Methyl Aminolevulinate Photodynamic Therapy Research Articles

Sequential Treatment of Superficial Basal Cell Carcinomas With Topical Methyl Aminolevulinate Photodynamic Therapy and Imiquimod 5% Cream: A Retrospective Study of Clinical and Cosmetic Outcomes.

Topical photodynamic therapy (PDT) and imiquimod 5% (IMQ) cream are established treatments for superficial basal cell carcinoma (sBCC). Both have high initial response rates and recurrence rates of up to 37%. Recent studies demonstrate that PDT and imiquimod may act on sBCCs via synergistic immunomodulatory pathways. To describe the sequential use of MAL-PDT and imiquimod 5% cream in the treatment of sBCCs and report treatment tolerability, cosmetic outcomes, and efficacy. This is a retrospective case series of patients presenting over a 2-year period with primary sBCC who underwent 2 cycles of topical MAL-PDT, followed by 6 weeks of imiquimod 5% cream. Outcome measures were resolution of the index lesion at 3 months, side effects, cosmetic outcome, and long-term recurrence (LTR). A total of 17 consecutive patients (n = 17) with a combined 21 sBCCs (n = 21) were included. The median length of follow-up was 72 months (range 24-95 months). Long-term recurrence occurred in 2/21 lesions (10%). Sequential use of PDT and imiquimod was well tolerated with good cosmetic outcomes. The 10% LTR rate is at the lower end of the range reported for single modality treatment; however, larger samples are required to evaluate efficacy differences.

Biomarkers of basal cell carcinoma resistance to methyl-aminolevulinate photodynamic therapy.

BackgroundMethyl-aminolevulinate photodynamic therapy (MAL-PDT) is an excellent option for the treatment of basal cell carcinoma (BCC). However, up to 25% of cases are resistant to this treatment modality.ObjectiveThe aim of this study was to identify potential biomarkers of BCC response to MAL-PDT.Material and methodsClinical, histological, and immunohistochemical (p53, Ki-67, CD-31, COX2, β-catenin, EGFR, and survivin) variables were analyzed in a retrospective study of consecutive BCC patients treated with MAL-PDT at the San Jorge Hospital, Huesca, Spain between January 2006 and December 2015. To deepen on these markers, the effects on p53 and cyclin D1 expression, in vitro response to MAL-PDT of 2 murine BCC cell lines (ASZ and BSZ), was also evaluated.ResultsThe retrospective study examined the response to MAL-PDT of 390 BCCs from 182 patients. The overall clinical response rate was 82.8%, with a mean follow-up time of 35.96 months (SD = 23.46). Immunohistochemistry revealed positive p53 in 84.6% of responders but only 15.4% of nonresponsive tumors (p = 0.011). Tumors with increased peripheral palisading of basal cell islands to immunostaining β-catenin responded poorly to PDT (p = 0.01). In line with our findings in patients, in vitro studies revealed a better response to PDT in the p53-positive ASZ cell line than the p53-negative BSZ cell line (p<0.01).Multivariate analysis revealed that the following variables were significantly associated with response to PDT: age, nBCC, presence of peritumoral inflammatory infiltrate, and p53 immunopositivity. Patients with positive p53 immunostaining were 68.54 times more likely to achieve cure than p53-negative patients (CI95% 2.94–159.8)ConclusionOur finding suggest that certain clinicopathological and immunohistochemical variables, particularly p53 expression, may serve as indicators of BCC response to MAL-PDT, and thus facilitate the selection of patients who are most likely to benefit from this therapy.

