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.

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.

Long-term follow-up results of a pilot study for nodular basal cell carcinoma with PDT using partial home treatment protocol.

SIGNIFICANCE: Evaluate a photodynamic therapy (PDT) protocol for low-risk basal cell carcinoma (BCC) treatment that requires less time spent at the hospital and is less painful. APPROACH: Eight BCCs were selected, debulked, and received 20 % methyl aminolevulinate cream. After 3 h, the first irradiation was performed at the hospital (20 min, 150 J/cm2). Then, the cream was re-applied, and a portable irradiation prototype was fixed to the skin around the lesion. After 1.5 h, the patients turned on the prototype for irradiation at home (for 2 h, totalizing 312 J/cm2). Disease-free survival rate and pain score during irradiations were evaluated. RESULTS: The clearance at 30 days after PDT was 87.5 % by histological analysis. The mean follow-up was 21.5 months and the recurrence-free survival at 22 months was 75 %. The pain score was significantly lower at home. CONCLUSIONS: A potentially less painful and more comfortable PDT treatment protocol with proven long-term efficiency is presented. A randomized clinical trial has been conducted to confirm these results.

A new photodynamic therapy protocol for nodular basal cell carcinoma treatment: Effectiveness and long-term follow-up.

BACKGROUND: Photodynamic therapy (PDT) has been reported as an excellent option for the treatment of small nodular basal cell carcinomas (nBCC). The standard protocol consists of two sessions, one week apart. Sometimes, returning to the hospital after one week can be impractical for elderly patients, due to comorbidities and mobility issues. Therefore, a new technique performed in one day could be superior for those patients. OBJECTIVE: Evaluate the effectiveness of a PDT Single-visit protocol comparing to the standard protocol, as well as pain and long-term recurrence-free follow-up for nBCC. METHODS: A total of 120 nBCC were treated through a Standard PDT protocol(two sessions, one week apart), and 120 nBCC were treated through a Single-visit PDT(two sessions in one day). A 30-day-after biopsy was performed in order to evaluate the results after the treatment. The lesions that had successful treatment were clinically and dermoscopically evaluated every 6 months up to 60 months. The pain score was compared between the groups(assessed every 3 min during PDT). RESULTS: A complete response at 30-days-after PDT biopsy was observed in 85% of Standard PDT and in 93.3% of Single-visit PDT. Regarding the pain during the illumination, less pain was observed during the second session of the Single-visit PDT. The recurrence-free follow up showed, after 60 months, an 69.0% cumulative probability of recurrence-free for Standard PDT and 80.6% for Single-visit PDT. CONCLUSIONS: The suggested Single-visit PDT protocol resulted in better outcomes at 30-day-after PDT biopsy and in lower recurrence rates than the Standard PDT protocol. A more comfortable and more efficient treatment was offered for the patients, with lower pain.

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.

Field cancerization treatment: Adjustments to an ALA red light photodynamic therapy protocol to improve pain tolerance.

BACKGROUND: Field cancerization (FC) is described as an area with multiple actinic keratosis (AK) in an actinic damaged skin that requires treatment. Photodynamic therapy (PDT) is a treatment option, however, long drug light intervals (DLI) and pain during the illumination remain a challenge OBJECTIVE: Pain and the efficacy of changes in DLI and illumination during PDT treatment for FC were evaluated METHODS: Thirty patients with widespread AK of upper limbs were selected. A 20% aminolevulinic acid (ALA) cream was applied on both forearms and hands after a light curettage. Three groups were evaluated: G1 (3 h of DLI); G2 (1.5 h of DLI); and, G3 (1.5 h of DLI with two-minutes pauses every 10 min during illumination). The limbs were treated with a LED prototype at 630 nm (36 J/cm2 of fluence in 40 min of irradiation). The pain score during illumination was evaluated with a numeric scale (from 0 to 10) and pain was defined as low (0-3), moderate (4-6), and severe (7-10). The AK counting was clinically performed before and 30 days after PDT. Significance between groups was tested using ANOVA single factor. RESULTS: A mean reduction in AK number of 56% in G1, 55% in G2, and 66% in G3 were observed, with no statistical significance. The comparison pain among the groups showed best results for G3 (p < 0,05). CONCLUSION: Using paused illumination and 1.5 h of DLI was possible to improve tolerance maintaining the clearance in red light ALA - PDT treatment.

