Publications by authors named "Ellen de Haas"

25 Publications

  • Page 1 of 1

[Melanocytic tumour of uncertain malignant potential; practical dilemmas].

Ned Tijdschr Geneeskd 2019 07 5;163. Epub 2019 Jul 5.

DermaPark, Uden.

Background: 'MELTUMP' (melanocytic tumour of uncertain malignant potential) is a collective category for different melanocytic tumours in which the diagnosis 'melanoma' cannot be demonstrated, but equally cannot be excluded. Since the malignant potential of these disorders is unpredictable, there is no singular approach.

Case Description: A 48-year-old woman attended a dermatology clinic for an atypical mole on the left lower leg. Her medical history included two previous melanomas. The mole was photographed and excised. Histopathological diagnostics showed atypical melanocytic proliferation; the abnormality was classified as a MELTUMP. Based on the photo of the mole, it was decided to perform a re-excision with a margin of 5 mm.

Conclusion: It is recommended to obtain photographic evidence for each pigmented abnormality that is suspected of being malignant. Based on this photo, a clinical suspicion of melanoma can be assessed later. Particularly for MELTUMP patients this can be useful when determining the clinical management.
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July 2019

Recommendations for the Optimal Radiation Dose in Patients With Primary Cutaneous Anaplastic Large Cell Lymphoma: A Report of the Dutch Cutaneous Lymphoma Group.

Int J Radiat Oncol Biol Phys 2017 12 24;99(5):1279-1285. Epub 2017 Aug 24.

Department of Dermatology, Leiden University Medical Center, Leiden, The Netherlands.

Purpose: To determine the optimal radiation dose for treatment of primary cutaneous anaplastic large cell lymphoma (C-ALCL) with solitary or localized, multifocal or recurrent skin lesions.

Methods And Materials: In this multicenter study, patients with C-ALCL who had been treated with radiation therapy (RT) between 1984 and 2016 were retrieved from the Dutch registry of cutaneous lymphomas. Distinction was made between patients first presenting with solitary or localized lesions (n=63), with multifocal skin lesions (n=6), and patients with a skin relapse (n=22). Radiation doses, treatment response, and follow-up were evaluated. Radiation doses were categorized as low-dose (≤20 Gy), intermediate-dose (21-39 Gy), and high-dose (≥40 Gy) RT.

Results: Of 63 patients presenting with solitary or localized skin lesions, 61 (97%) showed a complete response (CR). There were no differences in CR between low-dose (16 of 17), intermediate-dose (15 of 15), and high-dose RT (30 of 31). After a median follow-up of 46 months, 30 of 63 patients (48%) had a relapse, but in-field relapses were never observed. Six of 6 patients (100%) initially presenting with multifocal skin lesions showed a CR (3 of 3 low-dose, 2 of 2 intermediate-dose, 1 of 1 high-dose RT). After a median follow-up of 27 months, 3 of 6 patients had a relapse. Treatment of 33 skin relapses in 22 patients showed no differences in CR between low-dose (18 of 19), intermediate-dose (6 of 6), and high-dose RT (8 of 8). In the last 10 years there has been a decrease in radiation dose used in the treatment of C-ALCL. Treatment of multifocal and recurrent lesions with a dose of 8 Gy (2 × 4 Gy) resulted in CR of 17 of 18 lesions.

Conclusions: Our results show that a radiation dose of 20 Gy (8 × 2.5 Gy) is effective in patients presenting with solitary or localized skin lesions. For patients with multifocal skin lesions and patients with a skin relapse, a dose of 8 Gy (2 × 4 Gy) may be sufficient.
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http://dx.doi.org/10.1016/j.ijrobp.2017.08.010DOI Listing
December 2017

Clinical Staging and Prognostic Factors in Folliculotropic Mycosis Fungoides.

JAMA Dermatol 2016 09;152(9):992-1000

Department of Dermatology, Leiden University Medical Center, the Netherlands.

Importance: Large case series suggest that patients with folliculotropic mycosis fungoides (FMF) have a worse prognosis than patients with classic mycosis fungoides (MF). However, recent studies described a subgroup of patients with FMF with a more favorable prognosis. Distinction between indolent and aggressive FMF may have important therapeutic consequences but is hampered by the inability of the current tumor-node-metastasis-blood (TNMB) staging system to classify patients with FMF in a clinically meaningful way.

