Topical ALA-PDT as alternative therapeutic option in treatment-recalcitrant dermatosis: Report of 4 cases

BackgroundTopical Photodynamic therapy (PDT) is widely acknowledged for its safety and effectiveness in treating oncologic skin diseases such as basal cell carcinoma, actinic keratosis and squamous cell carcinoma in situ. Despite its broad applications in dermatology, this method is a relatively new therapeutic option for treating inflammatory/infectious skin diseases.ObjectivesTo determine whether topical PDT is a safe and effective treatment option in treating treatment-recalcitrant dermatosis.ObservationsWe presented one of each case of Acne Vulgaris, facial flat warts, urethral meatus Condyloma Acuminatum and extramammary Paget’s disease, where other treatment options were either ineffective or not feasible, then those patients underwent topical PDT and showed significant improvement with minimal side effects.ConclusionsTopical PDT therapy may be applied in cases of Acne Vulgaris, facial flat warts, urethral meatus Condyloma Acuminatum and extramammary Paget’s disease, where other treatment has shown no or minimal improvement, or in whom ablative or invasive procedure is to be avoided or not well tolerated.     

Bringing the gentle properties of daylight photodynamic therapy indoors: A systematic review of efficacy and safety

Classic photodynamic therapy (PDT) is an effective, but painful, treatment of actinic keratosis (AK). Daylight PDT with simultaneous activation of protoporphyrin IX during its formation is almost painless and as effective. Recent studies suggest that this gentle simultaneous activation can be performed indoors by replacing daylight with a suitable light source. We aimed to systematically review efficacy and tolerability of indoor gentle PDT of AKs using various light sources. We systematically searched MEDLINE, Embase, and the Cochrane Library for clinical studies of treatment efficacy or adverse events. Indoor gentle PDT consists of application of methyl aminolevulinate or 5-aminolevulinic acid on the skin prior to long time illumination, starting no later than one hour after application. Fifteen studies met the selection criteria, enrolling 518 patients with more than 5,000 AKs undergoing indoor gentle PDT. The studies mainly included thin AKs comprised of 8 uncontrolled studies and 7 randomized controlled trials (RCT) of which 3 were designed as non-inferiority RCTs. Results from both controlled and uncontrolled trials indicated good treatment tolerability with very low pain scores like those of daylight PDT. Reduction of AK lesions 3 months after indoor gentle PDT in RCTs ranged from 52% to 79%, which is comparable to classic and daylight PDT. All 3 non-inferiority RCTs reported that indoor gentle PDT was non-inferior in terms of efficacy to classic PDT. The included studies used varying treatment protocols with different pretreatments, incubation time, light sources, and irradiation time. No standard protocol for indoor gentle PDT exists yet.     

Inflammation burst after 5-aminolevulinic acid-photodynamic therapy for the treatment of actinic keratosis complicating rosacea: A case report

A 72-year-old woman suffering from multiple actinic keratosis (AK) complicating steroid-induced rosacea received 5-aminolevulinic acid-photodynamic therapy (ALA-PDT) in our outpatient clinic. Both AKs and rosacea achieved remission after one session of PDT. However, an adverse effect of severe acute inflammatory response emerged with lasting hyperpigmentation. We then terminated the following PDT sessions . After skin care and close follow-up for a half year, most symptoms and lesions of AK and rosacea disappeared with mild hyperpigmentation left. ALA-PDT is commonly recommended for multiple AKs based on effectiveness and noninvasiveness, but has controversial efficacy and safety for rosacea. The unusual excessive inflammation in this patient after ALA-PDT may due to skin barrier destruction, vasomotor dysfunction and the immune response by dead Demodex after PDT. This case indicated that carefully evaluation before ALA-PDT is of great importance, especially for those patients with complicated skin situation. For AKs complicating rosacea, modified parameters of ALA-PDT such as less ALA incubation time or reduced light dose should be further studied to achieve the optimal efficacy and safety of ALA-PDT and offer the best benefit.     