Randomized Trial of Four Treatment Approaches for Actinic Keratosis

BackgroundActinic keratosis is the most frequent premalignant skin disease in the white population. In current guidelines, no clear recommendations are made about which treatment is preferred.MethodsWe investigated the effectiveness of four frequently used field-directed treatments (for multiple lesions in a continuous area). Patients with a clinical diagnosis of five or more actinic keratosis lesions on the head, involving one continuous area of 25 to 100 cm2, were enrolled at four Dutch hospitals. Patients were randomly assigned to treatment with 5% fluorouracil cream, 5% imiquimod cream, methyl aminolevulinate photodynamic therapy (MAL-PDT), or 0.015% ingenol mebutate gel. The primary outcome was the proportion of patients with a reduction of 75% or more in the number of actinic keratosis lesions from baseline to 12 months after the end of treatment. Both a modified intention-to-treat analysis and a per-protocol analysis were performed.ResultsA total of 624 patients were included from November 2014 through March 2017. At 12 months after the end of treatment, the cumulative probability of remaining free from treatment failure was significantly higher among patients who received fluorouracil (74.7%; 95% confidence interval [CI], 66.8 to 81.0) than among those who received imiquimod (53.9%; 95% CI, 45.4 to 61.6), MAL-PDT (37.7%; 95% CI, 30.0 to 45.3), or ingenol mebutate (28.9%; 95% CI, 21.8 to 36.3). As compared with fluorouracil, the hazard ratio for treatment failure was 2.03 (95% CI, 1.36 to 3.04) with imiquimod, 2.73 (95% CI, 1.87 to 3.99) with MAL-PDT, and 3.33 (95% CI, 2.29 to 4.85) with ingenol mebutate (P≤0.001 for all comparisons). No unexpected toxic effects were documented.ConclusionsAt 12 months after the end of treatment in patients with multiple actinic keratosis lesions on the head, 5% fluorouracil cream was the most effective of four field-directed treatments. (Funded by the Netherlands Organization for Health Research and Development; ClinicalTrials.gov number, NCT02281682.)

MAL-PDT inhibits oral precancerous cells and lesions via autophagic cell death.

Oral cancer is a common cancer with a high mortality rate. While surgery is the most effective treatment for oral cancer, it frequently causes deformity and dysfunction in the orofacial region. In this study, methyl aminolevulinate photodynamic therapy (MAL-PDT) as a prevention tool against progression of precancerous lesion to oral cancer was explored. For in vitro studies, we evaluated the effects of MAL-PDT on viability of DOK oral precancerous cells by XTT, cell morphology by TEM, and intracellular signaling pathways by flow cytometry, Western blotting, and immunofluorescence. For in vivo study, DMBA was used to induce oral precancerous lesions in hamsters followed by MAL-PDT treatment. We measured tumor size and body weight weekly. After sacrifice, buccal pouch lesions were processed for H&E stain and immunohistochemistry analysis. MAL-PDT induced autophagic cell death in DOK oral precancerous cells. The autophagy-related markers LC3II and p62/SQSTM1 and autophagosome formation in DOK cells were increased after MAL-PDT treatment. In vivo, Metvix® -PDT treatment decreased tumor growth and enhanced LC3II expression in hamster buccal pouch tumors induced by DMBA. Our in vitro and in vivo results suggest that MAL-PDT may provide an effective therapy for oral precancerous lesions through induction of autophagic cell death.

Topical Methyl Aminolevulinate Photodynamic Therapy in Porokeratosis of Mibelli: An Alternative Treatment for a Refractory Disease.

Topical Methyl Aminolevulinate Photodynamic Therapy in Porokeratosis of Mibelli: An Alternative Treatment for a Refractory Disease.

Histologic subtype of treatment failures after noninvasive therapy for superficial basal cell carcinoma: An observational study

There have been concerns that recurrences after noninvasive therapy for basal cell carcinoma (BCC) transform into a "more aggressive" histologic subtype. We sought to evaluate the proportion of patients with a nonsuperficial treatment failure after noninvasive therapy for superficial BCC. An observational study was performed using data from a single blind, noninferiority, randomized controlled trial (March 2008-August 2010) with 5-year follow-up in patients with primary superficial BCC treated with methylaminolevulinate-photodynamic therapy, 5-fluorouracil, or imiquimod. Data were used from 166 adults with a histologically confirmed treatment failure. A nonsuperficial subtype was found in 64 of 166 treatment failures (38.6%). Proportions with a more aggressive subtype than the primary tumor were 51.3% (38/74) for early and 28.3% (26/92) for later treatment failures (P=.003). The proportion of more aggressive early failures was significantly lower after imiquimod (26.3%) compared with methylaminolevulinate-photodynamic therapy (54.8%, P=.086) and 5-fluorouracil (66.7%, P=.011). There was limited information on the exact time of occurrence of treatment failures. More aggressive treatment failure recurrences after noninvasive therapy for superficial BCC occur most often within the first 3months posttreatment, probably indicating underdiagnosis of more aggressive components in the primary tumor rather than transformation.