Objective: To differentiate between indolent and aggressive FMF using clinicopathological criteria and to define prognostic factors in patients with FMF.

Design, Setting, And Participants: In this prospective cohort study, we followed 203 patients with FMF, included in the Dutch Cutaneous Lymphoma Registry between October 1985 and May 2014 at a tertiary referral center hosting the Dutch Cutaneous Lymphoma Registry. Overall, 220 patients with FMF had been registered, but 17 patients with incomplete follow-up data or a history of classic MF were excluded.

Main Outcomes And Measures: Main outcomes included clinical and histological characteristics, disease progression, and survival. Prognostic factors were investigated using Cox proportional hazard regression analysis. Distinction between early plaque-stage FMF and advanced plaque-stage FMF was made by a blinded review of skin biopsy specimens from patients presenting with plaques.

Results: In a cohort of 147 men and 56 women (median [range] age, 59 [15-93] years), patients with histologically early plaque-stage FMF had a very similar overall survival (OS) rate to patients with only patches and/or follicular papules (10-year OS, 71% vs 80%), while the survival rate of patients with histologically advanced plaque-stage FMF was almost identical to that of patients presenting with tumors (10-year OS, 25% vs 27%). Subsequently, 3 clinical subgroups with significantly different survival data were distinguished: early skin-limited FMF (group A; n = 84; 5-year and 10-year OS, 92% and 72%); advanced skin-limited FMF (group B; n = 102; 5-year and 10-year OS, 55% and 28%); and FMF presenting with extracutaneous disease (group C; n = 17; 5-year and 10-year OS, 23% and 2%). Age at diagnosis, large cell transformation and secondary bacterial infection were independent risk factors for disease progression and/or poor survival.

Conclusions And Relevance: The results of this study provide useful criteria to differentiate between indolent and aggressive FMF and confirm the existence of a subgroup of FMF with a favorable prognosis.
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http://dx.doi.org/10.1001/jamadermatol.2016.1597DOI Listing
September 2016

Light Fractionation Significantly Increases the Efficacy of Photodynamic Therapy Using BF-200 ALA in Normal Mouse Skin.

PLoS One 2016 12;11(2):e0148850. Epub 2016 Feb 12.

Center for Optical Diagnostics and Therapy, Department of Otolaryngology and Head & Neck Surgery, Erasmus MC, Rotterdam, The Netherlands.

Background: Light fractionation significantly increases the efficacy of 5-aminolevulinic acid (ALA) based photodynamic therapy (PDT) using the nano-emulsion based gel formulation BF-200. PDT using BF-200 ALA has recently been clinically approved and is under investigation in several phase III trials for the treatment of actinic keratosis. This study is the first to compare BF-200 ALA with ALA in preclinical models.

Results: In hairless mouse skin there is no difference in the temporal and spatial distribution of protoporphyrin IX determined by superficial imaging and fluorescence microscopy in frozen sections. In the skin-fold chamber model, BF-200 ALA leads to more PpIX fluorescence at depth in the skin compared to ALA suggesting an enhanced penetration of BF-200 ALA. Light fractionated PDT after BF-200 ALA application results in significantly more visual skin damage following PDT compared to a single illumination. Both ALA formulations show the same visual skin damage, rate of photobleaching and change in vascular volume immediately after PDT. Fluorescence immunohistochemical imaging shows loss of VE-cadherin in the vasculature at day 1 post PDT which is greater after BF-200 ALA compared to ALA and more profound after light fractionation compared to a single illumination.

Discussion: The present study illustrates the clinical potential of light fractionated PDT using BF-200 ALA for enhancing PDT efficacy in (pre-) malignant skin conditions such as basal cell carcinoma and vulval intraepithelial neoplasia and its application in other lesion such as cervical intraepithelial neoplasia and oral squamous cell carcinoma where current approaches have limited efficacy.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0148850PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4752243PMC
July 2016

Effective Single Photodynamic Treatment of Onychomycosis Using a Multifunctional Porphyrin Photosensitizer and Green Light.

J Fungi (Basel) 2015 Jul 27;1(2):138-153. Epub 2015 Jul 27.

Department of Radiotherapy, Erasmus Medical Centre, P.O. Box 2040, Office Ee-1683, 3000-CA Rotterdam, The Netherlands.