Physiotherapy elastic band disinfection by UV-C irradiation in an intensive care unit.

BACKGROUND: The transmission of healthcare-associated pathogens is mainly related to the massive flow of patients with infections in hospitals, presenting surfaces as potential transmission sources of these microorganisms. The physiotherapist who works in the intensive care area has become a specialist in daily routine in critical care with ventilatory support and post-surgical recovery. Furthermore, for this, the instruments are used in the patient's hands and body. Chemicals such as chlorine derivatives, triclosan, chlorhexidine and, 70 % alcohol are currently used to decontaminate surfaces. This study evaluated ultraviolet C (UV-C) irradiation efficiency in the physiotherapy object's disinfection in daily use in the Hospital Intensive Care Unit (ICU). METHODS: the microbiological quantification carried out using the elastic band during physiotherapy in a cross-sectional study with 21 patients. The methodology compared the cleaning protocol (70 % alcohol) with a new irradiation method in elastic band in the ICU. RESULTS: The results showed microbial reductions in the elastic band using both 70 % alcohol and UV-C irradiation (254 nm), with 60 s of illumination, totaling a light dose of 0.78 J/cm2; however, the UV-C irradiation showed better results. CONCLUSION: This study showed that disinfection by UV-C irradiation could be introduced in an intensive care hospital environment for physiotherapeutic conduct.

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.

Dual-Agent Photodynamic Therapy with Optical Clearing Eradicates Pigmented Melanoma in Preclinical Tumor Models.

Treatment using light-activated photosensitizers (photodynamic therapy, PDT) has shown limited efficacy in pigmented melanoma, mainly due to the poor penetration of light in this tissue. Here, an optical clearing agent (OCA) was applied topically to a cutaneous melanoma model in mice shortly before PDT to increase the effective treatment depth by reducing the light scattering. This was used together with cellular and vascular-PDT, or a combination of both. The effect on tumor growth was measured by longitudinal ultrasound/photoacoustic imaging in vivo and by immunohistology after sacrifice. In a separate dorsal window chamber tumor model, angiographic optical coherence tomography (OCT) generated 3D tissue microvascular images, enabling direct in vivo assessment of treatment response. The optical clearing had minimal therapeutic effect on the in control, non-pigmented cutaneous melanomas but a statistically significant effect (p < 0.05) in pigmented lesions for both single- and dual-photosensitizer treatment regimes. The latter enabled full-depth eradication of tumor tissue, demonstrated by the absence of S100 and Ki67 immunostaining. These studies are the first to demonstrate complete melanoma response to PDT in an immunocompromised model in vivo, with quantitative assessment of tumor volume and thickness, confirmed by (immuno) histological analyses, and with non-pigmented melanomas used as controls to clarify the critical role of melanin in the PDT response. The results indicate the potential of OCA-enhanced PDT for the treatment of pigmented lesions, including melanoma.

Multispectral autofluorescence dermoscope for skin lesion assessment.

Basal cell carcinoma (BCC) is the most common type of skin cancer. Diagnosis and edge assessment of BCC lesions are based on clinical and dermoscopy evaluation, which are strongly dependent on the expertise and training of the physician. There is a high rate of underdiagnosis because BCC is frequently confused with certain common benign lesions and is often indistinguishable from the surrounding healthy tissue. In the present study, a multispectral fluorescence lifetime imaging (FLIm) dermoscopy system, designed for imaging and analyzing the autofluorescence emission of skin tissue, was used to image thirty-eight patients with diagnosed nodular BCC (nBCC) lesions, using clinically acceptable levels of excitation light exposure. With this system, skin autofluorescence was imaged simultaneously using three emission bands: 390 ±â€¯20 nm, 452 ±â€¯22 nm, and >496 nm, preferentially targeting collagen, NADH, and FAD autofluorescence, respectively. Statistical classifiers based on FLIm features developed to discriminate BCC from healthy tissue showed promising performance (ROC area-under-the-curve of 0.82). This study demonstrates the feasibility of clinically performing multispectral endogenous FLIm dermoscopy providing baseline results indicating the potential of this technology as an image-guided tool to improve the delineation of nBCC during surgical lesion resection.