Photodynamic therapy and pain: A systematic review

Photodynamic therapy (PDT) is an effective treatment for actinic keratoses and early skin cancers, and the only office procedure to control field cancerization. Procedure-associated pain limits widespread PDT use and by early termination of treatment can decrease overall therapeutic efficacy. Here we review and assess reported interventions on PDT-associated pain, in order to identify the most promising methods to manage treatment-associated pain and identify focus for future studies. Literature search was performed using MEDLINE, EMBASE, and the Cochrane Library by two independent reviewers to select publications that assessed and compared pain quantitatively during PDT treatment for actinic keratoses, basal cell carcinomas, and/or in situ squamous cell carcinomas. A total of 48 studies reporting on pain during PDT were identified and were comprised of two main categories of interventions: pain-controlling therapies and PDT parameter (photosensitizer or photo-irradiation) adjustments. Of these interventions: nerve block, subcutaneous infiltration anesthesia, cold analgesia, and transcutaneous electrical nerve stimulation, but not topical anesthetic gels, were associated with less PDT-related pain; 5-aminolevulinic acid (ALA) tended to be more painful than methyl-5-aminolevulinate (MAL); daylight PDT was less painful than conventional PDT; and lower irradiance delivery produced lower pain scores in general. There is no single crystalized protocol for management of PDT-related pain. Evidence suggests that continuous activation of low levels of PpIX with methods using lower irradiance and possibly shorter incubation times are associated with decreased pain without loss of PDT efficacy. Protocols to reduce pain should be standardized and large controlled trials are needed.     

Photodynamic therapy in dermatology beyond non-melanoma cancer: An update

Photodynamic therapy (PDT) employs a photosensitizer (PS) and visible light in the presence of oxygen, leading to production of cytotoxic reactive oxygen species, which can damage the cellular organelles and cause cell death. In dermatology, PDT has usually taken the form of topical application of a precursor in the heme biosynthesis pathway, called 5-aminolevulinic acid (or its methyl ester), so that an active PS, protoporphyrin IX accumulates in the skin. As PDT enhances dermal remodeling and resolves chronic inflamation, it has been used to treat cutaneous disorders include actinic keratoses, acne, viral warts, skin rejuvenation, psoriasis, localized scleroderma, some non-melanoma skin cancers and port-wine stains. Efforts are still needed to mitigate the side effects (principally pain) and improve the overall procedure.     

Randomized controlled trial for evaluation of efficacy and pain during photodynamic therapy for actinic keratosis of face and scalp comparing two irradiation protocols

BackgroundPain is a frequent adverse event during photodynamic therapy, which can limit treatment acceptance. This study aimed to evaluate the efficacy and pain during photodynamic therapy with two irradiation protocols in patients with actinic keratosis on the face and scalp.MethodsIn this intra-patient randomized controlled trial, participants were randomly allocated to receive photodynamic therapy with methyl aminolevulinate and red light on the right or left side with protocol 1 (irradiation device in contact with the skin) and protocol 2 (device 3 cm away from the skin). There was a 15-day interval between the protocols. The primary outcome was the frequency of mean intensity of moderate or severe pain during photodynamic therapy. Secondary outcomes were actinic keratosis clearance rate, protoporphyrin IX consumption, participant preference, skin appearance, and adverse events.ResultsForty-one participants were included, yielding 47 and 50 randomized sites for protocols 1 and 2. There was no difference in the frequency of moderate and severe pain, with a relative risk of 1.09 (95% CI 0.70–1.70), p>0.05. An actinic keratosis count reduction >60% was observed in both protocols (p<0.01), with no difference between them. There was no difference in protoporphyrin IX consumption. Most treated sites were of good to excellent quality. There was a greater patient preference for protocol 2 (p<0.01).ConclusionsThe pain intensity was similar between the protocols, and the protocols were equally effective for actinic keratosis clearance, protoporphyrin IX consumption, and improvement in the quality of the treated areas. Both protocols may be considered safe.     