Onychomycosis is predominantly caused by the dermatophytes , and The main treatment obstacle concerns low nail-plate drug permeability. antifungal photodynamic treatment (PDT) and nail penetration enhancing effectiveness have been proven for multifunctional photosensitizer 5,10,15-(4--methylpyridinium)-20-(4-(butyramido-methylcysteinyl)-hydroxyphenyl)-[21,23]-porphine trichloride (PORTHE). This study investigates single PORTHE green laser/LED PDT of varying degrees of onychomycoses in a human nail model. , , onychomycoses were induced on nail pieces at 28 °C (normal air) and 37 °C (6.4% CO₂) during 3 to 35 days and PDTs applied to the 37 °C infections. All dermatophytes showed increasingly nail plate invasion at 37 °C between 7 and 35 days; arthroconidia were observed after 35 days for and . Using 81 J/cm² (532 nm) 7-day onychomycoses were cured (92%) with 80 µM PORTHE (pH 8) after 24 h propylene glycol (PG, 40%) pre-treatment and 35-day onychomycoses (52%-67%) with 24 h PORTHE (40-80 µM)/40% PG treatment (pH 5). 28 J/cm² LED light (525 ± 37 nm) improved cure rates to 72%, 83% and 73% for, respectively, , and 35-day onychomycoses and to 100% after double PDT. Data indicate PDT relevance for onychomycosis.
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http://dx.doi.org/10.3390/jof1020138DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5753106PMC
July 2015

A Retrospective Review of Reconstructive Options and Outcomes of 202 Cases Large Facial Mohs Micrographic Surgical Defects, Based on the Aesthetic Unit Involved.

J Cutan Med Surg 2015 Nov-Dec;19(6):580-7. Epub 2015 May 18.

Department of Plastic and Reconstructive Surgery, Erasmus University Medical Center Rotterdam, The Netherlands

Background: For optimal treatment of facial defects following Mohs micrographic surgery (MMS), the aesthetic unit principles should be applied. Often multiple staged procedures and revisions are necessary.

Objective: To analyze the reconstructive options and outcomes for complex facial defects per aesthetic unit.

Methods: Data of 202 patients, who underwent a facial reconstruction at the department of plastic and reconstructive surgery following MMS, were collected.

Results: The central facial units were affected in more than 70%, with over 20% of the defects involving more than 1 unit. Nasal defects required the longest reconstruction time (3-staged forehead flap) and periocular defects the most revisional procedures. In more than 50%, additional operations (range, 1-5) were needed. In 12%, postoperative complications occurred.

Conclusion: An overview for the reconstructive options of extensive facial skin cancer is presented. Proper treatment requires a structured multidisciplinary approach in order to achieve excellent tumour control and a satisfactory aesthetic and functional end result.
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http://dx.doi.org/10.1177/1203475415586665DOI Listing
December 2015

Subtyping basal cell carcinoma by clinical diagnosis versus punch biopsy.

Acta Derm Venereol 2015 Nov;95(8):996-8

Department of Dermatology, Maastricht University Medical Centre, P. Debyelaan 25, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands.

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http://dx.doi.org/10.2340/00015555-2113DOI Listing
November 2015

Topical photodynamic therapy using different porphyrin precursors leads to differences in vascular photosensitization and vascular damage in normal mouse skin.

Photochem Photobiol 2014 Jul-Aug;90(4):896-902. Epub 2014 Apr 7.

Department of Dermatology, Erasmus MC, Rotterdam, The Netherlands.

Different distributions of hexyl aminolevulinate (HAL), aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) in the superficial vasculature are not well studied but they are hypothesized to play an important role in topical photodynamic therapy (PDT). The colocalization of fluorescent CD31 and protoporphyrin IX (PpIX) was calculated using confocal microscopy of mouse skin sections to investigate the vascular distribution after topical application. Vascular damage leads to disruption of the normal endothelial adherens junction complex, of which CD144 is an integral component. Therefore, normal CD31 combined with loss of normal fluorescent CD144 staining was visually scored to assess vascular damage. Both the vascular PpIX concentration and the vascular damage were highest for HAL, then ALA and then MAL. Vascular damage in MAL was not different from normal contralateral control skin. This pattern is consistent with literature data on vasoconstriction after PDT, and with the hypothesis that the vasculature plays a role in light fractionation that increases efficacy for HAL and ALA-PDT but not for MAL. These findings indicate that endothelial cells of superficial blood vessels synthesize biologically relevant PpIX concentrations, leading to vascular damage. Such vascular effects are expected to influence the oxygenation of tissue after PDT which can be important for treatment efficacy.
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http://dx.doi.org/10.1111/php.12271DOI Listing
September 2015

Photodynamic and Nail Penetration Enhancing Effects of Novel Multifunctional Photosensitizers Designed for The Treatment of Onychomycosis.

