Periocular CO2 laser resurfacing: severe ocular complications from multiple unintentional laser impacts on the protective metal eye shields.

BACKGROUND AND OBJECTIVES: A 36-year-old woman underwent CO2 laser resurfacing for periocular rhytides using protective stainless steel Cox II ocular shields. Immediately after the treatment, corneal lesions were seen in both eyes. The left eye subsequent developed corneal ulceration and scarring, a deformed iris, cataract, and lower eye lashes showing signs of acute burns. The right cornea had a small inferior mid-peripheral superficial lesion and concomitant lower mid-peripheral burned eye lashes. Our objective was to determine the most likely cause of these ocular complications. STUDY: We estimated temperature-time combinations that could induce corneal injury and cataract. Heat conduction effects from a heated cornea to the lens and from a heated ring of periocular skin to the cornea were computed. The temperature response of a shield following CO2 laser irradiation was determined. RESULTS: We computed that cataract can develop when the corneal temperature reaches, for example, 80 °C for 14 seconds. A periocular ring of heated skin contributes little to the corneal temperature. After 7 pulses of consecutive CO2 laser bursts in 7.5 seconds, the total shield area already reached a homogeneous temperature of 63 °C. CONCLUSION: Despite uncertainties in procedural details and modeling of cataract temperatures, the eye injuries were caused beyond doubt by heating of tear-covered metal eye shields by at least 10 consecutive but unintentional laser impacts. Lasers Surg. Med. 50:980-986, 2018. © 2018 Wiley Periodicals, Inc.

Development of a non-melanoma skin cancer detection model.

BACKGROUND: The incidence and prevalence of skin cancer is rising. A detection model could support the (screening) process of diagnosing non-melanoma skin cancer. METHODS: A questionnaire was developed containing potential actinic keratosis (AK) and basal cell carcinoma (BCC) characteristics. Three nurses diagnosed 204 patients with a lesion suspicious of skin (pre)malignancy and filled in the questionnaire. Logistic regression analyses generated prediction models for AK and BCC. RESULTS: A prediction model containing nine characteristics correctly predicted the presence or absence of AK in 83.2% of the cases. BCC was predicted correctly in 91.4% of the cases by a model containing eight characteristics. The nurses correctly diagnosed AK in 88.3% and BCC in 90.9% of the cases. CONCLUSIONS: Detection or screening models for AK and BCC could be made with a limited number of variables. Nurses also diagnosed skin lesions correctly in a high percentage of cases. Further research is necessary to investigate the robustness of these findings, whether the percentage of correct diagnoses can be improved and how best to implement model-based prediction in the diagnostic process.

Ins and outs of endovenous laser ablation: afterthoughts.

Physicists and medical doctors "speak" different languages. Endovenous laser ablation (EVLA) is a good example in which technology is essential to guide the doctor to the final result: optimal treatment. However, for the doctor, it is by far insufficient just to turn on the knobs of the laser. He should understand what is going on in the varicose vein. On the other hand, the physicist is usually not aware what problems the doctor finds on his road towards improving a new technique. We have tried to bring both languages together in the special on Ins and outs of endovenous laser ablation published in this issue of Lasers in Medical Science. The 13 articles include endovenous related clinical (de Roos 2014; Kockaert and Nijsten 2014; van den Bos and Proebstle 2014) and socioeconomical articles (Kelleher et al 2014), the first paper on the molecular pathophysiologic mechanisms (Heger et al 2014), fiber tips (Stokbroekx et al 2014), the future of EVLA (Rabe 2014), a review of EVLA with some important issues for debate (Malskat et al 2014), an excellent paper on transcutaneous laser therapies of spider and small varicose veins (Meesters et al 2014), as well as several scientific modeling articles, varying from a mathematical model of EVLA that includes the carbonized blood layer on the fiber tip (van Ruijven et al 2014) and its application to the simulation of clinical conditions (Poluektova et al 2014) via experimental measurements of temperature profiles in response to EVLA, radiofrequency waves, and steam injections (Malskat et al 2014) to a literature review and novel physics approach of the absorption and particularly scattering properties of whole blood also including the infrared wavelengths used by EVLA (Bosschaart et al 2014). The aim of our afterthoughts, the 14th article in this special, is to try to amalgamate the clinical and physical contents of these contributions, providing the reader with the bridge that overlaps these different backgrounds.

