E.R.M. de Haas

Cumulative risks and rates of subsequent basal cell carcinomas in the Netherlands.

Backgroundu2002 The incidence of multiple basal cell carcinomas (BCCs) is not well documented.

Topical hexylaminolevulinate and aminolevulinic acid photodynamic therapy: Complete arteriole vasoconstriction occurs frequently and depends on protoporphyrin IX concentration in vessel wall

Vascular responses to photodynamic therapy (PDT) may influence the availability of oxygen during PDT and the extent of tumor destruction after PDT. However, for topical PDT vascular effects are largely unknown. Arteriole and venule diameters were measured before and after hexylaminolevulinate (HAL) and aminolevulinic acid (ALA) PDT and related to the protoporphyrin IX (PpIX) concentration in the vessel wall. A mouse skin fold chamber model and an intravital confocal microscope allowed direct imaging of the subcutaneous vessels underlying the treated area. In both HAL and ALA groups over 60% of arterioles constricted completely, while venules generally did not respond, except for two larger veins that constricted partially. Arteriole vasoconstriction strongly correlated with PpIX fluorescence intensity in the arteriole wall. Total PpIX fluorescence intensity was significantly higher for HAL than ALA for the whole area that was imaged but not for the arteriole walls. In conclusion, complete arteriole vasoconstriction occurs frequently in both HAL and ALA based topical PDT, especially when relatively high PpIX concentrations in arteriole walls are reached. Vasoconstriction will likely influence PDT effect and should be considered in studies on topical HAL and ALA-PDT. Also, our results may redefine the vasculature as a potential secondary target for topical PDT.

Recommendations for treatment in folliculotropic mycosis fungoides : report of the Dutch Cutaneous Lymphoma Group

Folliculotropic mycosis fungoides (FMF) is an aggressive variant of mycosis fungoides (MF) and generally less responsive to standard skin‐directed therapies (SDTs). Recent studies distinguished indolent (early‐stage FMF) and more aggressive (advanced‐stage FMF) subgroups. The optimal treatment for both subgroups remains to be defined.

Detection and differentiation of causative organisms of onychomycosis in an ex vivo nail model by means of Raman spectroscopy

Onychomycosis is worldwide the most prevalent infection of the nail. It is mainly caused by the dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes and to a lesser extent Trichophyton tonsurans. The yeast Candida albicans and the mould Scopulariopsis brevicaulis can also cause onychomycosis. Management of these nail conditions may require appropriate treatment methods and therefore the identification of the causative species can be of importance. However, the determination of agents causing onychomycosis is still not optimal.

Non-HIV-related Kaposi's sarcoma suppressed by dapsone

Summary Two patients with a history of slowly progressive non‐HIV‐related Kaposis sarcoma were successfully treated with dapsone.

Treatment of superficial basal cell carcinoma by topical photodynamic therapy with fractionated 5-aminolaevulinic acid 20% vs. two-stage topical methyl aminolaevulinate: results of a randomized controlled trial

Basal cell carcinoma (BCC) is the most common type of skin cancer and incidence rates are increasing. Photodynamic therapy (PDT) is a frequently used treatment, especially for superficial BCC (sBCC). Two topical photosensitizing agents are currently used to treat sBCC, namely 5‐aminolaevulinic acid (ALA) and its ester, methyl aminolaevulinate (MAL). Previous research showed a high efficacy for ALA‐PDT using a twofold fractionated illumination scheme in which two light fractions of 20 J cm−2 and 80 J cm−2 were delivered 4 h and 6 h after ALA application.

Light Fractionated ALA-PDT: From Pre-Clinical Models to Clinical Practice

Photodynamic therapy of superficial basal cell carcinoma using topical 5-aminolevulinic acid and a light fluence of 75-100 J cm−2 yields unsatisfactory long term clinical response rates. In a range of pre-clinical models illumination with two light fractions separated by 2 hours apart was considerably more effective than single illumination. Response is further enhanced if the fluence of the first light fraction is reduced while the cumulative fluence is maintained. We have demonstrated that these encouraging pre-clinical results are also evident for the clinical ALA-PDT of the treatment of superficial basal cell carcinoma. In a large scale randomised study including 505 primary sBCC we have shown that therapy using two light fractions of 20 and 80 Jcm−2 performed 4 and 6 hours after the application of a single dose of 20% ALA results in a significant increase in complete response (P 0.002, log-rank test). Twelve months after therapy, complete response rate following a two-fold illumination is 97% whereas the complete response to a single illumination is 89%. Numerous studies are underway investigating the mechanism underlying the increase in tissue response. Increased efficacy is not simply associated with an increasing PpIX content of the tissues during the treatment scheme and there is no direct relationship between the total amount of PpIX utilised and efficacy. We have shown that fractionated illumination does not enhance the efficacy of PDT using methyl-ester derivatives of ALA despite almost identical PpIX fluorescence kinetics during therapy. Our most recent data suggest that the in-vivo distribution of MAL and ALA and the exact site of PDT induced damage, is an important parameter in the mechanism underlying fractionated illumination for ALA-PDT. There is significant potential for the future use of light fractionation in other organs.