Photochem Photobiol 2014 01 25;90(1):189-200. Epub 2013 Nov 25.

Department of Radiaotherapy, Center for Optical Diagnostics and Therapy, Erasmus Medical Centre, Rotterdam, The Netherlands.

Novel multifunctional photosensitizers (MFPSs), 5,10,15-tris(4-N-methylpyridinium)-20-(4-phenylthio)-[21H,23H]-porphine trichloride (PORTH) and 5,10,15-tris(4-N-methylpyridinium)-20-(4-(butyramido-methylcysteinyl)-hydroxyphenyl)-[21H,23H]-porphine trichloride (PORTHE), derived from 5,10,15-Tris(4-methylpyridinium)-20-phenyl-[21H,23H]-porphine trichloride (Sylsens B) and designed for treatment of onychomycosis were characterized and their functionality evaluated. MFPSs should function as nail penetration enhancer and as photosensitizer for photodynamic treatment (PDT) of onychomycosis. Spectrophotometry was used to characterize MFPSs with and without 532 nm continuous-wave 5 mW cm(-2) laser light (± argon/mannitol/NaN3 ). Nail penetration enhancement was screened (pH 5, pH 8) using water uptake in nails and fluorescence microscopy. PDT efficacy was tested (pH 5, ± argon/mannitol/NaN3 ) in vitro with Trichophyton mentagrophytus microconida (532 nm, 5 mW cm(-2) ). A light-dependent absorbance decrease and fluorescence increase were found, PORTH being less photostable. Argon and mannitol increased PORTH and PORTHE photostability; NaN3 had no effect. PDT (0.6 J cm(-2) , 2 μm) showed 4.6 log kill for PORTH, 4.4 for Sylsens B and 3.2 for PORTHE (4.1 for 10 μm). Argon increased PORTHE, but decreased PORTH PDT efficacy; NaN3 increased PDT effect of both MFPSs whereas mannitol increased PDT effect of PORTHE only. Similar penetration enhancement effects were observed for PORTH (pH 5 and 8) and PORTHE (pH 8). PORTHE is more photostable, effective under low oxygen conditions and thus realistic candidate for onychomycosis PDT.
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http://dx.doi.org/10.1111/php.12196DOI Listing
January 2014

[Skin cancer: from smearing to cutting].

Ned Tijdschr Geneeskd 2013 ;157(12):A5602

MUMC; afd. Dermatologie, Maastricht, the Netherlands.

The most common skin cancers are basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Conventional excision is still the current treatment of choice for these malignant tumours. Given the many subtypes and high incidence, the treatment of these skin tumours is not only a matter of surgical procedures. There are many different therapeutic options, from smearing to cutting. Those treating patients with non-melanoma skin cancer should have knowledge of the advantages and disadvantages of these many options. Radical surgical treatment is desired, but large margins are preferably avoided. Mohs micrographic surgery is a treatment option available for BCC and SCC in the face. Superficial BCC can be effectively treated with optimal cosmetic outcome in various, non-invasive ways.
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May 2013

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.

Acta Derm Venereol 2012 Nov;92(6):641-7

Department of Dermatology, Erasmus MC, PO box 2040, 3000 CA Rotterdam, The Netherlands.

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.
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http://dx.doi.org/10.2340/00015555-1448DOI Listing
November 2012

[Basal cell carcinoma: often more than one].

Ned Tijdschr Geneeskd 2011 ;155(47):A4110

Erasmus MC Universitair Medisch Centrum, Rotterdam, Afd. Dermatologie, the Netherlands.

Objective: To calculate the cumulative risks and incidence rates for the development of multiple (two or more) basal cell carcinomas (BCC).

Design: A retrospective cohort study with data from PALGA, the nationwide network and registry of histopathology and cytopathology in the Netherlands.

Method: Using pathology reports, the first 2483 patients diagnosed with a first histologically confirmed BCC in the year 2004 were retrospectively followed for 5 years. The Andersen-Gill survival analysis was used to study whether gender or age affected the risk of developing multiple BCCs.