Optical-thermal mathematical model for endovenous laser ablation of varicose veins.

Endovenous laser ablation (EVLA) is successfully used to treat varicose veins. However, the exact working mechanism is still not fully identified and the clinical procedure is not yet standardized. Mathematical modeling of EVLA could strongly improve our understanding of the influence of the various EVLA processes. The aim of this study is to combine Mordon's optical-thermal model with the presence of a strongly absorbing carbonized blood layer on the fiber tip. The model anatomy includes a cylindrically symmetric blood vessel surrounded by an infinite homogenous perivenous tissue. The optical fiber is located in the center of the vessel and is withdrawn with a pullback velocity. The fiber tip includes a small layer of strongly absorbing material, representing the layer of carbonized blood, which absorbs 45% of the emitted laser power. Heat transfer due to boiling bubbles is taken into account by increasing the heat conduction coefficient by a factor of 200 for temperatures above 95 °C. The temperature distribution in the blood, vessel wall, and surrounding medium is calculated from a numerical solution of the bioheat equation. The simulations were performed in MATLAB™ and validated with the aid of an analytical solution. The simulations showed, first, that laser wavelength did virtually not influence the simulated temperature profiles in blood and vessel wall, and, second, that temperatures of the carbonized blood layer varied slightly, from 952 to 1,104 °C. Our improved mathematical optical-thermal EVLA model confirmed previous predictions and experimental outcomes that laser wavelength is not an important EVLA parameter and that the fiber tip reaches exceedingly high temperatures.

Endovenous laser ablation (EVLA): a review of mechanisms, modeling outcomes, and issues for debate.

Endovenous laser ablation (EVLA) is a commonly used and very effective minimally invasive therapy to manage leg varicosities. Yet, and despite a clinical history of 16 years, no international consensus on a best treatment protocol has been reached so far. Evidence presented in this paper supports the opinion that insufficient knowledge of the underlying physics amongst frequent users could explain this shortcoming. In this review, we will examine the possible modes of action of EVLA, hoping that better understanding of EVLA-related physics stimulates critical appraisal of claims made concerning the efficacy of EVLA devices, and may advance identifying a best possible treatment protocol. Finally, physical arguments are presented to debate on long-standing, but often unfounded, clinical opinions and habits. This includes issues such as (1) the importance of laser power versus the lack of clinical relevance of laser energy (Joule) as used in Joule per centimeter vein length, i.e., in linear endovenous energy density (LEED), and Joule per square centimeter vein wall area, (2) the predicted effectiveness of a higher power and faster pullback velocity, (3) the irrelevance of whether laser light is absorbed by hemoglobin or water, and (4) the effectiveness of reducing the vein diameter during EVLA therapy.

Endovascular laser­tissue interactions and biological responses in relation to endovenous laser therapy.

Endovenous laser treatment (ELT) has evolved into a frequently employed modality for the treatment of leg varicose veins. Due to the very high complete response rates, minimal complications and side effects, and the possibility to monitor therapeutic outcome noninvasively by duplex ultrasound, a considerable amount of reports have been published on clinical and translational studies, whereas disproportionally few studies have been performed to elucidate the molecular and cellular basis for post-ELT vessel obliteration. Consequently, this review addresses the putative molecular and cellular mechanisms responsible for varicose vein obliteration following laser irradiation in the context of endovenous laser­tissue interactions. First, the histological profile of laser-treated varicose veins is summarized, and an account is given of the temporal and spatial dynamics of cells involved in inflammation and remodeling in the heat-affected vein segment. Inasmuch as thrombotic occlusion of the venous lumen blocks circulatory access to the affected vessel segment and thermal damage in the vascular wall causes most cells to die, the majority of cells involved in inflammation and remodeling have to be recruited. Second, the (possible) biochemical triggers for the chemotactic attraction of immune cells and fibroblasts are identified, comprising (1) thermal coagula, (2) thrombi, (3) dead and dying cells in the vein wall, and (4) thermally denatured extracellular matrix proteins in the vein wall. The molecular biology underlying the chemotactic signaling and subsequent obliterative remodeling is elucidated. Finally, the relative contribution of every biochemical trigger to obliterative remodeling is addressed.

