Office-based transurethral devascularisation of low grade non-invasive urothelial cancer using diode laser. A feasibility study.

BACKGROUND AND OBJECTIVE: Frequent recurrence of non-muscle invasive bladder tumours (NMIBC) requiring transurethral resection of bladder tumour (TUR-BT) and lifelong monitoring makes the lifetime cost per patient the highest of all cancers. A new method is proposed for the removal of low grade NMIBCs in an office-based setting, without the need for sedation and pain control and where the patient can leave immediately after treatment. STUDY DESIGN/PATIENTS AND METHODS: An in vitro model was developed to examine the dose/response relationship between laser power, treatment time, and distance between laser fibre and target, using a 980 nm diode laser and chicken meat. The relationship between depth and extent of tissue destruction and the laser settings was measured using microscopy and non-parametric statistical analysis. A patient with low grade stage Ta tumour and multiple comorbidity, and therefore not fit for general anaesthesia, had a tumour devascularised using the laser at the tumour base, in the outpatient department. The tumour was left in the bladder. RESULTS: In the in vitro model, depth of tissue destruction increased with laser illumination up to 30 seconds, where median depth was 4.1 mm. With longer illumination the tissue destruction levelled off. The width of tissue destruction was 2-3 mm independent of laser illumination time. The in vivo laser treatments devascularised the tumour, which was later shed from the mucosa and passed out with the urine in the days following treatment. Pain score was 0 on a visual log scale (0-10). The tumour had completely disappeared two weeks after treatment. CONCLUSION: This diode laser technique may provide almost pain-free office-based treatment of low grade urothelial cancer using flexible cystoscopes in conscious patients. A prospective randomised study will be scheduled to compare the technique with standard TUR-BT in the operating theatre.

Fractional ablative erbium YAG laser: histological characterization of relationships between laser settings and micropore dimensions.

BACKGROUND AND OBJECTIVES: Treatment of a variety of skin disorders with ablative fractional lasers (AFXL) is driving the development of portable AFXLs. This study measures micropore dimensions produced by a small 2,940 nm AFXL using a variety of stacked pulses, and determines a model correlating laser parameters with tissue effects. MATERIALS AND METHODS: Ex vivo pig skin was exposed to a miniaturized 2,940 nm AFXL, spot size 225 µm, density 5%, power levels 1.15-2.22 W, pulse durations 50-225 microseconds, pulse repetition rates 100-500 Hz, and 2, 20, or 50 stacked pulses, resulting in pulse energies of 2.3-12.8 mJ/microbeam and total energy levels of 4.6-640 mJ/microchannel. Histological endpoints were ablation depth (AD), coagulation zone (CZ) and ablation width (AW). Data were logarithmically transformed if required prior to linear regression analyses. Results for histological endpoints were combined in a mathematical model. RESULTS: In 138 sections from 91 biopsies, AD ranged from 16 to a maximum of 1,348 µm and increased linearly with the logarithm of total energy delivered by stacked pulses, but also depended on variations in power, pulse duration, pulse repetition rate, and pulse energy (r(2) = 0.54-0.85, P < 0.0001). Microchannels deeper than 500 µm were created only by the highest pulse energy of 12.8 mJ/microbeam. Pulse stacking increased AD, and enlarged CZ and AW. CZ varied from 0 to 205 µm and increased linearly with total energy (r(2) = 0.56-0.75, P < 0.0001). AW ranged from 106 to 422 µm and increased linearly with the logarithm of number of stacked pulses (r(2) = 0.53-0.61, P < 0.001). The mathematical model estimated micropores of specific ADs with an associated range of CZs and AWs, for example, 300 µm ADs were associated with CZs from 27 to 73 µm and AWs from 190 to 347 µm. CONCLUSIONS: Pulse stacking with a small, low power 2,940 nm AFXL created reproducible shallow to deep micropores, and influenced micropore configuration. Mathematical modeling established relations between laser settings and micropore dimensions, which assists in choosing laser settings for desired tissue effects.

Fractional laser-assisted delivery of methyl aminolevulinate: Impact of laser channel depth and incubation time.

BACKGROUND AND OBJECTIVES: Pretreatment of skin with ablative fractional lasers (AFXL) enhances the uptake of topical photosensitizers used in photodynamic therapy (PDT). Distribution of photosensitizer into skin layers may depend on depth of laser channels and incubation time. This study evaluates whether depth of intradermal laser channels and incubation time may affect AFXL-assisted delivery of methyl aminolevulinate (MAL). MATERIALS AND METHODS: Yorkshire swine were treated with CO2 AFXL at energy levels of 37, 190, and 380 mJ/laser channel and subsequent application of MAL cream (Metvix) for 30, 60, 120, and 180 minutes incubation time. Fluorescence photography and fluorescence microscopy quantified MAL-induced porphyrin fluorescence (PpIX) at the skin surface and at five specific skin depths (120, 500, 1,000, 1,500, and 1,800 µm). RESULTS: Laser channels penetrated into superficial (∼300 µm), mid (∼1,400 µm), and deep dermis/upper subcutaneous fat layer (∼2,100 µm). Similar fluorescence intensities were induced at the skin surface and throughout skin layers independent of laser channel depth (180 minutes; P < 0.19). AFXL accelerated PpIX fluorescence from skin surface to deep dermis. After laser exposure and 60 minutes MAL incubation, surface fluorescence was significantly higher compared to intact, not laser-exposed skin at 180 minutes (AFXL-MAL 60 minutes vs. MAL 180 minutes, 69.16 a.u. vs. 23.49 a.u.; P < 0.01). Through all skin layers (120-1,800 µm), laser exposure and 120 minutes MAL incubation induced significantly higher fluorescence intensities in HF and dermis than non-laser exposed sites at 180 minutes (1,800 µm, AFXL-MAL 120 minutes vs. MAL 180 minutes, HF 14.76 a.u. vs. 6.69 a.u. and dermis 6.98 a.u. vs. 5.87 a.u.; P < 0.01). CONCLUSIONS: AFXL pretreatment accelerates PpIX accumulation, but intradermal depth of laser channels does not affect porphyrin accumulation. Further studies are required to examine these findings in clinical trials.

