blood glucose and the effects of severe hypoglycemia “can be separated,” the investigators wrote.

Current guidelines on intensive insulin therapy are based in part on findings of the NICE-SUGAR trial, which found that among adults treated in the ICU, intensive glucose control increased mortality. However, a post hoc analysis suggested the mortality increase in NICE-SUGAR was “largely driven by a significant incidence of moderate hypoglycemia, and to a greater degree severe hypoglycemia,” Dr. Hersh and his coauthors noted in their report.

“Given improvements in insulin delivery and glucose monitoring, a reassessment of potential benefits of [intensive insulin therapy] should once again be evaluated in a prospective randomized trial,” they wrote.

Dr. Hersh and his coauthors declared no financial or nonfinancial disclosures related to the study.

SOURCE: Hersh AM et al. CHEST 2018. doi: 10.1016/j.chest.2018.04.025.

DALLAS – An investigational device that couples laser spectroscopy with a machine-learning algorithm demonstrated a high sensitivity and specificity for discriminating skin cancers from benign lesions in real time, results from a single-center study showed.

“More than 5.4 million cases of nonmelanoma skin cancer were treated in 2012, but the accuracy of skin cancer screening prior to biopsy is pretty low, about 70%, and is individual dependent,” lead study author Sung Hyun Pyun, PhD, said at the annual conference of the American Society for Laser Medicine and Surgery. “There have been several in vivo skin cancer screening devices based on noninvasive techniques such as multispectral imaging, Raman spectroscopy, and electrical impedance spectroscopy, but their diagnostic accuracies were not sufficient for clinical use and could not be applied in real time.”

dbrunk@mdedge.com

DALLAS – An investigational device that couples laser spectroscopy with a machine-learning algorithm demonstrated a high sensitivity and specificity for discriminating skin cancers from benign lesions in real time, results from a single-center study showed.

“More than 5.4 million cases of nonmelanoma skin cancer were treated in 2012, but the accuracy of skin cancer screening prior to biopsy is pretty low, about 70%, and is individual dependent,” lead study author Sung Hyun Pyun, PhD, said at the annual conference of the American Society for Laser Medicine and Surgery. “There have been several in vivo skin cancer screening devices based on noninvasive techniques such as multispectral imaging, Raman spectroscopy, and electrical impedance spectroscopy, but their diagnostic accuracies were not sufficient for clinical use and could not be applied in real time.”

dbrunk@mdedge.com

DALLAS – An investigational device that couples laser spectroscopy with a machine-learning algorithm demonstrated a high sensitivity and specificity for discriminating skin cancers from benign lesions in real time, results from a single-center study showed.

“More than 5.4 million cases of nonmelanoma skin cancer were treated in 2012, but the accuracy of skin cancer screening prior to biopsy is pretty low, about 70%, and is individual dependent,” lead study author Sung Hyun Pyun, PhD, said at the annual conference of the American Society for Laser Medicine and Surgery. “There have been several in vivo skin cancer screening devices based on noninvasive techniques such as multispectral imaging, Raman spectroscopy, and electrical impedance spectroscopy, but their diagnostic accuracies were not sufficient for clinical use and could not be applied in real time.”

dbrunk@mdedge.com

A group of oncologists is urging the Food and Drug Administration to review a new, flat-pricing strategy for all doses of ibrutinib (Imbruvica), calling the shift potentially dangerous for patients.

Pharmacyclics, an AbbVie company based in Sunnyvale, Calif., recently introduced a new, single-tablet formulation of ibrutinib in varying strengths (140 mg, 280 mg, 420 mg, and 560 mg) and set a flat price across all doses. At the same time, they removed the drug’s original 140-mg capsules – which cost about a third of the new, flat-rate price – from the market. The drug company says the new, single-tablet formulations give patients a convenient, once-a-day dosing regimen that could improve therapy adherence.

Ibrutinib is approved to treat a number of hematologic cancers, including mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenstrom macroglobulinemia, and marginal zone lymphoma.

But in an April letter published in the Cancer Letter, nine physicians from cancer centers across the country expressed concern that the new dosage and pricing scheme could compromise patient safety and limit doctors’ dosage decisions.