Some controversies in endovenous laser ablation of varicose veins addressed by optical-thermal mathematical modeling.

Minimally invasive treatment of varicose veins by endovenous laser ablation (EVLA) becomes more and more popular. However, despite significant research efforts performed during the last years, there is still a lack of agreement regarding EVLA mechanisms and therapeutic strategies. The aim of this article is to address some of these controversies by utilizing optical-thermal mathematical modeling. Our model combines Mordon's light absorption-based optical-thermal model with the thermal consequences of the thin carbonized blood layer on the laser fiber tip that is heated up to temperatures of around 1,000 °C due to the absorption of about 45% of the laser light. Computations were made in MATLAB. Laser wavelengths included were 810, 840, 940, 980, 1,064, 1,320, 1,470, and 1,950 nm. We addressed (a) the effect of direct light absorption by the vein wall on temperature behavior, comparing computations by using normal and zero wall absorption; (b) the prediction of the influence of wavelength on the temperature behavior; (c) the effect of the hot carbonized blood layer surrounding the fiber tip on temperature behavior, comparing wall temperatures from using a hot fiber tip and one kept at room temperature; (d) the effect of blood emptying the vein, simulated by reducing the inside vein diameter from 3 down to 0.8 mm; (e) the contribution of absorbed light energy to the increase in total energy at the inner vein wall in the time period where the highest inner wall temperature was reached; (f) the effect of laser power and pullback velocity on wall temperature of a 2-mm inner diameter vein, at a power/velocity ratio of 30 J/cm at 1,470 nm; (g) a comparison of model outcomes and clinical findings of EVLA procedures at 810 nm, 11 W, and 1.25 mm/s, and 1,470 nm, 6 W, and 1 mm/s, respectively. Interestingly, our model predicts that the dominating mechanism for heating up the vein wall is not direct absorption of the laser light by the vein wall but, rather, heat flow to the vein wall and its subsequent temperature increase from two independent heat sources. The first is the exceedingly hot carbonized layer covering the fiber tip; the second is the hot blood surrounding the fiber tip, heated up by direct absorption of the laser light. Both mechanisms are about equally effective for all laser wavelengths. Therefore, our model concurs the finding of Vuylsteke and Mordon (Ann Vasc Surg 26:424-433, 2012) of more circumferential vein wall injury in veins (nearly) devoid of blood, but it does not support their proposed explanation of direct light absorption by the vein wall. Furthermore, EVLA appears to be a more efficient therapy by the combination of higher laser power and faster pullback velocity than by the inverse combination. Our findings suggest that 1,470 nm achieves the highest EVLA efficacy compared to the shorter wavelengths at all vein diameters considered. However, 1,950 nm of EVLA is more efficacious than 1,470 nm albeit only at very small inner vein diameters (smaller than about 1 mm, i.e., veins quite devoid of blood). Our model confirms the efficacy of both clinical procedures at 810 and 1,470 nm. In conclusion, our model simulations suggest that direct light absorption by the vein wall is relatively unimportant, despite being the supposed mechanism of action of EVLA that drove the introduction of new lasers with different wavelengths. Consequently, the presumed advantage of wavelengths targeting water rather than hemoglobin is flawed. Finally, the model predicts that EVLA therapy may be optimized by using 1,470 nm of laser light, emptying of the vein before treatment, and combining a higher laser power with a greater fiber tip pullback velocity.

Asymptomatic Infant Rib Fractures Are Primarily Non-abuse-Related and Should Not Be Used to Assess Physical Child Abuse.