Current status of PDT in the United States

The field of photodynamic therapy (PDT) continues to make significant progress in the United States of America (USA). There are currently about 23 recruiting interventional clinical studies designed to evaluate the safety and efficacy of PDT in adult patients, in the USA [1]. Skin cancer and lung cancer are the primary sites with four studies investigating PDT for the treatment of basal cell carcinoma (BCC), one study using PDT to treat non-melanoma skin cancer in patients with solid organs transplant, three evaluating PDT in the treatment of actinic keratosis, and another study aims to treat acne. Three studies evaluating PDT in the treatment of non-small cell lung cancer with pleural disease, two of these studies include malignant mesothelioma, and one targeting locally advanced and metastasis that induce airway obstruction. In other disease sites there is one study that evaluates PDT in the treatment of head and neck cancer, non-muscle invasive bladder cancer, pancreatic cancer, esophageal cancer, anal cancer, prostate cancer or low-grade upper tract urothelial cancer. One study evaluates PDT in the treatment neurofibromatosis type 1, and one study evaluates the safety and feasibility of PDT to sterilize deep tissue abscess cavities.Several photosensitizers are being used with investigational new drug approval or exemption by the USA food and drug administration (FDA) [1]. The FDA-approved porfimer sodium is being used to treat locally advanced lung cancer or lung cancer with pleural disease, malignant central airway obstruction, malignant mesothelioma, and head and neck cancer. The topical pro-drug, aminolevulinic acid (ALA) is being used to treat BCC and anal cancer, while one study adds 4% imipramine cream to ALA PDT to treat microvesicle particle in the skin. A vascular drug, padeliporfin dipotassium, is being evaluated in the treatment of early-stage prostate cancer and low-grade upper tract urothelial cancer. A ruthenium polypyridyl complex administered by instillation is being evaluated for efficacy in treating non-muscle invasive bladder cancer. Verteporfin is being evaluated for efficacy in the treatment of pancreatic cancer. The safety and feasibility of PDT with methylene blue is being evaluated for sterilizing deeply seated abscess cavities.Treatment planning and dosimetry are being employed by measuring light dose rate (irradiance) and dose (fluence), as well as singlet oxygen. There is no system that is currently approved for clinical use in the USA. The National Institutes of Health supports about 40 investigators-initiated projects in the USA [2]. Most of these projects focus on developing novel methods to improve the response to PDT. These include advanced treatment planning and dosimetry systems, imaging using photoacoustic or theranostic approaches, combination therapies that utilize PDT to enhance the response to chemotherapy, use of Vitamin D to improve treatment outcomes and employing molecular targeted probes and functional nanoparticles and liposomes.Acknowledgement: Thanks to Dr. Sherri McFarland for her constructive suggestions and comments.Conflict of interest: Dr. Shafirstein is a co-inventor of the optical surface applicator and dosimetry system (USPTO 11,344,742, 11,040,217). He acknowledges current service on a scientific advisory board with honoraria and stock options from Lumeda Inc.; receiving grant support from Lumeda Inc.; receiving in-kind contributions from Pinnacle Biologics Inc., and grant support from Johnson and Johnson Enterprise Innovation, Inc.     

Clinical evaluation of a short illumination duration (1 hour) when performing photodynamic therapy of actinic keratosis using the Dermaris light source

Photodynamic therapy (PDT) using daylight as the photoactivating light source (DL-PDT) is an effective treatment for actinic keratosis (AK). Among the artificial daylight sources, the Dermaris (Surgiris, Croix, France) is specially designed for SDL-PDT (simulated daylight PDT) of AK. To perform the PDT session, a long duration (2.5 h) and low-intensity light exposure (2.9 mw/cm²) is used. This long duration is considered as a major limitation by both the patient and the dermatologist. The study aims to evaluate the clinical outcomes of SDL-PDT using the Dermaris in patients treated for AK lesions of the scalp at our medical dermatology center using only one hour low-intensity light exposure.Thirty patients (19 males, 11 females), mean age: 72.8 ± 9.3, with phototype 1 (11 patients), with phototype 2(17 patients) and phototype 3 (2 patients), with grade I-II AK of the scalp were treated with a drug-light interval (DLI) of 10 min and a light exposure of 1 h. The cure rate of AK lesions at six months after the treatment was determined. Erythema, crusts, discomfort and during or/and post the treatment were also evaluated. In total, 293 AK were treated. Six months following treatment, the cure rate of patients was 93%. Pain score reported after the first PDT session was from 0 to 1 on a visual analogue scale (VAS) ranging from 0 to 10. Erythema was observed in 28 patients and lasted 3 days, crusts were seen in 19 patients. Discomfort was as mild or less in more than 97% of patients.The shortening of the exposure time to one hour does not modify the efficacy of the SDL-PDT using the Dermaris. This observation is in agreement with recent published data demonstrating that PDT can be performed successfully with half the illumination time used in daylight PDT today. Besides, this clinical study confirmed that SDL-PDT is an effective and nearly painless treatment with minimal side effects for patients with AK lesions of the scalp.     

