From the Editors

It has been the intention of this thesis to increase the knowledge on the development of cutaneous side effects from treatment with the argon laser, the copper vapor laser, and the pulsed dye laser, which represent technical developments within laser systems used for treatment of vascular lesions. To reach that goal, the investigations focused on patient and lesional characteristics (skin pigmentation, skin redness, and epidermal thickness) and on the importance of UV irradiation before and after dermatological laser treatment. The aspect of UV irradiation was added because vascular lesions frequently involve the face and, therefore, may be exposed to sunlight in relation to laser treatment. Risk assessments were performed on clinically visible side effects in order to improve the preoperative information to the patients about their individual risks of obtaining side effects from dermatological laser treatment. The laser-induced side effects were evaluated by systematic clinical assessments, by histological and biochemical examinations, by skin reflectance measurements, optical profilometry, and ultrasonography. The term side effects is associated with both transient and permanent skin reactions such as purpura, wounds, textural changes, scars, pigmentary changes, and squamous cell carcinomas. Lightly pigmented, hairless hr/hr C3H/Tif mice, hairless, albino hr/hr MORO/Ibm mice, human, healthy volunteers, and children with port-wine stains were included in the studies. This thesis represents the first systematic and experimental approach to selected side effects from laser treatment of the skin. The argon laser (AL) and the copper vapor laser (CVL) The results from AL and CVL treatments are described together because these lasers are continuous/quasicontinuous lasers that do not meet the requirements for selective photothermolysis, which represents the most selective delivery of energy to cutaneous vessels. In normal-skinned human volunteers, the postoperative development of scars and pigmentary alterations depended on the preoperative constitutive skin pigmentation degree. Significant correlations were found between the preoperative skin pigmentation and the clinically scored pigmentary changes and scarring 1, 2, and 6 months postoperatively, indicating that dark-pigmented skin types respond with more heavy skin reactions than fair-pigmented skin types. Pigmentary changes occurred at lower intensity levels than scarring. No difference was seen between the AL and the CVL concerning the risk of inducing these side effects. In hairless, albino hr/hr MORO/Ibm mice increasing epidermal thicknesses reduced CVL-induced wounds and scars. Significant negative correlations were found between preoperative epidermal thicknesses and CVL-induced skin reactions. In lightly pigmented, hairless hr/hr C3H/Tif mice, CVL treatment induced an increase in skin pigmentation, evaluated by a semiquantitative technique. Postoperative UV irradiations with simulated solar UV increased the CVL-induced skin pigmentation additionally. The size of CVL-induced wounds and scars tended to enlarge by preoperative UV irradiations. In contrast, CVL-induced wounds were diminished and had a prolonged wound healing time when postoperative UV irradiations were given. This may indicate a deep constricted skin damage. Moreover, the histologically evaluated fibrosis and the frequency of bulging infiltration were increased by postoperative UV irradiation. When taking the liberty to extend the obtained results from the animal studies to humans, these results support the importance of pre- and postoperative sunprotection. Regarding skin cancer, in hairless mice it was found that one treatment with the CVL did not have a malignant potential itself. Pretreatment with the CVL at the highest intensity level (1.4W) delayed UV-induced photocarcinogenesis significantly. The pulsed dye laser (PDL) The PDL is described separately because it is the only laser in this thesis that fulf.

Background and Objective Laser therapy using the flashlamp-pumped pulsed dye laser (FPDL), along with contact cryotherapy, has proven to be an effective method with few side effects in the early treatment of superficial hemangiomas in infancy. The long-pulsed frequency-doubled Nd:YAG laser (VersaPulse®) is a new kind of laser whose efficacy and safety we examined in direct comparison with the FPDL. Study Design/Materials and Methods In a retrospective comparative study, we treated 50 infants with a total of 62 superficial hemangiomas. A total of 29 hemangiomas were treated with the FPDL (wavelength 585 nm, impulse duration 0.3–0.45 msec), 33 with the VersaPulse® (wavelength 532 nm, impulse duration 1–50 msec). Results With an average of 3.0 and 2.6 treatments (FPDL/VersaPulse® respectively), a cessation of growth or regressive tendency could be achieved in 93% and 70% of the hemangiomas, respectively. Complete regression occurred in 41% (FPDL) or 30% (VersaPulse®). Only in 7% (FPDL) or 18% (VersaPulse®) was there progression despite laser therapy. The side effect rates of both laser systems were low. Conclusion The FPDL has proven to be the slightly more effective treatment method in comparison and, therefore, remains the therapy of choice for the initial treatment. If parents wish to pursue further treatment in the regression phase of hemangiomas to optimize the cosmetic appearance, we recommend the VersaPulse® due to its low rates of side effects and painfulness. Lasers Surg. Med. 28:40–43, 2001. © 2001 Wiley-Liss, Inc.