Is a single day patient friendly methyl aminolevulinate photodynamic therapy illumination scheme for superficial basal cell carcinoma feasible? A randomized multicenter pilot trial

Background: Topical methyl aminolevulinate photodynamic therapy (MAL-PDT) is highly effective for the treatment of superficial basal cell carcinoma (sBCC). Current European treatment protocol requires two hospital visits, which is costly and unpractical. The aim of this study was to evaluate the efficacy of fractionated MAL-PDT, using two light fractions at 3 and 4 h compared to illumination at 3 and 5 h after MAL-application.Methods: Thirty patients were randomized into two groups. The first group received illumination at 3 and 4 h (20 + 55 J/cm2) after MAL-application (3/4 group). In the other group, two light fractions were performed at 3 and 5 h (20 + 55 J/cm2) after MAL-application (3/5 group). The lesion response was evaluated at 3 and 12 months posttreatment.Results: In the 3/5 group, 70.0% showed a complete response (CR) at 3 months compared to 63.6% in the other group. At 12 months, 100% showed a CR in the 3/5 group compared to 80.0% in the other group. However, most failures/recurrences were eventually due to the presence of a more aggressive BCC subtype, mostly caused by sampling error of the primary punch biopsy.Conclusion: Single day protocol for MAL-PDT for sBCC is feasible and this study shows promising results.

Ablative fractional laser–assisted photodynamic therapy provides superior long-term efficacy compared with standard methyl aminolevulinate photodynamic therapy for lower extremity Bowen disease

Ablative fractional laser (AFL)-assisted methyl aminolevulinate (MAL) photodynamic therapy (PDT) (AFL-MAL-PDT) has shown significantly higher efficacy and lower recurrence rates at 12months than conventional methyl aminolevulinate photodynamic therapy (MAL-PDT) for the treatment of Bowen disease (BD). However, long-term follow-up data are not available. To compare the 5-year efficacy and recurrence rates of AFL-MAL-PDT with those of conventional MAL-PDT for the treatment of lower extremity BD. A total of 60 patients with 84 BD lesions were randomly assigned to a single session of AFL-MAL-PDT or 2 sessions of MAL-PDT with a 1-week interval between sessions. Patients were followed up at 3, 12, 24, 36, 48, and 60months after treatment. Efficacy, recurrence rates, and risk factors for unsuccessful treatments were assessed. After 5years, the overall clearance rate of AFL-MAL-PDT (84.78%) was significantly better than that of MAL-PDT (44.74%) for BD lesions. The recurrence rate was significantly lower for AFL-MAL-PDT (9.3%) than for MAL-PDT (41.38%). Diameters larger than 20mm and lesions with a history of previous treatment were independent factors for treatment failure. The small sample size and single-center study design were limitations. For patients with lower extremity BD lesions, AFL-MAL-PDT showed significantly higherlong-term efficacy and lower recurrence rates than standard MAL-PDT.

Photodynamic therapy corrects abnormal cancer-associated gene expression observed in actinic keratosis lesions and induces a remodeling effect in photodamaged skin

BackgroundActinic keratoses (AK) are proliferations of neoplastic keratinocytes in the epidermis resulting from cumulative exposure to ultraviolet radiation (UVR), which are liable to transform into squamous cell carcinoma (SCC). Organ Transplant Recipients (OTR) have an increased risk of developing SCC as a consequence of long-term immunosuppressive therapy. The aim of this study was to determine the molecular signature of AKs from OTR prior to treatment with methyl aminolevulinate-photodynamic therapy (MAL-PDT), and to assess what impact the treatment has on promoting remodeling of the photo-damaged skin. MethodsSeven patients were enrolled on a clinical trial to assess the effect of MAL-PDT with biopsies taken at screening prior to the first treatment session (week 1), and six weeks after completion of final treatment (week 18). Whole-genome gene expression analysis was carried out on skin biopsies isolated from an AK lesion, an area surrounding the lesion, and a non-sun exposed region of the body. Quantitative PCR was utilized to confirm the differential expression of key genes. ResultsMAL-PDT treatment corrected abnormal proliferation-related gene profiles, corrected aberrantly expressed cancer-associated genes and induced expression of dermal extracellular matrix genes in photo-exposed skin. ConclusionThe efficacy of the MAL-PDT on AK lesions was confirmed at whole-genome gene expression level. A transcriptional signature of remodeling, identified through assessing the effect of MAL-PDT on photodamaged skin, supports the use of MAL-PDT for treating photodamaged skin and field cancerized areas.