Results: In total, 2483 patients developed 3793 BCCs. The five-year cumulative risk of developing multiple BCCs was 29.2%. The incidence rate for the development of two or more BCCs was 25,318 per 100,000 person-years in the first half year after first BCC diagnosis, decreasing to 6953 per 100,000 person-years after 5 years of follow-up. Compared with women men had a 30% (adjusted HR 1.30; 95% CI 1.11-1.53) higher risk of developing multiple BCCs and those aged 65-79 years had an 80% (adjusted HR 1.81; 95% CI 1.37-2.41) higher risk of having two or more BCCs compared with patients younger than 50 years.

Conclusion: Almost one third of the patients with a BCC developed two or more BCCs, most frequently in the period shortly after the first BCC. At diagnosis of BCC a full body skin examination should be performed and repeated annually for at least three years.
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February 2018

Monitoring blood volume and saturation using superficial fibre optic reflectance spectroscopy during PDT of actinic keratosis.

J Biophotonics 2011 Oct 15;4(10):721-30. Epub 2011 Aug 15.

Department of Dermatology, Erasmus MC, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands.

Optically monitoring the vascular physiology during photodynamic therapy (PDT) may help understand patient-specific treatment outcome. However, diffuse optical techniques have failed to observe changes herein, probably by optically sampling too deep. Therefore, we investigated using differential path-length spectroscopy (DPS) to obtain superficial measurements of vascular physiology in actinic keratosis (AK) skin. The AK-specific DPS interrogation depth was chosen up to 400 microns in depth, based on the thickness of AK histology samples. During light fractionated aminolevulinic acid-PDT, reflectance spectra were analyzed to yield quantitative estimates of blood volume and saturation. Blood volume showed significant lesion-specific changes during PDT without a general trend for all lesions and saturation remained high during PDT. This study shows that DPS allows optically monitoring the superficial blood volume and saturation during skin PDT. The patient-specific variability supports the need for dosimetric measurements. In DPS, the lesion-specific optimal interrogation depth can be varied based on lesion thickness.
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http://dx.doi.org/10.1002/jbio.201100053DOI Listing
October 2011

Fractionated illumination at low fluence rate photodynamic therapy in mice.

Photochem Photobiol 2010 Sep-Oct;86(5):1140-6

Department of Dermatology, Erasmus MC, Rotterdam, The Netherlands.

Photodynamic therapy (PDT) for actinic field cancerization is effective but painful. Pain mechanisms remain unclear but fluence rate has been shown to be a critical factor. Lower fluence rates also utilize available oxygen more efficiently. We investigated PDT effect in normal SKH1-HR mice using low and high fluence rate aminolevulinic acid (ALA) PDT and a fractionated illumination scheme. Six groups of six mice with different light treatment parameters were studied. Visual skin damage was assessed up to 7days post-PDT. Fluorescence and reflectance spectroscopy during illuminations provided us with real-time information about protoporphyrin IX (PpIX) photobleaching. A novel dosing approach was introduced in that we used a photobleaching percentage instead of a preset fluence. Data show similar total and maximum damage scores in high and low fluence rate groups. Photobleaching of PpIX in the low fluence rate groups shows a trend toward more efficient photobleaching. Results indicate that low fluence rate PDT is as effective as and more efficient than high fluence rate PDT in normal mouse skin. Low fluence rate PDT light protocols need to be explored in human studies in search for an effective and well-tolerated treatment for actinic field cancerization.
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http://dx.doi.org/10.1111/j.1751-1097.2010.00760.xDOI Listing
March 2011

Population education in preventing skin cancer: from childhood to adulthood.

J Drugs Dermatol 2010 Feb;9(2):112-6

Department of Dermatology and bDepartment of Public Health, Erasmus MC University Medical Center, Rotterdam, The Netherlands.

