Photodynamic therapy for nodular basal cell carcinoma up to 5mm located on high-risk area: Effectiveness and long-term follow-up results.

SIGNIFICANCE: Response rates evaluation of photodynamic therapy (PDT) for nodular basal cell carcinoma (BCC) treatment located on high-risk and low-risk areas of the face. APPROACH: Two groups of nodular BCC were selected, debulked, and received 20% methyl aminolevulinate (MAL) hydrochloride cream. After 3 h, the first irradiation was performed (20 min, 150 J/cm2). Then, the cream was re-applied, and a second irradiation was performed after 1.5 h (20 min, 150 J/cm2). Clearance at 30 days and recurrence-free survival rate were evaluated. RESULTS: The clearance at 30 days after PDT was 89% for the low-risk area group and 87% for the high-risk group. The recurrence-free survival at 60 months was 82% and 85% for the high-risk and low-risk groups, respectively. CONCLUSIONS: No significant differences were observed between groups nor for clearance at 30 days, nor recurrence-free follow-up. These results make PDT possible option for nodular BCC less than 5 mm located in high-risk areas.

Ultrasonic scalpel associated with photodynamic therapy in the treatment of refractory vulvar condyloma acuminatum.

This is a case report of a patient with vulvar condyloma acuminatum associated with hyperkeratosis and folliculitis, which had been refractory to two previous therapies. The patient had been successfully treated using a combination of promising techniques: the ultrasonic scalpel and MAL photodynamic therapy.

Fast Fabrication of Multifunctional PCL/Curcumin Nanofibrous Membranes for Wound Dressings.

Therapeutic intervention to skin wounds requires covering the affected area with wound dressings. Interdisciplinary efforts have focused on the development of smart bandages that can perform multiple functions. In this direction, here, we designed a low cost (U$0.012 per cm2) multifunctional therapeutic wound dressing fabricated by loading curcumin (CC) into poly(ϵ-caprolactone) (PCL) nanofibers using solution blow spinning (SBS). The freestanding PCL/CC bandages were characterized by distinct physicochemical approaches and were successful in performing varied functions, including controlled release of CC, colorimetric indication of the wound conditions, barrier against microorganisms, being biocompatible, and providing a photosensitive platform for antimicrobial photodynamic therapy (aPDT). The chemical nature of PCL and CC and the interactions between these components allowed CC to be released for 192 h (ca. 8 days), which could be correlated with the Korsmeyer-Peppas model, with a burst release suitable to treat the inflammatory phase. Due to the CC keto-enol tautomerism, an optical indication of the healing status could be obtained using PCL/CC, which occurred immediately, ranging between red/orange and yellow shades. The effect against pathogenic microorganisms evaluated by agar disc-diffusion, affected skin wound simulation (ex vivo), and microbial penetration tests demonstrated the ability to block and inhibit microbial permeation in different environments. The biocompatibilities of PCL and PCL/CC were verified by in vitro cytotoxicity study, which demonstrated that cell viabilities average above 94 and 96% for human dermal fibroblasts. In addition, the proposed bandage responded to aPDT applied to an in vivo assay, showing that, when irritated, PCL/CC was able to reduce the bacteria present on the real wound of mice. In summary, our findings demonstrate that using PCL and CC to produce nonwovens by the SBS technique offers potential for the rapid fabrication of biocompatible and multifunctional wound dressings, paving the way for large-scale production and utilization of such dressings in the treatment of skin wounds.

HPV-induced condylomata acuminata treated by Photodynamic Therapy in comparison with trichloroacetic acid: A randomized clinical trial.

OBJECTIVES: This is a randomized controlled clinical trial comparing Photodynamic Therapy (PDT) and the application of trichloracetic acid (TAA) in the treatment of HPV condyloma in the perianal and vulva regions. Design, Randomised controlled, open label, trial. They were allocated to each treatment following randomization by a computer program. SETTING: Women Health Ambulatory in São Carlos city, São Paulo State in the Brazil. PARTICIPANTS: 36 patients evaluated. 31 patients fulfilled the study requirements. INTERVENTION: Photodynamic Therapy (PDT) versus trichloracetic acid (TAA). The PDT protocol used the prodrug methyl aminolevulinate incubated for 3 hours and irradiation at 630 nm (100 J/cm²). In the treatment using TAA, warts received a small amount of acid using a cotton swab. Both treatments were repeated weekly until the lesions disappeared completely or until 10 sessions were completed. MAIN OUTCOME MEASURE: Clinical analysis. Follow-up between 12 and 30 months after the complete treatment. RESULTS: A total of 16 patients were treated with PDT and 15 patients with TAA. A complete response rate of 60% for TAA and 63% for PDT, with a recurrence rate of 33% for TAA and 0% for PDT. CONCLUSION: PDT appears not only to treat lesions due to physical destruction of condyloma and subclinical lesions, but also to modulate the immune system and/or also to decrease the local viral load, suggesting a lower recurrence compared to the TAA group.

One-Pot Microwave-Assisted Synthesis of Carbon Dots and in vivo and in vitro Antimicrobial Photodynamic Applications.