Fractional CO2 laser resurfacing for atrophic acne scars: a randomized controlled trial with blinded response evaluation.

BACKGROUND: The treatment of acne scars with fractional CO(2) lasers is gaining increasing impact, but has so far not been compared side-by-side to untreated control skin. OBJECTIVE: In a randomized controlled study to examine efficacy and adverse effects of fractional CO(2) laser resurfacing for atrophic acne scars compared to no treatment. METHODS: Patients (n = 13) with atrophic acne scars in two intra-individual areas of similar sizes and appearances were randomized to (i) three monthly fractional CO(2) laser treatments (MedArt 610; 12-14 W, 48-56 mJ/pulse, 13% density) and (ii) no treatment. Blinded on-site evaluations were performed by three physicians on 10-point scales. Endpoints were change in scar texture and atrophy, adverse effects, and patient satisfaction. RESULTS: Preoperatively, acne scars appeared with moderate to severe uneven texture (6.15 ± 1.23) and atrophy (5.72 ± 1.45) in both interventional and non-interventional control sites, P = 1. Postoperatively, lower scores of scar texture and atrophy were obtained at 1 month (scar texture 4.31 ± 1.33, P < 0.0001; atrophy 4.08 ± 1.38, P < 0.0001), at 3 months (scar texture 4.26 ± 1.97, P < 0.0001; atrophy 3.97 ± 2.08, P < 0.0001), and at 6 months (scar texture 3.89 ± 1.7, P < 0.0001; atrophy 3.56 ± 1.76, P < 0.0001). Patients were satisfied with treatments and evaluated scar texture to be mild or moderately improved. Adverse effects were minor. CONCLUSIONS: In this single-blinded randomized controlled trial we demonstrated that moderate to severe atrophic acne scars can be safely improved by ablative fractional CO(2) laser resurfacing. The use of higher energy levels might have improved the results and possibly also induced significant adverse effects.

The impact of treatment density and molecular weight for fractional laser-assisted drug delivery.

Ablative fractional lasers (AFXL) facilitate uptake of topically applied drugs by creating narrow open micro-channels into the skin, but there is limited information on optimal laser settings for delivery of specific molecules. The objective of this study was to investigate the impact of laser treatment density (% of skin occupied by channels) and molecular weight (MW) for fractional CO(2) laser-assisted drug delivery. AFXL substantially increased intra- and transcutaneous delivery of polyethylene glycols (PEGs) in a MW range from 240 to 4300 Da (Nuclear Magnetic Resonance, p<0.01). Increasing laser density from 1 to 20% resulted in augmented intra- and transdermal delivery (p<0.01), but densities higher than 1% resulted in reduced delivery per channel. Mass spectrometry indicated that larger molecules have greater intracutaneous retention than transcutaneous penetration. At 5% density, median delivery of PEGs with mean MW of 400, 1000, 2050 and 3350 Da were respectively 0.87, 0.31, 0.23 and 0.15 mg intracutaneously and 0.72, 0.20. 0.08 and 0.03 mg transcutaneously, giving a 5.8- and 24.0-fold higher intra- and transcutaneous delivery of PEG400 than PEG3350 (p<0.01). This study substantiates that fractional CO(2) laser treatment allows uptake of small and large molecules into and through human skin, and that laser density can be varied to optimize intracutaneous or transcutaneous delivery.

Hair removal.

Hair removal with optical devices has become a popular mainstream treatment that today is considered the most efficient method for the reduction of unwanted hair. Photothermal destruction of hair follicles constitutes the fundamental concept of hair removal with red and near-infrared wavelengths suitable for targeting follicular and hair shaft melanin: normal mode ruby laser (694 nm), normal mode alexandrite laser (755 nm), pulsed diode lasers (800, 810 nm), long-pulse Nd:YAG laser (1,064 nm), and intense pulsed light (IPL) sources (590-1,200 nm). The ideal patient has thick dark terminal hair, white skin, and a normal hormonal status. Currently, no method of lifelong permanent hair eradication is available, and it is important that patients have realistic expectations. Substantial evidence has been found for short-term hair removal efficacy of up to 6 months after treatment with the available systems. Evidence has been found for long-term hair removal efficacy beyond 6 months after repetitive treatments with alexandrite, diode, and long-pulse Nd:YAG lasers, whereas the current long-term evidence is sparse for IPL devices. Treatment parameters must be adjusted to patient skin type and chromophore. Longer wavelengths and cooling are safer for patients with darker skin types. Hair removal with lasers and IPL sources are generally safe treatment procedures when performed by properly educated operators. However, safety issues must be addressed since burns and adverse events do occur. New treatment procedures are evolving. Consumer-based treatments with portable home devices are rapidly evolving, and presently include low-level diode lasers and IPL devices.