Finding infant rib fractures was for many years an almost undisputed proof that physical child abuse took place. Yet, these rib fractures are virtually always occult and asymptomatic and are only identified when looked for, usually with X-rays, from physical child abuse accusations related to, e.g., suspicion of the shaken baby syndrome. In a recent systematic literature review (searched in Cochran, Embase, PubMed and Sociological Abstracts), Güvensel questioned the diagnostic accuracy of rib fractures to be caused by abuse, due to lack of sufficient scientific evidence. Further, there is currently a world-wide disagreement between physicians considering themselves child abuse specialized, and physicians that explore non-abuse-related symptoms that may mimic physical abuse, which, it is hoped, will significantly reduce current unjustified child abuse diagnoses. In an attempt to help resolving this disagreement, we hypothesize that the probability of physical child abuse-related infant rib fractures is significantly lower than the probability of all other possible non-abuse-related causes of occult asymptomatic infant rib fractures, e.g., from birth trauma, prematurity, osteogenesis imperfecta, hypermobile Ehlers-Danlos Syndrome, severe chronic placental pathology (e.g., massive perivillous fibrin depositions and severe chronic histiocytic intervillositis), and vitamin-D deficiency. As method, we attempted to assess the incidence of these various causes of infant rib fractures, in the Netherlands and the USA. The results are that the estimated Dutch and USA physical abuse-related infant rib fracture incidences are at least about 250 and 45 times lower than the sum of all the non-abuse-related estimates. Because these latter rib fractures are occult and asymptomatic, it is likely that (many) more could be out there. In conclusion, occult asymptomatic rib fractures develop perinatally, virtually always as birth trauma, in infants with sufficiently weak bones due to vitamin D deficiency, transmitted by their vitamin D deficient pregnant mothers. This group also includes cortical rib cracks due to deformation forces, with an estimated 186/100,000 incidence. And, despite obvious uncertainties in all estimated incidences, we provided strong evidence that our hypothesis has relevance, implying that the abundant occult asymptomatic rib fractures, when found in infants, should not be used to assess potential physical child abuse.

Child Abuse, Misdiagnosed by an Expertise Center-Part II-Misuse of Bayes' Theorem.

A newborn girl had, from two weeks on, small bruises on varying body locations, but not on her chest. Her Armenian grandmother easily bruised, too. Her mother was diagnosed with hypermobility-type Ehlers-Danlos-Syndrome (hEDS), an autosomal dominant connective tissue disorder, with a 50% inheritance probability. Referral to a University Medical Center located "Dutch Expertise Center for Child Abuse" resulted (prior to consultation) in physical abuse suspicion. Protocol-based skeletal X-rays showed three healed, asymptomatic rib fractures. A protocol-based Bayesian likelihood ratio guesstimation gave 10-100, erroneously used to suggest a 10-100 times likelier non-accidental-than-accidental cause. Foster care placement followed, even in a secret home, where she also bruised, suggesting hEDS inheritance. Correct non-accidental/accidental Bayes' probability of symptoms is (likelihood ratio) × (physical abuse incidence). From the literature, we derived an infant abuse incidence between about ≈0.0009 and ≈0.0026 and a likelihood ratio of <5 for bruises. For rib fractures, we used a zero likelihood ratio, arguing their cause was birth trauma from the extra delivery pressure on the chest, combined with fragile bones as the daughter of an hEDS-mother. We thus derived a negligible abuse/accidental probability between <5 × 0.0009 <0.005 and <5 × 0.0026 <0.013. The small abuse incidence implies that correctly using Bayes' theorem will also miss true infant physical abuse cases. Curiously, because likelihood ratios assess how more often symptoms develop if abuse did occur versus non-abuse, Bayes' theorem then implies a 100% infant abuse incidence (unwittingly) used by LECK. In conclusion, probabilities should never replace differential diagnostic procedures, the accepted medical method of care. Well-known from literature, supported by the present case, is that (child abuse pediatrics) physicians, child protection workers, and judges were unlikely to understand Bayesian statistics. Its use without statistics consultation should therefore not have occurred. Thus, Bayesian statistics, and certainly (misused) likelihood ratios, should never be applied in cases of physical child abuse suspicion. Finally, parental innocence follows from clarifying what could have caused the girl's bruises (inherited hEDS), and rib fractures (birth trauma from fragile bones).

Child Abuse, Misdiagnosed by an Expertise Center: Part I-Medico-Social Aspects.