Das Spektrum vaskulärer Hautveränderungen umfasst eine inhomogene Gruppe dermatologischer Erkrankungen. Neben Hämangiomen, Naevi flammei, Angiomen, Naevi aranei und primären/sekundären Teleangiektasien, die als klassische Indikationen für eine dermatologische Lasertherapie gelten, sind auch Besenreiser, die Rubeosis und venöse Malformationen Ziele der dermatologisch/ästhetischen Lasermedizin. Der früher häufig eingesetzte Argonlaser wurde in den 80er-Jahren durch den gepulsten Farbstofflaser abgelöst. Des Weiteren konnten sich der langgepulste KTP-Nd:YAG-Laser und in den letzten Jahren auch der langgepulste 1064nm-Nd:YAG-Laser durchsetzen. Diodenlaser sind in der Entwicklung und werden in der Zukunft sicher ihren Stellenwert finden. Die Kuperdampf-/Bromid- und Kryptonlaser haben in Deutschland keine weite Verbreitung finden können. Neben den gefäßspezifischen Lasern haben sich auch (IPL)-Intense-pulsed-light-Systeme etablieren können, auf die jedoch aus thematischen Gründen hier nicht weiter eingegangen werden soll. Das Ansprechen der jeweiligen Hautveränderung auf ein oder mehrere Lasersysteme wird im Wesentlichen vom Hauttyp sowie von der Tiefe und Größe der zugrunde liegenden Gefäße bestimmt. Die dermatologische Lasertherapie ist bei korrekter Diagnose- und Indikationsstellung sowie korrekter Durchführung eine nebenwirkungsarme und effektive Behandlungsoption.

Lasers in plastic surgery

Basal cell carcinoma occurring in port wine stain is extremely rare but has been reported after radiotherapy for port wine stain. The objective was to present 55-year-old man with a facial port wine stain who had multiple treatment sessions with both the argon laser and the pulsed dye laser and subsequently developed a recurrent multifocal basal cell carcinoma and highlight the treatment carried out and its effects on the outcome. We describe the history of the patient's port wine stain treatment, the development of skin cancer within it, and the different modalities of therapy carried out. The patient developed basal cell carcinoma in his port wine stain. The possibility of a causal link between laser treatment and this skin cancer was considered but it was discovered that he had had radiotherapy treatment of his birthmark at age 9. The basal cell carcinoma was successfully treated. This case of a clinically indistinct multifocal basal cell carcinoma arising within facial port wine stain was most likely due to previous radiotherapy treatment as a child, rather than laser treatment. Careful treatment history should identify such patients who should be followed-up for development of skin cancer.

Epidermal Damage and Limited Coagulation Depth with the Flashlamp-Pumped Pulsed Dye Laser: A Histochemical Study

Between June 1989 and December 1996, the flashlamp pumped pulsed dye laser was used to treat port wine stains (PWS) in 644 patients, age range 3 months-93 years (mean 21). The efficacy of the treatment was assessed after more than one year of follow-up. Each factor that might affect the efficacy was then evaluated statistically. Broad lesions required more laser treatments than narrow lesions and clearing tended to start from the periphery of the lesion, indicating the three-dimensional depth of the broader PWS. Patients who had been given previous treatments such as argon laser required about two more laser treatments than those who had not, but there were no clear differences in the efficacy of dye laser treatment between the two groups.