Carbon-based photosensitizers are more attractive than the other ones based on their low cost, high stability, broadband of light absorption, tunable emission spectra, high quantum yield, water solubility, high resistance to metabolic degradation, and selective delivery. These properties allow multiple applications in the field of biology and medicine. The present study evaluated in vitro and in vivo the antimicrobial photodynamic effect of a one-pot microwave produced C-DOTS based on citric acid. The in vitro assays assessed the effectiveness of illuminated C-DOTS (C-DOTS + light) against Staphylococcus aureus suspension and biofilm. The concentrations of 6.9 and 13.8 mg/mL of C-DOTS and light doses of 20 and 40 J/cm2 were able to reduce significantly the microorganisms. Based on these parameters and results, the in vivo experiments were conducted in mice, evaluating this treatment on wounds contaminated with S. aureus. The viability test showed that C-DOTS-mediated photodynamic inactivation reduced 104 log of the bacteria present on the skin lesions. These results, altogether, showed that antibacterial photodynamic therapy using C-DOTS is a promising and viable treatment for Gram-positive bacteria-infected wounds.

Photodynamic therapy as a treatment option for multiple pigmented basal cell carcinoma: Long-term follow-up results.

Photodynamic therapy (PDT) has been used worldwide as a non-surgical option for the treatment of basal cell carcinoma (BCC). PDT treatment for pigmented BCC is not frequently performed because of poorer results, which are explained by lower penetration of the light, possibly related to the melanin absorption in the visible range wavelengths. However, there is evidence for an increase in PDT cure rates with prior debulking of the lesion. In this study, we reported a complete clearance of 30 pigmented basal cell carcinomas in 2 patients. PDT was performed in a single visit protocol, which consists of two illumination sessions performed on the same day (125 mW/cm² of irradiance and 150 J/cm² of fluence). Imediately after the debulking of the BCC, a 20 % methyl aminolevulinate cream was applied and occluded for 3 h in the first session and 1.5 h in the second. After 30 days of the treatment, all regions were evaluated clinically and histologically, showing no residual BCC. Even with long-term follow-up (mean of 24 months), no recurrence was detected.. This PDT protocol achieved 100 % control for pigmented BCC. Therefore, it was demonstrated that PDT may be a successful treatment option for small and multiple pigmented BCC.

MAL-associated methyl nicotinate for topical PDT improvement.

Photosensitization of all tissue in sufficient quantity to generate damage is one of the limiting factors for Photodynamic Therapy (PDT) efficiency. Methyl nicotinate (MN) is a thermogenic and vasodilating substance that facilitates the topical tissue penetration of some compounds. The topical MAL (methyl aminolevulinate) PDT is commonly used as a precursor of protoporphyrin IX (PpIX). This study investigates the safety of topical use in NM, as well as its ability to improve the efficiency of topical PDT. For this, we investigate the cytotoxicity of MN, as well as its actions in increasing cellular metabolism and vasodilation. Besides, its ability to optimize the formation of PpIX in the tissue when associated with MAL cream was investigated, besides assessing the severity of necrosis obtained by treatments. The cytotoxicity of MN was tested for concentrations of 0, 0.1, 0.25, 0.5, 0.75 and 1% in cell culture. For the concentration of 0.5%, the cellular metabolism was evaluated using confocal microscopy to calculate the redox rate. In the Chorioallantoic Membrane Model, vasodilation was evaluated for concentrations of 0.5 and 1% MN during 1 h of incubation. In the animal model, the healthy skin of Wistar rat was used to evaluate the production of PpIX in the tissue and the degree of necrosis obtained by Photodynamic therapy when using NM associated with methyl aminolevulinate. It was observed the non-cytotoxicity in vitro of MN in the concentration used (0.5%) and its ability to increase cellular metabolism. In a chorioallantoic model, the MN vasodilation power was demonstrated for different caliber of vessels. In vivo studies are showing that the incorporation of MN in the MAL cream increases the amount of PpIX produced in the tissue causing a higher effect on the epidermis after PDT. This improvement of the protocol may make the procedure more effective both in the destruction of tumor tissue and in the treatment of deeper cells decreasing possible recurrence, in addition to allowing improvements in the protocol, such as reducing the cream's incubation time.

High-risk HPV clearance and CIN 3 treated with MAL-PDT: A case report.

High-grade cervical intraepithelial neoplasia (CIN) is the precursor to cervical cancer. HPV (human papillomavirus) infection is strongly related with this disease. The CIN treatment is generally excision of the transformation zone (ETZ). Photodynamic therapy (PDT) has also shown to be a promising treatment. We are reporting a case of a 33-years-old patient with high-grade CIN 3 treated with topical MAL (methyl aminolevulinate) PDT. Was applied 2.5 g of 20 % (w/w) MAL cream overnight and the cervix was illuminated twice, with three weeks apart, using a probe with LEDs simultaneously with a cylindrical laser fiber emitting both at 630 nm, with a fluency of 150 J/cm2. CIN 3 and the presence of high-risk HPV virus was eliminated 120 days after the second procedure. There was no recurrence at 6 months follow-up. This case report using MAL-PDT and a different light arrangement with LEDs and laser fiber associated both cured the patient with CIN 3 and eliminated low and high-risk HPV in just two PDT sessions.