Child abuse is a dangerous situation for an infant. Professionals need to weigh the risk of failing to act when children are seriously harmed against the serious harm done by carrying out safeguarding interventions. In severe cases, foster care might be advisable. The negative effects for the child's psychosocial development requires that such placement must be based on very solid evidence. Our aim is to identify why Dutch parents whose child may have a medical condition that could mimic symptoms of child abuse have a significant chance of being erroneously convicted and losing custody of their child. As a method, we describe and analyze the following case. An Armenian-Dutch newborn (uncomplicated term vaginal delivery), starting at two weeks after birth, developed small bruises on varying body locations. At two months, a Well-Baby Clinic physician referred the girl to a university hospital, mentioning that there were no reasons to suspect child abuse and that her Armenian grandmother easily bruised as well. However, before consultation by a pediatrician of the hospital-located Expertise Center for Child Abuse, the parents were suspected of child abuse. Based on the expertise center's protocols, skeletal X-rays were made, which showed three healed, asymptomatic rib fractures, while invalid statistics suggested, incorrectly, a 10-100 times more likely non-accidental than accidental cause of the symptoms (discussed in Part II of this series). The expertise enter physician ignored any argument that could show parental innocence, including the positive parent-child relationship reported by the Well-Baby Clinic and the general practitioner. The girl and her older brother were placed in a family foster home and then in a secret home. The case radically resolved when a large bruise also developed there, and an independent tissue disease specialist diagnosed a hereditary connective tissue disorder in the mother, implying that the girl's bruises and rib fractures could well be disease-related. In conclusion, if child abuse is suspected, and foster care placement considered, the patient and the parents should be thoroughly investigated by an independent experienced pediatrician together with an experienced pediatric clinical psychologist or psychotherapist to produce an independent opinion. Children deserve this extra safeguard before being separated from their parents.

Light fractionation significantly improves the response of superficial basal cell carcinoma to aminolaevulinic acid photodynamic therapy: five-year follow-up of a randomized, prospective trial.

Photodynamic therapy (PDT) using topical porphyrin-precursors is a promising treatment for superficial basal cell carcinoma (sBCC), but it needs further optimization. The aim of this study was to compare 5-year lesion (complete) response rates of sBCC treated with topical aminolaevulinic acid (ALA)-PDT using a single illumination vs. ALA-PDT using a 2-fold illumination scheme. A prospective, randomized study was performed, in which 91 patients with 299 lesions were treated with a 2-fold illumination scheme with 2 light fractions of 20 and 80 J/cm2 delivered 4 and 6 h after a single application of 20% ALA, and 106 patients with 274 lesions were treated with a single illumination of 75 J/cm2 4 h after a single application of 20% ALA. All lesions were treated at a fluence rate of 50 mW/cm2. An interim time to event analysis of complete response (CR) rates at 12 months showed encouraging results, and therefore lesions were followed for 5 years post-therapy. A third group of 50 patients with 172 lesions treated with 2-fold illumination were included after the initial period and analysed separately. The CR rate was significantly greater following the 2-fold illumination than the single illumination (p = 0.0002, log-rank test). Five years after therapy the CR rate after 2-fold illumination was 88%, whereas the CR rate after single illumination was 75%. The CR rate in the third group of lesions, treated with 2-fold illumination was 97% and 88% at 12 months and 5 years after therapy, respectively. Long-term follow-up indicates superior efficacy in sBCC of ALA-PDT with 2-fold illumination compared with ALA-PDT with single illumination.

PpIX fluorescence combined with auto-fluorescence is more accurate than PpIX fluorescence alone in fluorescence detection of non-melanoma skin cancer: an intra-patient direct comparison study.

BACKGROUND: Previous research on fluorescence detection of non-melanoma had mixed results. An accurate non-invasive method for the detection of skin cancer is valuable to dermatologists because of the high incidence of skin cancer among the aging population. One notable difference between the methods of fluorescence detection previously studied was the use of the auto-fluorescence of the skin. Currently, there has not been a direct comparison between both methods of fluorescence detection. OBJECTIVE: To compare the accuracy of PpIX fluorescence and auto-fluorescence normalized PpIX fluorescence detection systems for the localization non-melanoma skin cancers (NMSC). METHODS: We conducted an observer blinded direct comparison of both methods. Thirty patients, 14 females and16 males, mean age 62 (SD = 9 years), skin type I to III and being suspected of having one or more NMSC, visited an independent treatment centre for dermatology. The patients were investigated using a fluorescence detection system capable of both normalized and non-normalized PpIX fluorescence measurements. Liposomal encapsulated 5-aminolevulinic acid was used as a photosensitizer. For each area being investigated, the associated normalized and non-normalized fluorescence measurements were directly compared. The results of the analysis were confirmed by clinical investigation using a dermatoscope. Both methods were evaluated based on the number of true and false positives and the number of true and false negatives. Specificity and sensitivity were calculated. Statistical significance of the findings was determined using Pearson's Chi-squared test. RESULTS: The non-normalized method was found to have a sensitivity of 27 % and a specificity of 39 % and the normalized method has a sensitivity of 97% and a specificity of 100%. This difference is statistically significant (p < 0.05). CONCLUSION: Using auto-fluorescence in PpIX fluorescence detection of NMSC is more accurate that PpIX fluorescence detection alone.