Comparing Topical Treatments for Basal Cell Carcinoma

Superficial basal cell carcinoma is a type of keratinocyte carcinoma that has increasing incidence and substantial morbidity. Jansen etal. report on a randomized trial with 5 years of follow-up that found imiquimod to be more effective than 5-fluorouracil or methyl aminolevulinate photodynamic therapy in preventing superficial basal cell carcinoma recurrence. However, the toxicity and cost of topical treatments, as well as patient preferences, need to be evaluated when making treatment decisions in clinical practice.

Folliculotropic Mycosis Fungoides in 20 Korean Cases: Clinical and Histopathologic Features and Response to Ultraviolet A-1 and/or Photodynamic Therapy.

BackgroundFolliculotropic mycosis fungoides (FMF) is a variant of mycosis fungoides (MF) that is characterized clinically by variable types of skin eruptions, including plaques, acneiform lesions, and alopecic patches. Histopathologically, FMF is characterized by folliculotropic infiltrates.ObjectiveThis study was conducted to scrutinize the clinical and histopathologic features of FMF in Koreans and the responses to phototherapy.MethodsTwenty Koreans diagnosed with MF who had histopathologic evidence of folliculotropism were enrolled.ResultsEighteen patients had head-and-neck-region infiltration, while five had solitary lesion. In all patients, the atypical lymphocytic infiltrate had a perifollicular distribution. Twelve patients were treated with ultraviolet A (UVA)-1. Eleven of these 12 patients with early-stage FMF experienced >80% improvement (8: complete remission; 3: partial remission). Four patients, including 2 who relapsed after UVA-1, were treated with photodynamic therapy (PDT), reaching complete remission after PDT.ConclusionAs FMF has variable clinical presentations, skin biopsy is required to confirm the diagnosis. And both UVA-1 and methyl aminolevulinate-PDT are clinically effective in treatment of early-stage FMF.

Five-Year Results of a Randomized Controlled Trial Comparing Effectiveness of Photodynamic Therapy, Topical Imiquimod, and Topical 5-Fluorouracil in Patients with Superficial Basal Cell Carcinoma

For the treatment of superficial basal cell carcinoma, a prospective, noninferiority, randomized controlled multicenter trial with 601 patients showed that 5% imiquimod cream was superior and 5-fluorouracil cream not inferior to methyl aminolevulinate photodynamic therapy (MAL-PDT) at 1 and 3 years after treatment. No definite conclusion could be drawn regarding the superiority of imiquimod over 5-fluorouracil. We now present the 5-year follow-up results according to the intention-to-treat analysis. Five years after treatment, the probability of tumor-free survival was 62.7% for methyl aminolevulinate photodynamic therapy (95% confidence interval [CI]= 55.3-69.2), 80.5% for imiquimod (95% CI= 74.0-85.6), and 70.0% for 5-fluorouracil (95% CI= 62.9-76.0). The hazard ratio for treatment failure of imiquimod and 5-fluorouracil were 0.48 (95% CI= 0.32-0.71, P < 0.001) and 0.74 (95% CI= 0.53-1.05, P= 0.09), respectively, when compared with methyl aminolevulinate photodynamic therapy. Compared with 5-fluorouracil, imiquimod showed a hazard ratio of 0.65 (95% CI 0.43-0.98, P= 0.04). In conclusion, 5 years after treatment, the results of this trial show that 5% imiquimod cream is superior to both methyl aminolevulinate photodynamic therapy and 5-fluorouracil cream in terms of efficacy for superficial basal cell carcinoma. We therefore consider 5% imiquimod cream as the first choice for noninvasive treatment in most primary superficial basal cell carcinomas.