Sandpaper curettage: A simple method to improve PDT outcomes for actinic keratosis

INTRODUCTIONPhotodynamic therapy (PDT) is a non-scarring, repeatable, and safe treatment for actinic keratosis (AK), but improvements in efficacy are still needed.BACKGROUNDDevices such as steel blades, needle rollers, and lasers are currently used to remove hypertrophic stratum corneum on AKs to improve PDT outcomes. However, curettage with fine sandpaper could be a gentler, effective alternative.METHODSA retrospective study was designed to compare PDT with or without sandpaper curettage. Patients were selected from a database registry of patients with face and scalp AKs (ClinicalTrials.gov NCT03319251). Patients in Group 1 underwent PDT alone (20% ALA, 15 min; blue light 417 nm, 30 min). Patients in Group 2 were pretreated with gentle sandpaper curettage prior to ALA and illumination. The two groups were compared using multivariate matching, normalizing for age, sex, initial AK counts, and time to follow-up.RESULTSSixty-six patients were selected for matching analysis (n=38, PDT only; n=28, PDT+curettage). Demographics between the groups were similar (mean ± SD), including age (71.0 ± 8.3 vs. 71.0 ± 8.0 years), baseline AK count (53 ± 39 vs. 44± 32), and time to post-PDT follow-up (111 ± 28 vs. 113 ± 32 days). At follow-up, patients who received curettage showed an overall 55% improvement in scalp AK clearance compared to patients who did not receive curettage, adjusting for sex, age, time to follow-up, and baseline AK count (p = 0.0322, multivariable linear regression).DISCUSSIONSandpaper curettage before PDT treatment is an easy and inexpensive method to significantly improve AK clearance rates.     

光动力学疗法在难治性良性皮肤病中的应用进展

光动力学疗法（photodynamie therapy，PDT）是通过局部或系统给予光敏剂后以特定波长激光照射从而对靶组织产生选择性的光敏化作用，其特殊的作用机制使其具有美容效果好、可重复应用而无耐药性等优点。最初PDT在皮肤科主要用于肿瘤的治疗，新近研究者尝试将PDT拓展到某些难治性良性皮肤病，如病毒疣、真菌感染、慢性炎症性疾病的治疗，并取得初步疗效，为上述皮肤病的治疗提供了新的思路。然而，目前还尚需大量的比较性研究以及PDT治疗方案的优化以确定PDT在上述疾病治疗中的地位。     

Photodynamic diagnosis (PDD) and photodynamic therapy (PDT) in dermatology: “How we do it”

In dermatology PDT has been proven to be effective in the treatment of actinic keratoses, basal cell carcinomas (BCC), Bowen's disease, superficial squamous cell carcinomas (SCC).     

Optical coherence tomography imaging of non-melanoma skin cancer undergoing photodynamic therapy reveals subclinical residual lesions

BackgroundPhotodynamic therapy with methyl aminolaevulinate (MAL–PDT) is a widely used non-invasive treatment modality for non-melanoma skin cancer (NMSC). The outcome of MAL–PDT is usually primarily evaluated clinically. Optical coherence tomography (OCT) is a non-invasive imaging technology based on interferiometry. OCT has been proven to provide high accuracy in identifying NMSC lesions and performing thickness measurements of thin tumours.ObjectivesTo describe the OCT morphology in in-vivo NMSC lesions during MAL–PDT treatment and to investigate the use of OCT in evaluating the response of MAL–PDT treated NMSC lesions.MethodsA total of 18 biopsy-proven basal cell carcinomas and actinic keratoses were monitored by OCT during 2 sessions of MAL–PDT treatment. At 3-months follow-up the patients were assessed both by OCT and clinically. If the clinical and OCT evaluation came to different conclusions on recurrence of the lesion, patients were followed more closely at clinical appointments for up to one year after the PDT treatment.ResultsAll lesions displayed at least one OCT characteristic before MAL–PDT treatment. At 3 months follow-up, recurrence was suspected clinically in 5/18 cases, with OCT in 7/18 cases. OCT correctly identified all of the partial responses also found by the clinical examinations. In both cases where recurrence was only found in OCT, this was subsequently confirmed by histology.ConclusionsOur study suggests that OCT identified 29% more recurrences than clinical examination alone. OCT can detect subclinical residual NMSC lesions after MAL–PDT treatment and may therefore be an accurate tool for early detection of residual lesional tissue.     