Incidence, prevalence and future trends of primary basal cell carcinoma in the Netherlands.

Basal cell carcinoma (BCC) incidence rates are increasing worldwide. This study's objective was to estimate the occurrence of BCC in the Netherlands in terms of incidence and prevalence. Data on first primary carcinomas were retrieved from the Eindhoven Cancer Registry and extrapolated to the Dutch population. Extrapolated data showed a total of 444,131, histologically confirmed cases in the Netherlands between 1973 and 2008. During this period, age-adjusted incidence rates (European Standard Population) increased approximately three-fold from 40 to 148 per 100,000 in males and from 34 to 141 in females. Lifetime risk of BCC was 1 in 5-6 for Dutch citizens. Disease prevalence in the Netherlands was 1.4% and almost four times higher than this (5.4%) in the oldest age group (age 65 years or more). Predictions of future trends showed no signs of a plateau in the number of cases. These estimates should urge Dutch policymakers to provide solutions for the growing group of patients with BCC.

Cellular and molecular effects of pulsed dye laser and local narrow-band UVB therapy in psoriasis.

BACKGROUND AND OBJECTIVES: Pulsed dye laser (PDL) therapy is effective in clearing psoriasis plaques, but the mechanism of action is only partially understood. Local narrow-band ultraviolet B (NB-UVB), which has a better-defined mode of action, is an effective standard treatment for psoriasis. Our aim was to evaluate the cellular and molecular effects of PDL and to compare them with those of local NB-UVB in order to gain further insight into their mechanisms of action in psoriasis. STUDY DESIGN/PATIENTS AND METHODS: Nineteen patients with stable plaque-type psoriasis were treated either with PDL or NB-UVB. Lesional punch biopsies were obtained from all patients before treatment. Additional biopsies were obtained at 3 and 24 hours after PDL treatment in five of these patients. In 14 patients additional biopsies were taken after 7 and 13 weeks of treatment. Samples were histopathologically examined for the level of dermal T cell infiltrate, and the expression of epidermal beta-defensin 2, immune cell-derived tumor necrosis factor (TNF)-alpha, endothelial E-selectin, vascular endothelial growth factor receptor (VEGFR) 2 and 3, and the expression of interleukin (IL)-23 before and after treatment. RESULTS: The expression of VEGFR2, VEGFR3, and E-selectin was decreased in clinically high responders within 24 hours after PDL treatment. The expression of IL-23, TNF-alpha mRNA, and E-selectin protein were significantly reduced after two PDL treatments, whereas the expression of all epidermal markers and dermal T cell infiltrates had normalized after four treatments. The expression of epidermal activation markers and E-selectin were significantly reduced after 13 weeks of NB-UVB treatment. CONCLUSIONS: The expression of epidermal activation markers and the dermal T cell infiltrates were decreased after both treatments. The decreased expression of VEGFR2 and VEGFR3 followed by the down-regulation of TNF-alpha and IL-23p19 may be contributory factors in the efficacy of PDL in stable plaque-type psoriasis.

Assessing the public's preference for surgical treatment of primary basal cell carcinoma: a discrete-choice experiment in the south of the Netherlands.