Skin cancer is the most commonly diagnosed cancer in populations of predominantly Caucasian origins. As the main cause of skin cancer is excessive sun exposure among a sun-sensitive population, most skin cancers are theoretically avoidable, and prevention is an important topic for public health purposes. The development of skin cancer may be limited by effective primary prevention campaigns, causing people to protect themselves from the sun. In order to be effective, the right people need to become aware of the risks and benefits; they also need to be convinced that they can take effective protective measures. Secondary skin cancer prevention aims to avoid skin cancer morbidity and mortality and is, therefore, mainly aimed at early detection of cutaneous melanomas. Around the world, elderly men are the worst off in terms of melanoma mortality statistics and would be an important target group for secondary prevention. Several prevention initiatives have been developed, including awareness campaigns and voluntary skin cancer screening days. So far, few of these initiatives have proven to be successful in changing population behavior and/or skin cancer related mortality. Most of these initiatives appealed more to (young) women rather than the elderly males who would benefit most. In this review, various aspects of primary and secondary skin cancer prevention are discussed, including the results of some of the primary and secondary prevention initiatives.
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February 2010

Microscopic distribution of protoporphyrin (PpIX) fluorescence in superficial basal cell carcinoma during light-fractionated aminolaevulinic acid photodynamic therapy.

Acta Derm Venereol 2008 ;88(6):547-54

Department of Dermatology, Erasmus MC Rotterdam, The Netherlands.

Light fractionation in aminolaevulinic acid photodynamic therapy (PDT) of superficial basal cell carcinoma has been shown to enhance the therapeutic efficacy significantly. We have shown previously that this increase in efficacy is not simply due to an increase in the amount of protoporphyrin utilized during therapy. The present study investigated the spatial distribution of protoporphyrin in 32 superficial basal cell carcinomas undergoing light-fractionated PDT. Superficial fluorescence imaging performed during therapy was compared with the microscopic analysis of protoporphyrin fluorescence in biopsies acquired immediately before the second of two light fractions. The microscopic distribution of fluorescence was also compared with tumour sections immunohistochemically stained for Ki-67. Large variations in superficial and microscopic protoporphyrin fluorescence were found in both control and treated lesions. Despite these variations there was a reasonable correlation between the two techniques (R2=0.86). The mean fluorescence intensity in control biopsies was greater than in illuminated lesions before the second light fraction, but there was no significant difference in the variation within and between regions of interest in each of these sets of lesions. There was no clear trend in depth of protoporphyrin reappearance during the dark interval between light fractions. The general distribution of cells stained positive for Ki-67 followed the protoporphyrin fluorescence that was associated with islands of basal cell carcinoma. In conclusion, this study confirms that the mean relative re-synthesis of protoporphyrin after PDT is consistent with that found previously in pre-clinical models. There are large variations in fluorescence within superficial basal cell carcinoma that include regions of tumour cells that do not synthesize protoporphyrin.
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http://dx.doi.org/10.2340/00015555-0508DOI Listing
January 2009

Light fractionation does not enhance the efficacy of methyl 5-aminolevulinate mediated photodynamic therapy in normal mouse skin.

Photochem Photobiol Sci 2007 Dec 28;6(12):1325-31. Epub 2007 Aug 28.

Center for Optical Diagnostics and Therapy, Department of Radiation Oncology, Erasmus MC, Room Wk-319, PO box 2040, 3000, CA, Rotterdam, The Netherlands.

Previous work demonstrated that fractionated illumination using two fractions separated by a dark interval of 2 h, significantly enhanced the clinical efficacy of photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA). Considering the increasing clinical use of methyl 5-aminolevulinate (MAL) and the expected gain in efficacy by light fractionation we have investigated the response to MAL-PDT using a single and a two-fold illumination scheme and compared that with ALA-PDT. Our results show that fractionated illumination does not enhance the efficacy of PDT using MAL as it does using ALA despite the comparable fluorescence intensities at the end of the first light fraction and at the start of the second light fraction. Only the initial rate of photobleaching was slightly greater during ALA-PDT although the difference was small. Previously we hypothesized that cells surviving the first fraction are more susceptible to the second fraction. Since this is not true for MAL-PDT our data suggest that the distribution of MAL and ALA in tissues, and therefore the site of PDT induced damage, is an important parameter in the mechanism underlying the 2-fold illumination scheme.
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http://dx.doi.org/10.1039/b708340hDOI Listing
December 2007

Question the obvious.

Arch Dermatol 2007 Nov;143(11):1429-32

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http://dx.doi.org/10.1001/archderm.143.11.1429DOI Listing
November 2007

Topical 5-aminolevulinic acid mediated photodynamic therapy of superficial basal cell carcinoma using two light fractions with a two-hour interval: long-term follow-up.