The standard wavelength in the treatment of port-wine stains (PWS) with the pulsed dye laser is 585 nm. In many cases, the response to therapy is not adequate despite many treatments, depending partly on vessels out of reach of the laser. Longer wavelengths penetrate deeper into the dermis, but are absorbed less by oxyhaemoglobin, and require higher fluences. In this study, 22 patients with PWS were treated with the flashlamp-pumped pulsed dye laser using two different wavelengths, 585 and 600 nm. Four adjacent sites with PWS were treated on one occasion with 585 nm, 600 nm and equal fluence, and with 1.5 and 2 times the 585 nm fluence. The test areas were examined blindly, by four evaluators, an average of 12.5 weeks later. There was significantly less lightening with 600 nm than with 585 nm (P < or = 0.001) when equal fluences were used. When 1.5 and 2 times the 585 nm fluence were applied, with 600 nm the lightening was equal to that after 585 nm. However, in individual cases (11 of 22) 600 nm showed a superior lightening of at least 20% compared to 585 nm. There was slight hyperpigmentation and hypopigmentation, but no atrophy or scarring. In conclusion, 585 nm remains the wavelength of choice in treatment of PWS with the pulsed dye laser. However, in cases that do not respond satisfactorily with 585 nm, it may be worth trying 600 nm with a fluence that is at least 1.5-2 times the 585 nm fluence.

Neither the pathogenesis of port wine stain (PWS) birthmarks nor tissue effects of pulsed dye laser (PDL) treatment of these lesions is fully understood. There are few published reports utilizing gene expression analysis in human PWS skin. We aim to compare gene expression in PWS before and after PDL, using DNA microarrays that represent most, if not all, human genes to obtain comprehensive molecular profiles of PWS lesions and PDL-associated tissue effects. Five human subjects had PDL treatment of their PWS. One week later, three biopsies were taken from each subject: normal skin (N); untreated PWS (PWS); PWS post-PDL (PWS + PDL). Samples included two lower extremity lesions, two facial lesions, and one facial nodule. High-quality total RNA isolated from skin biopsies was processed and applied to Affymetrix Human gene 1.0ST microarrays for gene expression analysis. We performed a 16 pair-wise comparison identifying either up- or down-regulated genes between N versus PWS and PWS versus PWS + PDL for four of the donor samples. The PWS nodule (nPWS) was analyzed separately. There was significant variation in gene expression profiles between individuals. By doing pair-wise comparisons between samples taken from the same donor, we were able to identify genes that may participate in the formation of PWS lesions and PDL tissue effects. Genes associated with immune, epidermal, and lipid metabolism were up-regulated in PWS skin. The nPWS exhibited more profound differences in gene expression than the rest of the samples, with significant differential expression of genes associated with angiogenesis, tumorigenesis, and inflammation. In summary, gene expression profiles from N, PWS, and PWS + PDL demonstrated significant variation within samples from the same donor and between donors. By doing pair-wise comparisons between samples taken from the same donor and comparing these results between donors, we were able to identify genes that may participate in formation of PWS and PDL effects. Our preliminary results indicate changes in gene expression of angiogenesis-related genes, suggesting that dysregulation of angiogenic signals and/or components may contribute to PWS pathology.