BACKGROUND: Basal cell carcinoma (BCC) is a slowly growing nonmelanoma type of skin cancer that often is located on the face. Different therapies are available to treat BCC, of which surgical excision (SE) and Mohs micrographic surgery (MMS) are the most frequently used surgical procedures. OBJECTIVES: To examine which attributes of a surgical treatment the general public values as important and to determine the incremental willingness to pay for MMS versus SE. METHODS: A discrete-choice experiment (DCE) was conducted among members of the general public to examine which attributes of a surgical treatment for primary BCC are valued as important. In addition, based on the attributes included in the experiment, the willingness to pay for MMS versus SE was determined. RESULTS: Respondents (N=312) preferred a treatment with a lower recurrence rate, shorter surgery time, shorter travelling time, shorter waiting time, no risk for re-excision, and lower cost. The incremental willingness to pay for MMS was 847 euro ($1,203). CONCLUSIONS: Results from this DCE indicate that, when outcome and process attributes are considered from a societal perspective, MMS is preferred over SE for primary BCC. The authors have indicated no significant interest with commercial supporters.

Photodynamic therapy of acne vulgaris using 5-aminolevulinic acid 0.5% liposomal spray and intense pulsed light in combination with topical keratolytic agents.

BACKGROUND: Increasing antibiotic resistance of Propionibacterium acnes and growing awareness on the side effects of topical and systemic drugs in the treatment of acne vulgaris by physicians and patients have paved the way for a search into new efficacious and safe treatment modalities such as photodynamic therapy (PDT). Although the efficacy of PDT using 20% 5-aminolevulinic acid (ALA) cream has been established, phototoxic side effects limit its use. The 5-ALA concentration can be lowered by a factor of 40 by changing the vehicle of 5-ALA from a moisturizing cream to liposome encapsulation. OBJECTIVES: Assessment of the efficacy and the safety of PDT using 5-ALA 0.5% in liposomal spray and intense pulsed light (IPL) in combination with topical peeling agents (Li-PDT-PC) in acne vulgaris. MATERIALS AND METHODS: 32 patients suffering from acne participated in this randomized, prospective, single blind study. All patients were treated with Li-PDT-PC. During the study nine patients were additionally treated with topical or systemic antibiotics (Li-PDT-PC-AT). These patients were removed from the study although their results were recorded. Results After a mean period of 7.8 months and a mean number of 5.7 treatments the mean total number of lesions dropped from 34.6 lesions to 11.0 lesions, resulting in a mean improvement of 68.2%. Side effects were minimal. Additionally, an intention to treat analysis was conducted. CONCLUSION: Photodynamic therapy of acne vulgaris using 5-ALA 0.5% liposomal spray and IPL in combination with topical peeling agents is safe and efficacious, even in patients with acne recalcitrant to standard therapy.

Carbonized blood deposited on fibres during 810, 940 and 1,470 nm endovenous laser ablation: thickness and absorption by optical coherence tomography.

Endovenous laser ablation (EVLA) is commonly used to treat saphenous varicosities. Very high temperatures at the laser fibre tip have been reported during EVLA. We hypothesized that the laser irradiation deposits a layer of strongly absorbing carbonized blood of very high temperature on the fibre tip. We sought to prove the existence of these layers and study their properties by optical transmission, optical coherence tomography (OCT) and microscopy. We analysed 23 EVLA fibres, 8 used at 810 nm, 7 at 940 nm and 8 at 1,470 nm. We measured the transmission of these fibres in two wavelength bands (450-950 nm; 950-1,650 nm). We used 1,310 nm OCT to assess the thickness of the layers and the attenuation as a function of depth to determine the absorption coefficient. Microscopy was used to view the tip surface. All fibres showed a slightly increasing transmission with wavelength in the 450-950 nm band, and a virtually wavelength-independent transmission in the 950-1,650 nm band. OCT scans showed a thin layer deposited on all 13 fibres investigated, 6 used at 810 nm, 4 at 940 nm and 3 at 1,470 nm, some with inhomogeneities over the tip area. The average absorption coefficient of the 13 layers was 72 +/- 16 mm(-1). The average layer thickness estimated from the transmission and absorption measurements was 8.0 +/- 2.7 microm. From the OCT data, the average maximal thickness was 26 +/- 6 microm. Microscopy of three fibre tips, one for each EVLA wavelength, showed rough, cracked and sometimes seriously damaged tip surfaces. There was no clear correlation between the properties of the layers and the EVLA parameters such as wavelength, except for a positive correlation between layer thickness and total delivered energy. In conclusion, we found strong evidence that all EVLA procedures in blood filled veins deposit a heavily absorbing hot layer of carbonized blood on the fibre tip, with concomitant tip damage. This major EVLA mechanism is unlikely to have much wavelength dependence at similar delivered energies per centimetre of vein. Optical-thermal interaction between the vein wall and the transmitted laser light depends on wavelength.