Artificial White Photodynamic Therapy: Advancing Actinic Keratosis Treatment

Natural DayLight-mediated PhotoDynamic Therapy (NDL-PDT) is an efficacious treatment option for thin actinic keratosis that offers advantages over conventional PDT in terms of tolerability and cost. It is now accepted that the minimum criteria required for effective NDL-PDT is a dose of 4 J/cm² with a treatment time of 2 hours and a minimum temperature of 10°C, corresponding to a minimum illuminance of 11,000 lux. This value is easily achievable: 20,000 lux can be obtained during a typical overcast day at midday. It can reach 110,000 lux with a bright sunlight. However, it is limited to certain times of the year at our latitude: rain and cold temperatures appear the main limitations of NDL-PDT. Greenhouses make possible to perform the illumination even in harsh weather conditions; but it is difficult to install a greenhouse everywhere.Several solutions are now proposed to carry out indoor illumination so-called artificial white light or simulated daylight (SDL-PDT). Illumination sources installed at the ceiling of the treatment room is one option. Several lamp pairs can be combined to illuminate groups of patients simultaneously. A surgical theatre light can be used or dedicated systems using white LEDs can be used to deliver the required illumination dose. In conclusion, Indoor lightning (or simulated daylight: SDL-PDT or Artificial White Light: AWL) could offer an interesting alternative to NDL-PDT for the treatment of Actinic Keratosis.     

Laser-photo-radiotherapy in the treatment malignant tumors

Photoradiation therapy or, as more recently defined, photodynamic therapy (PDT) has been effective in the treatment of several kinds of cancers, above all of the skin, lung, esophagus and bladder. It is based on the preferential retention by tumor and photosensitizing properties of certain porphyrins. We began to investigate this technique experimentally in 1978 and clinically in september 1982, with report of the initial results in 38 patients in 1985. In this paper we describe our more recent experience of PDT in 18 patients affected by different tumors and treated with a new double argon-dye laser system. These tumors included 8 carcinomas of the esophagus, 5 basal cell skin cancers, 2 carcinomas of the lung, 2 squamous cell carcinomas of the oral cavity and 1 early gastric cancer. Clinical results and technical problems of PDT are discussed.     

A quantitative study of in vivo protoporphyrin IX fluorescence build up during occlusive treatment phases

BackgroundTopical photodynamic therapy (PDT) is a non-invasive light based therapy used to treat non-melanoma skin cancer (NMSC) and dysplasia. During PDT, the light sensitive molecule protoporphyrin IX (PpIX) is activated, resulting in the production of singlet oxygen, which subsequently leads to cell death. PpIX is metabolised from a topically applied pro-drug and the strong fluorescence signal associated with PpIX can be utilised as an indicator of the amount of PpIX present within the tumour tissue. In this work we measure the build up PpIX during the occlusive treatment phase and investigate how the PpIX production rate is affected by different lesion and patient characteristics.MethodsFluorescence measurements were used to investigate the build up of PpIX within the tumour tissue during the 3 h long occlusive treatment prior to irradiation. The study included in vivo measurements of 38 lesions from 38 individual patients. Actinic keratosis (AK) and basal cell carcinoma (BCC) were the lesion types included in this study. The resulting data from the study was analysed using generalised linear mixed effects models.ResultsIt was found that the surface fluorescence signal linearly increased with occlusive treatment time. The predictive models suggest that there is a significant difference in PpIX production between lesion location, however no significant difference is demonstrated between different lesion types, gender and skin type.ConclusionsThe study extends and supports previous knowledge of PpIX production during the occlusive treatment phase.     

No room for pain: A prospective study showing effective and nearly pain-free treatment of actinic keratosis with simulated daylight photodynamic therapy (SDL-PDT) using the IndoorLux® System in combination with BF-200 ALA (Ameluz®)

BackgroundPhotodynamic therapy (PDT) with natural daylight is effective and less painful than conventional PDT when treating actinic keratosis (AK), however its weather dependency is restrictive. This prospective open-label observational single-arm study examined efficacy and safety of simulated daylight (SDL)-PDT using the IndoorLux® system in combination with 5-aminolevulinic acid gel (BF-200 ALA).Methods12 patients with mild/moderate AK on the face or scalp received two SDL-PDTs. BF-200 ALA was applied prior to a 2 h illumination with the IndoorLux® System. Patients evaluated pain during and after SDL-PDT on visual analogue scales (VAS). Primary endpoint was lesion count reduction three months after the second SDL-PDT. Secondary endpoint was pain during and after illumination.ResultsMedian individual clearance rate was 83.75% (66.7–100.0%); 33.3% of the patients and 84.9% of the lesions were completely cleared. Median size of the remaining partially cleared lesions decreased by 42.9%. The first SDL-PDT was pain-free for 7 patients (58.3%, VAS=0). Median VAS during and after the first treatment was 0 (0.0–0.3). For the second SDL-PDT, median VAS was 0.1 (0.0–5.5, during) and 0 (0.0–4.5, after). Both SDL-PDTs were pain-free for 6 patients.ConclusionSDL-PDT was effective and nearly pain-free, emphasizing its advantages and potential for common practice.     