Lasers have been the treatment of choice for Port-wine stain (PWS). However, only one type of laser is not a panacea for all PWS malformations. This is may be due to the great heterogeneity of phenotypic presentation of this congenital anomaly as color, depth, and the site of the lesion. For the treatment of PWS, flash lamp-pumped pulsed dye laser, carbon dioxide, argon, krypton, copper bromide, frequency-doubled neodymium:yttrium-aluminum-garnet (Nd:YAG), and also intense pulsed light sources can be used. To assess and compare the effectiveness of wavelength 532 and 1,064 nanometers (nm) long pulse Nd:YAG laser in the treatment of facial port-wine stain. This was a comparative therapeutic study for the treatment of facial port-wine stain. We divided the lesion into two halves, medial and lateral, and then each half was treated by 532 or 1,064 nm Nd:YAG. The sessions were done every 4 weeks for six sessions and follow-up after 3 months, then assess the response before and after the sessions and at the end follow-up period objectively (degree of improvement, Photo comparison) and subjectively (Patient satisfaction). Fourteen out of nineteen patients completed all sessions of the treatment, and the other five patients were defaulted from the study due to different causes, including marriage, poor compliance for treatment, and for unknown causes. They were 13 (92.85%) females and 1 (7.15%) male. The mean age of patients was 22.07 ± 9.003 years (range 8-44 years). Three patients (21.4%) were Fitzpatrick's skin type III and four patients (78.6%) were typed IV. There was no hypertrophy in any of the lesions. All facial PWSs lie along the distribution of the trigeminal nerve. Four patients (28.6%) have V1 (ophthalmic), 12 patients (85.7%) have V2 (maxillary), and 9 (64.3%) have V3 (mandibular). The color of PWSs was pink-red in eight patients (57.1%), dark-red in four patients (28.6%), and purple-dark two patients (14.3%). The improvement score for the halves of the PWS treated with long pulsed Nd:YAG 532 nm were: failure = 0%, mild = 14.3%, moderate = 28.6%, good = 28.6%, excellent = 28.6%, while the score for long pulsed Nd:YAG 1,064 nm were: failure = 7.1%, mild = 85.7%, moderate = 7.1%, good = 0%, excellent = 0%. There are highly significant differences between the two parameters (P-value = <0.001). The visual analog scale regarding the halves of PWS treated by long pulsed Nd:YAG 532 nm before the treatment was 5.00 ± 0.96 and after treatment was 2.28 ± 1.43. There is a highly significant difference between the two scores (P-value <0.001). The visual analog scale for the halves of PWS before the use of long pulsed Nd:YAG 1,064 nm was 5.14 ± 0.77 and after treatment was 3.71 ± 0.82. There is a highly significant difference between the two scores (P-value <0.001). At the end of follow-up period, mean score ± SD for 532 nm was 2.28 ± 1.43 and for 1,064 nm was 3.71 ± 0.82. There is a highly significant difference in both wavelengths, when compared with scores for each before the treatment. In comparison, between 532 and 1,064 nm, the difference in the visual analog scale for 532 nm before and at the end of the follow-up period was 2.7143 ± 1.069, while for 1,064 nm was 1.4286 ± 0.513. There is a highly significant difference between the two wavelengths (P-value <0.001). The mean score for the satisfaction of long pulsed Nd:YAG 532 nm was 76 ± 23, while for 1,064 nm was 33 ± 8, so there is a highly significant difference between the two parameters (P-value = <0.001). None of the patients showed recurrence, scar, or hyperpigmentation after 3 months of the last treatment session. One patient developed hyperpigmentation that resolved with hydroquinone cream 4% and no scarring was seen at the end of follow-up period. The long pulsed Nd:YAG laser 532 nm is more effective in the treatment of superficial bright red facial PWSs than the long pulse Nd:YAG 1,064 nm. More treatment sessions may lead to better clearance of the lesions. The use of non-invasive imaging technique such as dermoscopy, skin analyzer likes spatial frequency domain imaging (SFDI) device, or confocal microscopy to assess the level of malformations and the changes before and after the treatment with each type can give a clearer view of tissue response to laser irradiation. Lasers Surg. Med. 48:852-858, 2016. © 2016 Wiley Periodicals, Inc.

Background: Laser iridotomy is the established treatment for angle-closure glaucoma. Nd:YAG (neodymium: yttrium–aluminium–garnet) laser iridotomy is challenging in the heavily pigmented irides of African and Asian patients, Aim: To present...

The 585 nm flashlamp-pumped pulsed (FLPP) dye laser is an effective and established treatment for port-wine stains (PWSs) during childhood. Unfortunately, PWSs tend to darken in color and may thicken or develop nodules as the lesions age, thereby making treatment difficult in adult patients since they may require several laser sessions producing unpredictable results. The aim of this article is to present and discuss the results obtained in four adult patients with PWS by use of a new approach in FLPP dye laser treatment. The goal of this technique was to damage, during the same treatment, the lesions at both deep and superficial levels and to reduce the number of laser sessions required to obtain the most effective eradication of hypertrophied PWSs. Four patients (two men and two women aged 54, 57, 49, and 61, respectively) were referred for treatment of congenital hypertrophied PWS of the face. Every dye laser session consisted of two laser passes. During the first pass the wavelength ranged from 590 to 600 nm with a long pulse (1.500 microseconds), while the second pass was performed utilizing the classic short pulse (450 microseconds) and wavelength (585 nm). Successive treatments were performed at 6- to 8-week intervals. All four patients had a complete clearing of their PWS after a number of treatments, ranging from three to five sessions. Three of them (one man and the two women) experienced extremely mild blistering in a limited small area that healed in approximately 10 days without scarring. The laser sessions were well tolerated by all patients. None of the patients developed atrophic or hypertrophied scars or dyschromia. Our results show an excellent response in all patients with just a few treatments (three to five sessions) and, in spite of two passes, only mild side effects that are probably limited due to cooling of the skin. We also observed a flattening and reduction of the nodules.

