Oon Tian Tan

Treatment of children with port-wine stains using the flashlamp-pulsed tunable dye laser.

Thirty-five children, three months to 14 years of age, with disfiguring port-wine stains were treated with a flashlamp-pulsed tunable dye laser. All had complete clearing of the stains after an average of 6.5 laser treatments to each lesional area; skin over bony prominences required approximately half as many sessions as skin on the cheek. Children less than seven years old required fewer sessions (mean +/- SD, 5.8 +/- 1.1) than older children (7.1 +/- 1.1; P less than 0.05). Treated skin was identical in texture and color to adjacent normal skin in 33 (94.3 percent) of the children, whereas 2 (5.7 percent) had small, isolated, depressed scars in areas accidentally traumatized soon after laser treatment. The only other side effect was transient hyperpigmentation, which occurred in 20 patients (57 percent). These results can be attributed to two distinguishing characteristics of the flashlamp-pulsed tunable dye laser: an emission wavelength of 577 nm, theoretically ideal for selective absorption by the intravascular target oxyhemoglobin, and a pulse duration of 360 microseconds, which closely matches the thermal relaxation time for dermal blood vessels and hence avoids diffuse nonspecific thermal necrosis with subsequent scarring of the treated skin.

Tunable Pulsed Dye Laser for the Treatment of Benign Cutaneous Vascular Ectasia

A tunable pulsed dye laser emitting at 577 nm and 360 microseconds pulse width was used to treat benign cutaneous vascular ectasias other than port wine stain in 77 patients. Except for leg telangiectasias (34 patients), the overall response was excellent. Forty-two of forty-five patients with hemangiomas, spider nevi, angioma serpiginosum, venous lakes or facial telangiectasias showed excellent results after 1-4 consecutive treatments. Scarring was observed in none of the patients. These results confirm previous data on the use of the tunable dye laser in the treatment of port wine stain, and suggest that 577 nm wavelength and 360 microseconds pulse width allow the selective photothermolysis of vascular cutaneous ectasias with better clinical results than previously reported.

RASA1 mutations and associated phenotypes in 68 families with capillary malformation-arteriovenous malformation

Capillary malformation–arteriovenous malformation (CM–AVM) is an autosomal‐dominant disorder, caused by heterozygous RASA1 mutations, and manifesting multifocal CMs and high risk for fast‐flow lesions. A limited number of patients have been reported, raising the question of the phenotypic borders. We identified new patients with a clinical diagnosis of CM–AVM, and patients with overlapping phenotypes. RASA1 was screened in 261 index patients with: CM–AVM (n = 100), common CM(s) (port‐wine stain; n = 100), Sturge–Weber syndrome (n = 37), or isolated AVM(s) (n = 24). Fifty‐eight distinct RASA1 mutations (43 novel) were identified in 68 index patients with CM–AVM and none in patients with other phenotypes. A novel clinical feature was identified: cutaneous zones of numerous small white pale halos with a central red spot. An additional question addressed in this study was the “second‐hit” hypothesis as a pathophysiological mechanism for CM–AVM. One tissue from a patient with a germline RASA1 mutation was available. The analysis of the tissue showed loss of the wild‐type RASA1 allele. In conclusion, mutations in RASA1 underscore the specific CM–AVM phenotype and the clinical diagnosis is based on identifying the characteristic CMs. The high incidence of fast‐flow lesions warrants careful clinical and radiologic examination, and regular follow‐up.

Removal of colored tattoos with the Q-switched alexandrite laser

The Q-switched alexandrite laser at 760 nm and 50- to 100-ns pulse duration has been shown to effectively remove blue-black as well as green, red, and mauve in seven human subjects with colored tattoos. An average of 9.0 treatments were required to completely remove the green pigment at an average fluence of 5.80 J/cm2 compared with an average of 9.7 treatments at an average fluence of 6.10 J/cm2 for red and an average of 10 treatments at an average fluence of 6.20 J/cm2 for mauve. Orange and yellow were unaffected by the alexandrite laser over a range of fluences tested.