血啉甲醚用于光动力疗法治疗鲜红斑痣的初步临床研究

经六年大量临床验证，光动力疗法已成为具有高度选择性和稳定可靠疗效的无瘢痕治疗鲜红斑痣的新方法。为解决治疗后的较长时间皮肤光敏反应这一主要副作用，本文对２１例志愿鲜红斑痣患者的２６个病灶应用血啉甲醚（ＨＭＭＥ）为光敏剂进行了治疗，对ＨＭＭＥ的作用进行了临床观察，发现ＨＭＭＥ具有良好的疗效、较轻的局部反应、较短的避光期和可行重复治疗的间隔期等优点，值得对其进行深入的研究。     

光动力疗法治疗鲜红斑痣1216例临床分析

目的：分析比较血啉甲醚（HMME）与血卟啉衍生物（HpD)为光敏剂行光动力疗法（PDT）鲜红斑痣的临床疗效及副反应。材料与方法：鲜红斑痣患者1216例,粉红型13．2％,紫红型68．3％,增厚型18．4％。静脉注射HpD或HMME3－7mg/kg后给予铜蒸气激光、KTDS／532激光或氩离子激光照射,功率密度50－100mW/cm^2,能量密度90－540J／cm^2,随访观察。结果：HMME－PDT和HpD－PDT对各型鲜红斑痣均能有效地消除病变颜色,所随访的1632个病灶在2个月至9年的随访期内末见复发。治疗后反应有：局部水肿5－7天,部分患者有结痂或一过性色素沉着,皮肤暂时性光过敏反应。HpD－PDT组避光期30－90天,HMME－PDT组占光期7－14天,与HpD－PDT相比,HMME－PDT具有反应轻、愈合快、不衣反应少,安全度大、避光期短、色素沉着轻、护理容易、重复治疗间隔期短的特点。结论：HMME－PDT与HpD－PDT都能有效治疗各型鲜红斑痣,但HMME－PDT具有不良反应少、安全度大,避光期短、护理容易、重复治疗间隔期短等优点。     

光动力疗法联合局部化疗治疗上消化道癌的研究

为了提高光动力疗法（ＰＤＴ）的治癌效果，应用ＰＤＴ与瘤内注射氟尿嘧啶（５－Ｆｕ）治疗小鼠前胃癌移植瘤。治疗后各组移植瘤细胞ＤＮＡ含量和标记指数（ＬＩ）均较治疗前明显减少，而联合治疗组的减少较单纯ＰＤＴ或瘤内注射５－Ｆｕ组更为显著。又应用ＰＤＴ治疗进展期食管、贲门癌患者８０例，并对其中４０例联合应用内镜下局部注射５－Ｆｕ。结果：ＰＤＴ组的近期显效率为２２．５％（９／４０），联合治疗组显效率为４５．０％（１８／４０），高于ＰＤＴ组（Ｐ＜０．０５）。病例随访１２月～１８月，联合治疗组的平均生存期（３７４天）较ＰＤＴ组（２６６天）延长（Ｐ＜０．０１）。认为ＰＤＴ与局部注射５－Ｆｕ联合治疗上消化道癌，能协同提高ＰＤＴ的治疗效果。     

History of photodynamic therapy in Great Britain

Although the concept photodynamic therapy has been recognised for over a century, it is only over the last 25 years that it has been used in Great Britain. The first applications in the UK were in 1981 by John Carruth, who treated patients with advanced ENT and skin cancers. The following year, he and Stephen Bown set up the British Medical Laser Association (BMLA). Since that time, the use of PDT in the UK has slowly expanded in all fields of medicine and surgery. In 1986, Bown set up the National Medical Laser Centre (NMLC) and later collaborated with Liverpool gastroenterologist, Neville Krasner, in animal studies on rat colon. In 1997, Keyvan Moghissi founded the Yorkshire Laser Centre (YLC) and began treating patients with advanced inoperable bronchial and oesophageal cancers. Stan Brown in Leeds set up the Centre for Photobiology and Photodynamic Therapy at the University of Leeds, working in close collaboration with the Yorkshire Cancer Research Centre. Other pioneers include Hugh Barr in Gloucester, Colin Hopper in London, Grant Fullarton in Glasgow and Roger Ackroyd, Malcolm Reed and Nicky Brown in Sheffield. PDT has now been used in the UK in the treatment of skin, oral, ENT, oesophageal, lung, bladder and gynaecological malignancies.