Photodynamic therapy effective for the treatment of actinic keratosis and basal cell carcinoma in bullous pemphigoid patients

Treating skin cancers and extensive actinic keratosis in patients with bullous pemphigoid (BP) can be challenging. Treatment options pose unique risks in these patients as surgical wounds can have delayed wound healing and photodynamic therapy (PDT) may exacerbate their blistering disease. We report the successful use of PDT to treat actinic keratosis and skin cancers in two patients with BP, both of whom had excellent response to PDT and tolerated treatment without any bullous disease flares. Carefully selected patients with skin cancers and stable, well controlled BP can be safely considered for treatment using PDT.     

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.     

Efficacy of iontophoresis-assisted ablative fractional laser photodynamic therapy with short incubation time for the treatment of actinic keratosis: 12-month follow-up results of a prospective,randomised, comparative trial

BackgroundIontophoresis is a transdermal drug-delivery technique that enhances the transport of ionic species across membranes and may have significant benefit for the treatment of actinic keratosis (AK) by ablative fractional laser–primed photodynamic therapy (AFL-PDT). The aims of this study were to compare the efficacy, recurrence rate, cosmetic outcome and safety of iontophoresis-assisted AFL-PDT with 2 h of incubation vs. those of conventional AFL-PDT with 2- and 3-h incubation in patients with facial and scalp AK.MethodsPatients were randomly assigned to iontophoresis-assisted AFL-PDT with a 2-h incubation time (group A) and conventional AFL-PDT with a 2-h (group B) and 3-h (group C) incubation time. All patients underwent AFL-PDT, and group A patients were assigned to treatment with iontophoresis after methyl-aminolevulinate (MAL) application. After 2 or 3 h, MAL-applied lesions were irradiated using a red light. Patients were followed up at 1-week, 3 months and 12 months after treatment. Efficacy, cosmetic outcomes and adverse events were assessed.ResultsIn total, 41 patients (160 AK lesions) completed the study and were evaluated. Efficacy was significantly higher in Group A (88.7%) than in Group B (73.2%); the efficacy of groups A and C (92.2%) at 3 months follow-up was comparable. The recurrence rates were not significantly different between the groups at 12 months (P = 0.841). The three groups did not differ in terms of cosmetic outcomes and safety.ConclusionsIontophoresis-assisted AFL-PDT showed higher efficacy than AFL-PDT with short incubation time. Iontophoresis may effectively reduce the incubation time in AFL-PDT.     

A randomized split-face clinical trial analyzing daylight photodynamic therapy with methyl aminolaevulinate vs ingenol mebutate gel for the treatment of multiple actinic keratoses of the face and the scalp

IntroductionDaylight photodynamic therapy with methyl aminolaevulinate (dlPDT) and ingenol mebutate gel (IMB) are approved therapeutic options for multiple actinic keratoses (AKs).The aim of this comparative, intra-patient, split-face, randomized clinical trial was to compare treatment outcomes of dlPDT and IMB.MethodsTwo symmetrical contralateral areas of 25 cm², harboring a similar (5–10) number of AKs, were selected and randomly assigned either to a 3 days’ IMB treatment cycle or to a single session of dlPDT. The day after the local skin reaction (LSR) score was registered. Patients’ scored pain (assessed through VAS method) after the treatment, and time needed for wound closure, were subsequently registered. After 90 days, the complete remission (CR) rate recorded for both single lesions and patients, the cosmetic outcome and the patients’ preference, were assessed.Results22 patients with a total of 311 AKs were enrolled. The mean pain VAS score was 3.55 ± 1.82 with IMB and 2.05 ± 0.72 with dlPDT (p < 0.01). The mean LSR score was 9.91 ± 4.24 and 4.59 ± 4.03 (p < 0.01), respectively. The mean days necessary for wound closure were 9.45 ± 3.51 and 4.36 ± 1.18 days (p < 0.01), respectively. After 3 months, 119 lesions with IMB and 120 lesions with dlPDT were healed and the CR rate with IMB (75.8%) was non-inferior to the CR rate with dlPDT (77.9%). The comparisons of CR rates of grade I and II AKs did not show any inferiority for one treatment compared to the other. Eight patients (36.4%) had all lesions cleared with IMB and 7 (31.8%) with dlPDT (p = NS). The cosmetic outcome was better with dlPDT and 17 patients evaluated dlPDT as their preferred treatment.ConclusionsA 3 days’ treatment cycle with IMB and a single session of dlPDT had a similar efficacy for both grade I AKs and grade II AKs but dl PDT showed lower pain and inflammation scores, quicker wound closure, better cosmetic outcome and higher patients’ preference.     