The heat-pipe resembling action of boiling bubbles in endovenous laser ablation.

Endovenous laser ablation (EVLA) produces boiling bubbles emerging from pores within the hot fiber tip and traveling over a distal length of about 20 mm before condensing. This evaporation-condensation mechanism makes the vein act like a heat pipe, where very efficient heat transport maintains a constant temperature, the saturation temperature of 100 degrees C, over the volume where these non-condensing bubbles exist. During EVLA the above-mentioned observations indicate that a venous cylindrical volume with a length of about 20 mm is kept at 100 degrees C. Pullback velocities of a few mm/s then cause at least the upper part of the treated vein wall to remain close to 100 degrees C for a time sufficient to cause irreversible injury. In conclusion, we propose that the mechanism of action of boiling bubbles during EVLA is an efficient heat-pipe resembling way of heating of the vein wall.

Psoriasis may not be an independent predictor for the use of cardiovascular and anti-diabetic drugs: a 5-year prevalence study.

Most studies investigating the association between psoriasis and cardiovascular disease have shown a significant relationship. This comparison study investigated the association between psoriasis and prevalent use of cardiovascular drugs. Drug exposure data for 1998 to 2006 were extracted from the Dutch PHARMO-Record Linkage System database. Psoriasis patients were selected using an algorithm of hospitalization and drug dispensing records specific for psoriasis and matched with controls for gender, age and time-period. From the records of 2.5 million Dutch residents, 9,804 (0.4%) psoriasis patients and 15,288 (0.6%) controls were selected. Psoriasis patients used significantly more anti-hypertensives, anti-coagulant and anti-platelet agents, digoxin, nitrates, lipid-lowering and anti-diabetic drugs than the reference population during a 5-year period observation. In a multiple linear regression model adjusting for the number of unique drugs used, psoriasis was no longer significantly associated with any of these drug classes. Psoriasis patients used more cardiovascular-related drugs, but surveillance bias appears to affect this association considerably.

Fluorescence detection and diagnosis of non-melanoma skin cancer at an early stage.

BACKGROUND: The occurrence of non-melanoma skin cancer (NMSC), including actinic keratosis (AK) is increasing all over the world. The detection and diagnosis of NMSC is not optimal in clinical practice. Complementary methods for detection and accurate demarcation of NMSC at an early stage are needed in order to limit the damage caused by tumours. OBJECTIVE: The purpose of the present study was to use a large area skin fluorescence detection system to detect early NMSCs (clinical visible as well as non-visible lesions) in the face, neck, chest, back and hands of patients treated with UV and outdoor workers. METHODS: Fluorescence detection with a purpose-made digital camera and software (Dyaderm combined with 5-aminolevulinic acid (5-ALA) encapsulated in liposomes. RESULTS: In 93 consecutively referred patients positive skin fluorescence was detected in 61 patients. After histological examination the positive fluorescence appeared to be correlated to benign lesions in 28 patients (sebaceous gland hyperplasia in 22 patients) and to (pre-) malignant lesions in 33 patients (actinic keratosis in 29, BCC in 3 and SCC in 1 patient). False negative fluorescence was found in only one lesion. In five patients the FD technique used in this study appeared to be more sensitive for the identification of (pre-) malignant lesions than the clinical examination. This is in contrast with FD techniques used in previous studies. CONCLUSION: Diagnostic skin fluorescence using liposomal encapsulated 5-ALA and a specialised computerised detection and visualisation system offers the possibility for detection of NMSC at an early, pre-clinical stage. The technique is well suited to examine large areas of skin. It also identifies areas of most interest for performing confirmatory skin biopsies, as well as pre-operative assessment of boundaries of skin malignancies, and finally, the technique is applicable in the control and follow-up of skin cancer treatment.