Clinicopathological features of Bowen’s disease resistance to methyl aminolevulinate photodynamic therapy

Clinicopathological features of Bowen’s disease resistance to methyl aminolevulinate photodynamic therapy

Photodynamic therapy in the management of basal cell carcinoma: Retrospective evaluation of outcome

IntroductionPhotodynamic therapy (PDT) is a relatively new method of treating various kinds of pathologies. In this retrospective study, a total of 148 patients with basal cell carcinoma (BCC) were treated with surface illumination methyl aminolevulinate – photodynamic therapy (MAL-PDT) or meta-tetrahydroxyphenylchlorin (mTHPC-PDT). Comparisons with the clinical features, rate of recurrence and overall outcome were made. Materials and methodsSurface illumination PDT was offered under local or general anaesthesia. For thin BCCs, the 16% strength cream (MAL) was applied topically 3h prior to tissue illumination. A single-channel 628nm diode laser was used for illumination and light was delivered at 100J/cm2 per site. For thick BCCs, 0.05mg/kg mTHPC was administered intravenously prior to tissue illumination. A single-channel 652nm diode laser was used for illumination and light was delivered at 20J/cm2 per site. Lesion response evaluation was carried out according to RECIST. ResultsThe MAL-PDT sub-group included 86 patients with 127 thin BCCs; 80 patients had complete response (CR) after one round of treatment. The mTHPC-PDT sub-group included 62 patients with 116 thick BCCs; 60 patients had complete response after one round of treatment. Statistically significant factors associated with complete response to MAL-PDT included superficial BCC histotype (P<0.001), ≤0.5mm tumour thickness (P<0.001) and lack of ulceration (P<0.001). While for the mTHPC-PDT sub-group, both superficial and nodular types responded significantly better than invasive type (P<0.001); the lack of ulceration was insignificant factor in achieving complete response. ConclusionPDT achieved high efficacy in the treatment of basal cell carcinomas with greatly reduced morbidity and disfigurement. The technique is simple, can commonly be carried out in outpatient clinics, and is highly acceptable to patients.

Observational study of chondrodermatitis nodularis helicis treated with methyl aminolevulinate photodynamic therapy

Therapies used to treat chondrodermatitis nodularis helicis (CNH), such as surgical excision, pressure relief, or topical steroids report varying degrees of success. We evaluated the response and safety of methyl aminolevulinate (MAL) photodynamic therapy (PDT) in CNH. This retrospective, observational study performed at the University Hospital Ramon y Cajal (Madrid, Spain) and Hospital San Jorge (Huesca, Spain) included all patients diagnosed with CNH and treated with MAL-PDT from 2008 to 2015. Treatment sites were prepared and irradiated as per the conventional MAL-PDT procedure. Patients underwent a mean of 2.3 sessions with between-session intervals ranging from 15days to 1month. A complete response to PDT was observed in 33 patients (76.7%), who experienced pain relief and resolution of the inflammatory nodule. Lesion recurrence was recorded in 10 patients (23.3%) during the mean follow-up period of 20months. Receiving ≥2 PDT sessions was significantly associated with a good response (26/28, 93% success rate, P=.003). Some limitations of the study are the lack of an established between-session interval, the absence of evaluation of curettage effectiveness and the limited sample size. The results support the view that PDT is a promising treatment approach for CNH.

Effect of Methyl Aminolevulinate Photodynamic Therapy With and Without Ablative Fractional Laser Treatment in Patients With Microinvasive Squamous Cell Carcinoma