Although pulsed dye laser (PDL) treatment of port-wine stain (PWS) has long been proven safe and effective, incomplete clearance of these vascular malformations can be problematic. In addition, advanced PWS with deeper coloration and tissue hypertrophy can be particularly difficult to treat because of the superficial dermal penetration of 585- to 595-nm light. The purpose of this study was to evaluate the safety and efficacy of a novel device that delivers sequential pulses of 595- and 1,064-nm wavelengths in the treatment of recalcitrant and hypertrophic PWS. Twenty-five children and adults (skin phototypes I-III) with recalcitrant or hypertrophic PWS showing incomplete clearance after 10 prior PDL treatments were included in the study. Successive treatments using a 595-nm PDL and a 1,064-nm neodymium-doped yttrium-aluminum-garnet (Nd:YAG) laser were delivered at 6- to 8-week intervals. Two masked assessors determined clinical improvement of treatment areas using independent evaluation of comparative photographs at baseline and 3 months after treatment using a standard quartile grading scale. The use of dual 595-/1,064-nm wavelengths provided continued improvement of PWS that were previously recalcitrant to ongoing PDL therapy. Side effects were limited to transient erythema, edema, and mild purpura. Rare vesicle formation was observed, with no subsequent scarring or undesirable pigmentary changes. The novel dual 595-nm PDL and 1,064-nm Nd:YAG laser is an effective treatment for PWS that are recalcitrant to PDL therapy alone.

• Strawberry, or capillary, hemangiomas are common vascular neoplasms, with an incidence of approximately 2.6% in neonates. They usually develop in the first few weeks of life, so that between 1 month and 1 year the incidence rises to between 8.7% and 10.1%. These lesions may grow quite large in the first year of life, and they may ulcerate or obstruct a vital organ or function. The great majority will spontaneously regress after the first year of life. Parents are often alarmed at the sight of these hemangiomas and need reassurance that the great majority will regress spontaneously. Treatments such as cryosurgery, irradiation, radium instillation, corticosteroid therapy, or surgical excision are often ineffective or cause significant morbidity. We describe 10 children with capillary hemangiomas treated with the flash lamp—pumped pulsed dye laser. The patients ranged in age from 7 weeks to 5.5 years at the beginning of laser therapy. The patients underwent 3.1 ± 1 (mean ± SD) laser treatments, with a mean regression of the lesions of 69.9% ±4.5%. All patients demonstrated some diminution in the size and color of their hemangiomas after the treatments, and there were no ill effects, such as ulceration, hemorrhage, infection, or scarring. There was no evidence of hyperpigmentation or hypopigmentation. Pulsed dye laser therapy should be considered as an option in the treatment of capillary hemangiomas, preferably prior to their full evolution. It is also a useful therapeutic approach in those hemangiomas that are slow to regress in older children. (<i>Arch Dermatol.</i>1991;127:202-205)

The copper vapour laser has in theory qualities which make it interesting in the treatment of cutaneous vascular malformations. In order to study the clinical effect of the copper vapour laser and to compare its effect with the effect of the argon laser, we treated 38 patients with port-wine stain or facial telangiectasia with the copper vapour laser. Thirty-one patients were evaluated and of these 24 were improved or much improved. Nineteen patients had previously been treated with the argon laser, and in this group the copper vapour laser had better effect than the argon laser in 8 patients and equal effect in 9 patients. In 7 patients side-effects like scarring or hyperpigmentation were noted after treatment with copper vapour laser.