Genetic Variants Associated with Port-Wine Stains

Background Port-wine stains (PWS) are capillary malformations, typically located in the dermis of the head and neck, affecting 0.3% of the population. Current theories suggest that port-wine stains are caused by somatic mutations that disrupt vascular development. Objectives Understanding PWS genetic determinants could provide insight into new treatments. Methods Our study used a custom next generation sequencing (NGS) panel and digital polymerase chain reaction to investigate genetic variants in 12 individuals with isolated port-wine stains. Importantly, affected and healthy skin tissue from the same individual were compared. A subtractive correction method was developed to eliminate background noise from NGS data. This allowed the detection of a very low level of mosaicism. Results A novel somatic variant GNAQ, c.547C>G, p.Arg183Gly was found in one case with 4% allele frequency. The previously reported GNAQ c.548G>A, p.Arg183Gln was confirmed in 9 of 12 cases with an allele frequency ranging from 1.73 to 7.42%. Digital polymerase chain reaction confirmed novel variants detected by next generation sequencing. Two novel somatic variants were also found in RASA1, although neither was predicted to be deleterious. Conclusions This is the second largest study on isolated, non-syndromic PWS. Our data suggest that GNAQ is the main genetic determinant in this condition. Moreover, isolated port-wine stains are distinct from capillary malformations seen in RASA1 disorders, which will be helpful in clinical evaluation.

Laser applications for benign oral lesions

Different subspecialists treat benign intraoral lesions using various approaches including surgical excision, medical therapy, sclerotherapy, and laser photocoagulation. The goal of this study was to establish whether lasers could effectively target and destroy oral lesions containing endogenous chromophores, while minimizing injury to unaffected adjacent tissues and critical structures.

Selective vascular coagulation of rabbit colon using a flashlamp-excited dye laser operating at 577 nanometers

Previous studies have demonstrated that brief pulses of selectively absorbed optical radiation can be used to confine thermal injury to pigmented targets within tissues. We performed studies in rabbits to assess the usefulness of this technique for selectively coagulating the colonic vasculature. By measuring the optical absorbance of rabbit colon with a spectrophotometer, it was determined that hemoglobin exhibits strong absorption relative to the rabbit colon at a wavelength of 577 nm. Because light must be absorbed to affect tissue, it was hypothesized that laser pulses of this wavelength would selectively damage blood vessels. This hypothesis was tested by examining the effect of 300-microseconds-long 577-nm laser pulses on rabbit colon in vivo. For delivered radiant exposures between 4 and 8 J/cm2, selective coagulation of the colonic vasculature could be produced without damage to the surrounding colon. At greater radiant exposures, vessel hemorrhage was occasionally noted but no transmural thermal injury was produced with delivered radiant exposures as high as 22 J/cm2. This technique may form the basis of a safe and simple treatment of vascular lesions of the colon such as angiodysplasia.

Quantitative three-dimensional assessment of port-wine stain clearance after laser treatments.

Outcomes analysis of laser treatment for port‐wine stains (PWS) has been hampered by the lack of an objective measure of surface area and volume; moreover, treatment success is often gauged by clinician subjective assessment. Three‐dimensional (3D) surface imaging has been applied in several medical disciplines to quantify surface changes, with promising results. We hypothesized that 3D surface imaging could be used to objectively measure changes in area and volume of PWS following laser treatment.

Quantitative three-dimensional assessment of port-wine stain clearance after laser treatments: OBJECTIVE ASSESSMENT OF PWS FOLLOWING LASER TREATMENTS

Outcomes analysis of laser treatment for port‐wine stains has been hampered by the lack of an objective measure of surface area and volume; moreover, treatment success is often gauged by clinician subjective assessment. Three‐dimensional (3D) surface imaging has been applied in several medical disciplines to quantify surface changes, with promising results. We hypothesized that 3D surface imaging could be used to objectively measure changes in area and volume of port‐wine stains following laser treatment.

Laser management of cutaneous pigmented lesions

Although important pioneering work in the laser treatment of medical conditions involving skin pigment started 15 years ago, the dominance of this modality has only emerged over this past decade. Keeping abreast of the field requires a broad perspective and understanding of the current applications, devices, techniques, and basic research.