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.     

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 in the palliative treatment of esophageal cancer

Esophageal carcinoma is one of the most common cancers in the world and has an increasing incidence in Western civilisation and poor prognosis. In most cases palliative treatment is the only kind of therapy, which can be applied.In the Department of Digestive Tract Diseases, Medical University, Lodz, Poland, we have used PDT in two cases of palliative therapy of advanced esophageal cancer in cervical location of esophagus.We find PDT very promising, minimally invasive, safe and easy technique to perform for esophageal cancer of cervical localization.     

Effect of 5-aminolevulinic acid photodynamic therapy on Candida albicans biofilms: An in vitro study

BackgroundIn this study, the photoinactivation of 5-aminolevulinic acid (ALA) has been investigated on Candida albicans biofilms in vitro.MethodsAfter culture and proliferation of Candida albicans biofilms in vitro, the metabolic activity was confirmed using XTT reduction assay. Then, the suitable incubation time and concentration of ALA were determined by measuring PpIX accumulation quantities. Photosensitivity of the biofilms treated with ALA solution was studied in optical doses of 50, 100, 200 and 300 J/cm² while light irradiation was applied by a red light semiconductor. Finally, rapid immunofluorescence staining method using the LIVE/DEAD FungaLight Yeast Viability Kit and XTT assay were conducted to visualize and quantify the antifungal effect of ALA-PDT on Candida albicans biofilms.ResultsA 5 h incubation time and 15 mM ALA concentration were determined for this study. Photoinactivation of ALA-PDT on Candida albicans biofilms showed a significant increase of protoporphyrin IX (PpIX) in the biofilms. The metabolic activity of Candida albicans biofilms tread with ALA-PDT confirmed the inhibition efficacy compared with control groups. Upon radiation at 300 J/cm², cells in Candida albicans biofilms were 74.45% inhibited.ConclusionsPpIX can be absorbed in biofilm-grown Candida albicans in vitro and under appropriate parameters, photochemistry can be triggered by light in combination with ALA and inhibits Candida albicans biofilms effectively.     

Molecular analysis of apoptosis pathway after photodynamic therapy in breast cancer: Animal model study

BackgroundMolecular investigation of breast tumors has permitted better understanding about interaction of genes and pathways involved in tumor progression.ObjectiveThe aim of this study was to evaluate the association between genes belonging to the pathway of apoptosis with tumor response to photodynamic therapy.Study Design/Materials and methodsThe mammary tumors were induced in twenty-four Spraguey-Dawley female rats by oral gavage of 7,12-dimethylbenz(a)anthracene (8 mg/Kg body weight). Animals were divided into three groups: G1 (normal tissue), G2 (tumors without treatment), G3 (animals euthanized 48 h after treatment). The photosensitizer used was a chlorin, 5,15-bis-(2-bromo-5-hydroxyphenyl) chlorin in the dose of 8 mg/kg for each animal. Light source of diode laser at a wavelength of 660 nm, fluence rate of 100 mW/cm, and light dose of 100 J/cm was delivery to lesions for treatment. A sample from each animal was investigated by quantitative real time PCR using Rat Apoptosis RT² Profiler™ PCR Array platform.ResultsPro-apoptotic BAK1, CARD6, CASP8, CIDEA, CIDEB, DAPK1, TNF, TNFRSF10B, FASLG, LOC687813, and TP73 genes showed increased expression, and CD40 anti-apoptotic gene showed decreased expression in the group who underwent PDT (G3) in relation to G2.ConclusionThe results indicated that these genes are involved more directly with cellular apoptosis induced by PDT using the Chlorin photosensitizer.     

A clinical evaluation of the efficacy of photodynamic therapy in the treatment of erosive oral lichen planus: A case series

BackgroundErosive oral lichen planus (EOLP) poses a substantial risk of malignant transformation into squamous cell cancer. The absence of established treatment gives way to alternative therapeutic strategies, including photodynamic therapy. The aim of the study was to evaluate the efficacy of PDT in the treatment of EOLP.MethodsTwelve female patients aged 63–80 with 22 OLP lesions (16 on the buccal mucosa, 6 on gingiva and tongue), underwent authors’ own PDT scheme with the use of 5% solution of 5-aminolevulinic acid (ALA) as photosensitizer. An ALA-saturated occlusive dressing was applied directly onto a lesion and surrounding mucosa 2 h prior to illumination with a custom-made diode lamp (light of 630 nm, dose of 300 mW). After a series of 10 weekly illumination sessions the patients were monitored for 12 months.ResultsThe mean size of lesions before treatment was 1.46 cm² ± 1.44. The lesions on the buccal mucosa were smaller (1.06 cm² ± 0.98) than those on the gingiva and tongue (2.63 cm² ± 1.93). Post-treatment improvement encompassed 16 lesions, 5 of which were in remission. The mean reduction in size after 10-session therapy was 8,05%. The healing continued and further reduction in size (by 69.13%) took place during the 12-month observation: 39.62% of lesions within the buccal mucosa and full remission of all lesions on the gingiva and tongue.ConclusionsThe results suggest that PDT offers non-invasive treatment of lesions in oral mucosa and may become an alternative and complementary method to those currently in use. Further studies involving larger groups of patients should be undertaken before it becomes routine practice.     