HPV condylomatosis region treated with multiple sessions of MAL-PDT: A case report.

Condyloma or genital warts affect the tissues of the genital area due to infections induced by Human papillomavirus. There are some topical therapies indicated for condyloma lesions treatment but all of them present a high rate of recurrence. Photodynamic Therapy is proving to be an interesting strategy for treating these lesions, capable also to treat virus-infected cells on subclinical lesions. A patient with a significative condylomatosis region was treated with six MAL-PDT sessions. Due to its large thickness, other topical procedures probably would have low effectiveness. After the treatment, the tissue presented clinical absence of lesion and no apparent scar, with good aesthetic result and preserving the sensitivity of the region and a follow up of eleven months without recurrence.

Temperature effect on the PpIX production during the use of topical precursors.

Decreasing incubation time, as well as enhanced PpIX production, are present challenges for topical photodynamic therapy (PDT). There are reports concerning the existence of a strong relationship between site temperature and porphyrin synthesis in biological tissue, that suggest temperature increase in the tissue can improve the formation of PpIX. The main objective of this study is to determine whether the temperature change of the tissue favors the production of PpIX. Creams containing aminolevulinic acid (ALA) and methyl aminolevulinate (MAL) were topically administered for 30 min on healthy skin of rats' back and the formation of PpIX was evaluated for 180 min. The animals were divided into 5 groups: cooling tissue to 20 °C or heating tissue to 40 °C (either before or after incubation of the cream) and control group (unchanged temperature). The tissue temperature was evaluated by thermography. The influence of temperature was evaluated both concerning cream penetration and the production of PpIX. It was found that both ALA and MAL led to an increase of about 20% PpIX production when the tissue was warmed before incubation of the cream, suggesting that the penetration improved. When the thermal change was promoted after incubation of the cream, the production of PpIX decreased both by heating and cooling, probably related to enzyme modification. The results found in this study suggest that the increase of tissue temperature before the cream incubation can improve the clinical protocols of topical PDT using ALA or MAL, improving the efficiency of the procedure by increasing the production of PpIX and allowing the decrease of the incubation period.

Photodynamic therapy in combination with surgery for the treatment of an extensive squamous cell carcinoma in situ - A case report.

The combination of multiple sessions of Photodynamic therapy (PDT) and surgery have been used to treat an extensive superficial lesion of squamous cell carcinoma in situ. Methyl aminolevulinate (MAL) mediated PDT was applied to reduce the tumoral area and a small surgical removal was performed to complete elimination of the lesion. The reduction of the tumor area avoided the need for a skin graft application as well as possible postoperative complications, offering a more favorable cosmetic outcome. Two-years of follow-up showed no recurrence. The case is interesting and demonstrate potentialities for the combined use of PDT and surgery.

Energy analysis of PDT using thermography during the treatment of basal cell carcinoma.

The changes in tissue temperature of basal cell carcinoma lesions were investigated during photodynamic therapy in order to better understand the effects and mechanisms of PDT in tissue. In this study, the monitoring of 40 lesions of basal cell carcinoma was performed during photodynamic therapy. The lesion region becomes thermally evident throughout the procedure, and there is an improved contrast of the lesion edges after the end of the irradiation. The comparison between thermal and fluorescence images showed a correlation between the PpIX evidenced through widefield fluorescence and the temperature gradient of the thermal images after the procedure, indicating that thermography is a potential diagnostic tool to evaluate the selective response of PDT. A model was created to calculate the amount of light energy converted to heat, tissue damage, and other energy transfer processes involved in the PDT. Using this model, it was shown that most of the energy conversion was in photodynamic action (48.7% and 48.3%, in first and second session, respectively), followed by the energy ratio attributable to blood perfusion (37.2%). This is evidence that photodynamic therapy does not generate a significant thermal component, an important aspect of the study of its mechanisms.

Overall Results for a National Program of Photodynamic Therapy for Basal Cell Carcinoma: A Multicenter Clinical Study to Bring New Techniques to Social Health Care.

Along the past years, a national program to implement photodynamic therapy (PDT) for nonmelanoma skin cancer (NMSC) was performed over the Brazilian territory. Using a strategy involving companies, national bank, and medical partners, equipment, medication, and protocols were tested in a multicenter study. With results collected over 6 years, we could reach a great deal of advances concerning the use of PDT for skin cancer. We present the overall reached results of the program and discuss several aspects about it, including public politics of treatment. A discussion about advantages of this technique within conditions of health care is placed, comparing PDT with surgery, including an analysis about the implementation of PDT in countries in development as Brazil, considering not only technical but social aspects, as the distribution of medical doctor in the Brazilian territory. The program resulted in a huge dissemination of PDT in Brazil and many countries in Latin America, in a partnership among public politics, universities, companies, and hospitals and clinics and in the insertion of national technologies as option to treat NMSC. Consequence of the program is mainly the continuation of the use of PDT in Brazil and many countries in Latin America.