Surgical excision is the standard treatment for cutaneous squamous cell carcinoma (SCC). However, microinvasive SCC (Clark level II) is limited to the papillary dermis, and it should be differentiated from invasive SCC. Ablative fractional laser-primed photodynamic therapy (AFL-PDT) may have enhanced efficacy. To compare 1 session of AFL-PDT with 2 sessions of conventional methyl aminolevulinate-PDT (MAL-PDT) for the treatment of microinvasive SCC. A 2-armed, randomized, single-blind, comparative trial of 45 patients with histologically proven microinvasive SCC. Twenty-one patients were randomized to treatment with a single AFL-PDT session, and 24 patients were randomized to 2 MAL-PDT sessions with a 1-week interval between sessions using a computer-generated program. Standard pretreatment such as curettage was not performed prior to PDT owing to a tendency to bleed. The efficacy, recurrence rate, cosmetic outcomes, and safety were assessed 1 week, 3, 12, and 24 months after the last treatment. AFL was performed with an ablation depth of 550 µm to 600 µm, coagulation level of 1, treatment density of 22%, and a single pulse. Then, MAL cream was applied under occlusion for 3 hours and illuminated by using a red light-emitting diode light at 37 J/cm2. A second session of MAL-PDT was administered after 7 days. The primary outcome measures were the lesion response at 3 and 12 months, and the recurrence rate 12 months after the last treatment. Twenty-one patients (6 men, 15 women) with a mean (SD) age of 76 (6) years were randomized to treatment with a single AFL-PDT session, and 24 patients (11 men, 13 women) with a mean (SD) age of 75 (6) years were randomized to 2 MAL-PDT sessions. The overall complete response rates 3 months after treatment were 84.2% with AFL-PDT and 52.4% with MAL-PDT (P = .03). These differences in efficacy remained significant at the 24-month follow-up. The recurrence rate was significantly lower with AFL-PDT (12.5%) than with MAL-PDT (63.6%) at 24 months (P = .006). AFL-PDT and MAL-PDT did not differ significantly with respect to the cosmetic outcomes, adverse events, or pain intensity. AFL-PDT can be used as an alternative treatment option for patients with microinvasive SCC who are not suitable for surgical treatment. clinicaltrials.gov Identifier: NCT02666534.

PDT for onychomycosis.

In this issue, Gilaberte et al. present data on methyl aminolevulinate–photodynamic therapy (MAL-PDT) for onychomycosis. Poor treatment results and evolving drug resistance with the conventional topical and systemic antifungal drugs have initiated a search for alternative treatments, and PDT is such an alternative. There are several reports on successful use of PDT for onychomycosis in the literature.1, 2 The treatment results with MAL-PDT in Gilaberte et al.'s study are poor, and not different from placebo. Onychomycosis without total dystrophy, however, responded better to MAL-PDT and was associated with a higher microbial cure rate than placebo-PDT and showed a better clinical outcome as measured using the onychomycosis severity index. Twenty-four weeks after initial MAL-PDT, three of nine dermatophyte-infected had achieved microbial cure, but at the end of the study, at week 36, positive dermatophyte cultures had increased to eight. As MAL is not in itself a photosensitizer but needs to be taken up and metabolized to photoactive porphyrins, a necessary capability of a susceptible fungus is that it has uptake capacity and an enzymatic repertoire capable of converting MAL to photoactive porphyrins. This capability was demonstrated for Trichophyton rubrum in laboratory studies, and aminolevulinate–PDT was shown to have growth-inhibiting effect.3 Gilaberte et al. cultured 10 different species of fungi in their study, and the question arises whether all these species have the same capabilities as shown for Trichophyton rubrum. There might be differences which have considerable influence on their susceptibility to MAL-PDT. Further studies are needed to elucidate this. Treatment of onychomycosis is difficult, and recurrences are the rule rather than the exception. No fungal resistance and genotoxic or mutagenic effect to fungus or human cells have so far been reported using PDT with various photosensitizers.1 It therefore seems to be a safe therapy option which can be used in selected cases.

Comparison of “Lesion-by-Lesion” and Field Photodynamic Therapy in the Prevention of Actinic Keratoses: A Randomized, Split-Face, Single-Blind Pilot Study