5-Aminolevulinic Acid Photodynamic Therapy combined with CO2 laser therapy in treatment of laryngeal papilloma: Case report

This article describes the case of 5-Aminolevulinic Acid Photodynamic Therapy (ALA-PDT) via self-retaining laryngoscope under general anesthesia combined with CO₂ Laser Therapy in the treatment of three patients with juvenile laryngeal papilloma. Laryngeal papilloma Clinically, it features rapid growth, multi-focus, frequent recurrence and possibility of spreading to the lower respiratory tract. ALA-PDT via self-retaining laryngoscope under general anesthesia combined with CO₂ Laser Therapy is safe and effective for clearing laryngeal papilloma, laryngeal papilloma was fully removed from the three patients, with no recurrence during the 6–24 months of follow-up medical examination. 5-Aminolevulinic Acid Photodynamic Therapy (ALA-PDT) via self-retaining laryngoscope under general anesthesia combined with CO₂ Laser can be used for treating laryngeal papilloma.     

Sub-additive effects of photodynamic therapy combined with erlotinib for the treatment of epidermoid carcinoma: An in vitro study

BackgroundPhotodynamic therapy (PDT) is an antitumour treatment that employs the combination of a photosensitive compound, oxygen and visible light. To improve the antitumour activity of PDT, the present study used the strategy of combining PDT with erlotinib (ERL), a drug frequently used in the treatment of epidermoid carcinoma.MethodsAn MTT cell viability assay was used to evaluate the cytotoxicity of PDT combined with ERL on A431 epidermoid carcinoma cells in vitro. This study evaluated the cytotoxicity of the following treatments: red laser irradiation (660 nm) at different power densities (1.25–180 J/cm²), the photosensitizer methylene blue (MB) at concentrations of 0.39–100 μM, PDT (12.5 μM MB and laser power densities from 1.25 to 180 J/cm²), and PDT (12.5 μM MB and a laser density of 120 J/cm²) plus ERL (1 μM).ResultsThe laser power densities that were tested showed no cytotoxicity in A431 cells. MB showed a dose-dependent cytotoxicity. In PDT, an increase in the dose of light resulted in an increase in the cytotoxicity of MB. In addition, there was a sub-additive effect between PDT and ERL compared to the effect of each therapy alone.ConclusionsThe sub-additive effect between PDT and ERL suggests that their combination may be an important strategy in the treatment of epidermoid carcinoma.     

Role of antimicrobial photodynamic therapy in the treatment of aggressive periodontitis: A systematic review

BackgroundThe aim was to assess the efficacy of antimicrobial photodynamic therapy (aPDT) in the treatment of aggressive periodontitis (AgP).MethodsThe addressed focused question was “Is aPDT effective in the treatment of AgP?” MEDLINE/PubMed, EMBASE, Scopus, ISI Web of knowledge and Google-Scholar databases were searched from 1977 till May 2015 using combinations of the following keywords: antimicrobial; photochemotherapy; photodynamic therapy; photosensitizing agents; AgP; scaling and root-planing (SRP). Reviews, case reports, commentaries, and articles published in languages other than English were excluded.ResultsSeven studies were included. In 5 studies, aPDT was performed as an adjunct to SRP. Laserwavelengths and duration of irradiation ranged between 660–690 nm and 60–120 s, respectively. Laser power output as reported in 2 studies was 75 mW. One study showed significant improvement in periodontal parameters for subjects receiving aPDT as an adjunct to SRP as compared to treatment with SRP alone at follow up. However, comparable periodontal parameters were reported when aPDT as an adjunct to SRP was compared to SRP alone in the treatment of AgP in one study. One study showed comparable outcomes when aPDT was compared to SRP in the treatment of AgP. In two studies, adjunctive antibiotic administration to SRP showed significantly better outcomes when compared to application of adjunctive use of aPDT to SRP.ConclusionaPDT is effective as an adjunct to SRP for the management of AgP, however, further randomized clinical trials with well defined control groups are needed in this regard.