Acta Derm Venereol 2006 ;86(5):412-7

Photodynamic Therapy and Optical Spectroscopy Program, Department of Radiation Oncology, Daniel den Hoed Oncology Centre, Rotterdam, The Netherlands.

Photodynamic therapy (PDT) of superficial basal cell carcinoma using topical 5-aminolaevulinic acid (ALA) and 75-100 J/cm2 light dose yields unsatisfactory long-term results. In several animal models, illumination with two light fractions approximately 2 h apart was considerably more effective than single illumination, suggesting the need for a pilot clinical study. Fifteen patients with a total of 86 primary superficial basal cell carcinomas, received topical ALA and were illuminated 4 and 6 h later, both with 45 J/cm2 laser light (633+/-1 nm). Fluorescence spectra were measured before and immediately after each illumination. At a mean follow-up of 59 months (range 44-82), 67 lesions could be evaluated, 56 of which showed a complete response (84%). Cosmesis was good/excellent in 88% of the complete response group and fair in 12%. There was no correlation between protoporphyrin fluorescence and response, but a significant correlation between the percentage of fluorescence left after photobleaching by the first illumination and the amount of protoporphyrin re-synthesized 2 h later. In conclusion, the long-term complete remission rate of fractionated ALA-mediated PDT of superficial basal cell carcinoma as reported here is significantly better than after PDT with single illumination previously reported by others, but equal to studies using single illumination with a much higher light fluence. Further improvement may be possible by reducing the fluence of the first fraction, with constant total fluence.
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http://dx.doi.org/10.2340/00015555-0129DOI Listing
November 2006

Fractionated illumination significantly improves the response of superficial basal cell carcinoma to aminolevulinic acid photodynamic therapy.

J Invest Dermatol 2006 Dec 13;126(12):2679-86. Epub 2006 Jul 13.

Department of Dermatology, Erasmus MC, Rotterdam, The Netherlands.

Photodynamic therapy (PDT) of superficial basal cell carcinoma (sBCC) using topical 5-aminolevulinic acid (ALA) and a light fluence of 75-100 J cm(-2) yields unsatisfactory long-term results. In several animal models, illumination with two light fractions 2 hours apart was considerably more effective than single illumination. Response is further enhanced if the fluence of the first light fraction is reduced, although the cumulative fluence is maintained. We compared the response of sBCC to a single illumination and 2-fold illumination scheme in which two light fractions of 20 and 80 J cm(-2) are performed 4 and 6 hours after the application of a single dose of 20% ALA. We randomly assigned 154 patients with a total of 505 primary sBCC into two treatment groups. Two hundred and forty-three lesions were treated using a single illumination of 75 J cm(-2) at a fluence rate of 50 mW cm(-2). Fractionated PDT, at the same fluence rate, was performed on 262 lesions. The complete response (CR) following a 2-fold illumination scheme is significantly greater than that following a single light fraction (P=0.002, log-rank test). Twelve months after therapy, CR rate to a 2-fold illumination is 97%, whereas the CR to a single illumination is 89%.
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http://dx.doi.org/10.1038/sj.jid.5700460DOI Listing
December 2006

The glucagonoma syndrome and necrolytic migratory erythema: a clinical review.

Eur J Endocrinol 2004 Nov;151(5):531-7

University Medical Center Groningen, Department of Endocrinology, PO Box 30.001, 9700 RB Groningen, The Netherlands.

The glucagonoma syndrome is a rare disease in which a typical skin disorder, necrolytic migratory erythema, is often one of the first presenting symptoms. Weight loss and diabetes mellitus are two other prevalent characteristics of this syndrome. Necrolytic migratory erythema belongs to the recently recognized family of deficiency dermatoses of which zinc deficiency, necrolytic acral erythema and pellagra are also members. It is typically characterized on skin biopsies by necrolysis of the upper epidermis with vacuolated keratinocytes. In persistent hyperglucagonemia, excessive stimulation of basic metabolic pathways results in diabetes mellitus at the expense of tissue glycogen stores, and muscle and fat mass. Multiple (essential) nutrient and vitamin B deficiencies develop, which contribute to the dermatosis. In addition, glucagonomas may produce various other products, like pancreatic polypeptide, that add to the catabolic effects of glucagon.
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http://dx.doi.org/10.1530/eje.0.1510531DOI Listing
November 2004
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