Background: Actinic keratoses (AKs) are often treated separately, lesion by lesion. However, in the past years, AKs have been described as a field disease and not limited to single clinically apparent lesions. Treatment should therefore target an area of field change which may reduce the risk of development of further AKs, second tumours, and local recurrence. Objective: The primary objective was to determine the number of new lesions at 9 months after methyl aminolevulinate photodynamic therapy (MAL-PDT). Secondary objectives were to determine the number of new lesions at 3 and 6 months after treatment and the percentage reduction of AKs from baseline at 3, 6, and 9 months after MAL-PDT. Methods: This was a single-centre, prospective, randomized, split-face, investigator-blinded pilot study with a study duration of 1 year. The study population comprised patients with AKs on the face or scalp, with a maximum of 10 AKs on each side. One side was treated with 1 session of “lesion-by-lesion” MAL-PDT (LT side) and the other side with 1 session of field MAL-PDT (FT side). Results: At 9 months the FT demonstrated significantly fewer new lesions. At every time point during the follow-up, we found a significant reduction in the number of AKs in the LT as well as in the FT sides. After 3 and 6 months we did not observe significant differences between the sides. However, after 9 months, the LT area showed significantly fewer remaining AKs, whereas the FT area demonstrated significantly fewer new lesions. Conclusions: Field treatment results in significantly fewer new AK lesions compared with lesion-by-lesion treatment.

Methyl aminolevulinate photodynamic therapy for onychomycosis: a multicentre, randomized, controlled clinical trial

Onychomycosis is a common fungal nail infection that responds poorly to antifungals. To investigate the efficacy and safety of methyl aminolevulinate (MAL) photodynamic therapy (PDT) in the treatment of onychomycosis. A multicentre (3), randomized, placebo-controlled clinical trial compared the effects of three sessions of urea (40%) plus conventional MAL-PDT with urea (40%) plus placebo (red light) photodynamic therapy (pPDT) in onychomycosis patients. Efficacy, both clinical (onychomycosis severity index, OSI) and microbiological, was blindly evaluated after 36 weeks of follow-up. Forty patients were analysed in the trial. Twenty-two received MAL-PDT and 18 pPDT. A complete response (OSI = 0) was observed for four patients (18.18%) in the MAL-PDT group and one (5.56%) in the pPDT group (NTT 7.92, 95% CI: 2.98-9.69, P = 0.23). A decrease in OSI score of over 75% (OSI75) was achieved by 40.91% of the patients in the MAL-PDT group and 16.67% in the pPDT group (P = 0.096). Microbiological cure was achieved by seven patients (31.82%) in the MAL-PDT group and two (11.11%) in the pPDT group (P = 0.178). MAL-PDT resulted in better rates of clinical response [OSI >75%: 53.85% vs. 18.75% (P =0.048)] and microbiological cure [41.56% vs. 7.14% (P = 0.037)] in non-dystrophic vs. dystrophic onychomycosis patients. No significant side-effects were reported. The limitations of the study were the reduced sample size and the unexpected efficacy of the control treatment, which was attributed to the 40% urea pre-treatment. This study did not show significant differences between urea 40% + MAL-PDT and urea 40% + pPDT in the treatment of onychomycosis. However, some results suggest that this treatment may constitute an alternative for dermatophyte and non-dermatophyte mould onychomycosis in patients not eligible for systemic treatment, particularly in the absence of total nail dystrophy.

Erythroplasia of Queyrat treated by laser and light modalities: a systematic review.

Erythroplasia of Queyrat (EOQ) is a squamous cell carcinoma in situ most commonly located on the glans penis or prepuce. EOQ accounts for roughly 10% of all penile malignancies and may lead to invasive squamous cell carcinoma. Standard therapy includes local excision, partial or total penectomy, cryotherapy, and topical cytotoxic agents. Treatment of EOQ has proven to be challenging due to low response rates and recurrence. In addition, radical procedures can significantly affect sexual function and quality of life. Alternative laser treatments and photodynamic therapy (PDT) offer promising results for treating EOQ. A systemic review of the literature was performed for articles discussing laser and light therapy for EOQ. Among the patients treated with the CO2 laser, 81.4% of cases had complete remission after one session of treatment. Patients treated with PDT presented with more variable results, where 62.5% of those treated with methyl aminolevulinate photodynamic therapy (MAL-PDT) achieved complete remission. Aminolevulinic acid (ALA-PDT) treatment showed a similar rate of remission at 58.3%. One study utilized the Nd:YAG laser, which resulted in a recurrence of the lesion in four of the five patients treated. Of the methods reviewed, the CO2 laser offered the most promising results with a cosmetically excellent prognosis. Further studies with larger power and longer follow-up times are needed to determine the optimal treatment regimen for this penile malignancy.