“While the prescribing information is complex, prescribers and patients have had the flexibility of taking anywhere from one to four 140-mg capsules, readily permitting dose reduction to all but the lowest labeled dose [70 mg],” the authors wrote. “However, the new formulation and its associated marketing scheme [YOU&i] greatly impact the ability of the prescriber and patient to follow the prescribing information, resulting in the potential for a greatly enhanced risk of toxicities relative to that observed in the clinical trials which utilized multiples of the 140-mg capsules.”

The problems stem from a cancer drug that often requires dosage adjustments, the authors noted. The specific dosage for an ibrutinib patient depends on the indication, prior toxicities, concomitant medications, occurrence of ibrutinib intolerance, and current hepatic function. Because of such diverse criteria, dosage modifications are made frequently.

The new pricing system makes it harder for physicians to adjust the dose without running afoul of insurers and potentially affecting access for patients.

A group of oncologists is urging the Food and Drug Administration to review a new, flat-pricing strategy for all doses of ibrutinib (Imbruvica), calling the shift potentially dangerous for patients.

Pharmacyclics, an AbbVie company based in Sunnyvale, Calif., recently introduced a new, single-tablet formulation of ibrutinib in varying strengths (140 mg, 280 mg, 420 mg, and 560 mg) and set a flat price across all doses. At the same time, they removed the drug’s original 140-mg capsules – which cost about a third of the new, flat-rate price – from the market. The drug company says the new, single-tablet formulations give patients a convenient, once-a-day dosing regimen that could improve therapy adherence.

Ibrutinib is approved to treat a number of hematologic cancers, including mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenstrom macroglobulinemia, and marginal zone lymphoma.

But in an April letter published in the Cancer Letter, nine physicians from cancer centers across the country expressed concern that the new dosage and pricing scheme could compromise patient safety and limit doctors’ dosage decisions.

“While the prescribing information is complex, prescribers and patients have had the flexibility of taking anywhere from one to four 140-mg capsules, readily permitting dose reduction to all but the lowest labeled dose [70 mg],” the authors wrote. “However, the new formulation and its associated marketing scheme [YOU&i] greatly impact the ability of the prescriber and patient to follow the prescribing information, resulting in the potential for a greatly enhanced risk of toxicities relative to that observed in the clinical trials which utilized multiples of the 140-mg capsules.”

The problems stem from a cancer drug that often requires dosage adjustments, the authors noted. The specific dosage for an ibrutinib patient depends on the indication, prior toxicities, concomitant medications, occurrence of ibrutinib intolerance, and current hepatic function. Because of such diverse criteria, dosage modifications are made frequently.

The new pricing system makes it harder for physicians to adjust the dose without running afoul of insurers and potentially affecting access for patients.

A group of oncologists is urging the Food and Drug Administration to review a new, flat-pricing strategy for all doses of ibrutinib (Imbruvica), calling the shift potentially dangerous for patients.

Pharmacyclics, an AbbVie company based in Sunnyvale, Calif., recently introduced a new, single-tablet formulation of ibrutinib in varying strengths (140 mg, 280 mg, 420 mg, and 560 mg) and set a flat price across all doses. At the same time, they removed the drug’s original 140-mg capsules – which cost about a third of the new, flat-rate price – from the market. The drug company says the new, single-tablet formulations give patients a convenient, once-a-day dosing regimen that could improve therapy adherence.

Ibrutinib is approved to treat a number of hematologic cancers, including mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, Waldenstrom macroglobulinemia, and marginal zone lymphoma.

But in an April letter published in the Cancer Letter, nine physicians from cancer centers across the country expressed concern that the new dosage and pricing scheme could compromise patient safety and limit doctors’ dosage decisions.

“While the prescribing information is complex, prescribers and patients have had the flexibility of taking anywhere from one to four 140-mg capsules, readily permitting dose reduction to all but the lowest labeled dose [70 mg],” the authors wrote. “However, the new formulation and its associated marketing scheme [YOU&i] greatly impact the ability of the prescriber and patient to follow the prescribing information, resulting in the potential for a greatly enhanced risk of toxicities relative to that observed in the clinical trials which utilized multiples of the 140-mg capsules.”

The problems stem from a cancer drug that often requires dosage adjustments, the authors noted. The specific dosage for an ibrutinib patient depends on the indication, prior toxicities, concomitant medications, occurrence of ibrutinib intolerance, and current hepatic function. Because of such diverse criteria, dosage modifications are made frequently.

The new pricing system makes it harder for physicians to adjust the dose without running afoul of insurers and potentially affecting access for patients.