Evaluation of treatment results in multifocal primary cutaneous anaplastic large cell lymphoma: Report of the Dutch Cutaneous Lymphoma Group

There is no consensus on the treatment of multifocal primary cutaneous anaplastic large cell lymphoma (C‐ALCL). Radiotherapy (RT) and methotrexate (MTX) are the current treatment options, but their efficacy is unknown. Recently, targeted therapies showed promising results in C‐ALCL, and may therefore be an attractive first choice of treatment.

使用分级5-氨基酮戊酸20%和二级局部氨基乙酰丙酸甲酯通过局部光动力疗法来治疗表浅性基底细胞癌:随机对照试验结果

光动力疗法(PDT)常用于治疗表浅性基底细胞癌(sBCC)。它通过将卟啉前体膏涂抹于所影响的皮肤部位,并盖上敷料来治疗。几小时后揭开闭合的敷料,使用高强度的可见光照射皮肤部位,使癌细胞死亡。荷兰有两种卟啉前体,分别为5‐氨基酮戊酸20% (ALA)和氨基乙酰丙酸甲酯(MAL)。在传统MAL PDT中,皮肤每隔一周照射一次(光治疗)。对于ALA,皮肤每隔两小时接受两次不同的照射。这被称为分级ALA‐PDT。在这项来自荷兰的研究中,我们调查了这种分级ALA‐PDT是否优于传统MAL‐PDT。162名患者被随机分成两组。82名患者使用分级ALA‐PDT治疗,80名患者使用传统MAL‐PDT。12个月后,ALA‐PDT组有6起治疗失败(sBCC复发),MAL‐PDT组有13起治疗失败。尽管MAL‐PDT组的治疗失败数量高出一倍,但这一差异不具有统计显著性。其次,我们调查了两个治疗组的疼痛分数,因为PDT据悉会引起严重的灼烧感。我们发现与MAL‐PDT相比,ALA‐PDT会导致更剧烈的疼痛和更多副作用,例如红斑(红疹,如晒斑)、伤口/糜烂和囊泡(小水泡)。因此,对于治疗sBCC,相比MAL‐PDT,ALA‐PDT趋向于有更好的疗效,尽管差异并不显著。

Light fractionation increases the efficacy of ALA-PDT but not of MAL-PDT: What is the role of (vascular) endothelial cells?

Photodynamic therapy (PDT) using protoporpyrin IX (PpIX) precursors like 5-aminolevulinic acid (ALA) or methyl-aminolevulinate (MAL) has shown to be effective in the treatment of various skin diseases. Using ALA we have shown in numerous studies a significantly improved efficacy by applying light fractionation with a long dark interval. In contrast, in the hairless mouse model, the PDT efficacy using MAL is unaffected by adopting this approach. More acute edema is found after ALA-PDT suggesting a difference in response of endothelial cells to PDT. To investigate the role of endothelial cells, cryo-sections of hairless mouse skin after 4 hours of topical MAL or ALA application were stained with a fluorescent endothelial cell marker (CD31). Co-localization of this marker with the PpIX fluorescence was performed using the spectral imaging function of the confocal microscope. We have also used intra-vital confocal microscopy to image the PpIX fluorescence distribution in correlation with the vasculature of live mouse skin. Our results show PpIX fluorescence at depth in cryo-sections of mouse skin after 4 hours of topical application. Co-localization has shown to be difficult due to the changes in tissue organization caused by the staining procedure. As expected we found high PpIX fluorescence levels in the epidermis after both MAL and ALA application using intra-vital microscopy. After ALA application more PpIX fluorescence was found deep in the dermal layer of the skin than after MAL. Furthermore we detected localized fluorescence in unidentified structures that could not be correlated to blood vessels or nerves.