Field cancerization treatment using topical photodynamic therapy: A comparison between two aminolevulinate derivatives.

The objective of this study was to evaluate and compare the clinical response to PDT (Photodynamic Therapy) in field cancerization using two aminolevulinate derivatives. Forty patients with multiple actinic keratosis (AK) on forearms and hands scattered received two sessions of ALA and MAL-PDT at 630 nm (36 J/cm2). The AK clearance rate was 72 % for both drugs with a significant decrease in AK observed clinically (p < 00,001). Clinical improvement in field cancerization using two aminolevulinate derivatives in PDT is proven with no significant difference in the efficacy of drugs.

Use of dermograph for improvement of PpIX precursor's delivery in photodynamic therapy: Experimental and clinical pilot studies.

BACKGROUND: Photodynamic Therapy (PDT) is a treatment for non-melanoma skin cancer. One of the main challenges of topical PDT is to increase the precursor penetration when applied on the lesion. Protoporphyrin IX (PpIX) is an endogenous photosensitizer (PS) widely used, obtained by the administration of precursors such as aminolevulinic acid and methyl aminolevulinate. Aiming for the technique improvement by providing greater PS penetration in skin lesions, we tested a new approach for drug delivery with a minimally invasive technique. A dermograph is a device currently used in aesthetic procedures to promote skin rejuvenation or to micropigmentation. The use of dermograph for drug delivery has not been particularly explored for PDT so far, and the present study explores that approach as its main goal. METHODS: This study evaluated the PpIX distribution and PDT damage in normal rat skin model; the response of dermograph application in a pilot clinical study was also investigated. RESULTS: The animal tests showed that more homogeneous PpIX distribution and greater penetration in the tissue was observed with dermograph when compared to the topical application. Six nodular basal cell carcinoma lesions were treated with PDT using intradermal delivery by dermograph, and no recurrence was observed after 28 months of follow-up. CONCLUSIONS: The precursor's penetration improvement and the consequent increase in PpIX distribution in-depth both favor PDT response, providing upgrades concerning problems that hinder the clinical practice acceptance.

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.

Single visit PDT for basal cell carcinoma - A new therapeutic protocol.

Non-melanoma skin cancer is the most prevalent type of cancer in Brazil and worldwide. Topical Photodynamic Therapy is a technique that offers advantages as: excellent aesthetic result, possibility of application for outpatients in ambulatory setting, and presenting a minimum functional impact of the treated anatomic site. Fractionated Photodynamic Therapy is a modification of the usual technique in which the full dose of light is delivered in steps separated by a periods of time ("dark intervals"). In Brazil, no studies using this technique for treatment of BCC have been published. Thus, we proposed to evaluate the complete and partial response to the four different protocols of fractional Photodynamic Therapy, when evaluated 30 days after treatment. The study showed a complete response of 65.8%, 67.6%, 72.7% and 95.4% in the groups 1, 2, 3 and 4, respectively. We observed that the dark interval and the irradiated light dose are parameters of great importance for the final response to the treatment. Our results suggest that Fractionated Photodynamic Therapy is a technique with excellent aesthetic result and complete response when evaluated 30 days after treatment. However, a longer follow-up will be necessary for better understanding of the behavior of the lesions treated.

Portable fluorescence lifetime spectroscopy system for in-situ interrogation of biological tissues.

Fluorescence spectroscopy and lifetime techniques are potential methods for optical diagnosis and characterization of biological tissues with an in-situ, fast, and noninvasive interrogation. Several diseases may be diagnosed due to differences in the fluorescence spectra of targeted fluorophores, when, these spectra are similar, considering steady-state fluorescence, others may be detected by monitoring their fluorescence lifetime. Despite this complementarity, most of the current fluorescence lifetime systems are not robust and portable, and not being feasible for clinical applications. We describe the assembly of a fluorescence lifetime spectroscopy system in a suitcase, its characterization, and validation with clinical measurements of skin lesions. The assembled system is all encased and robust, maintaining its mechanical, electrical, and optical stability during transportation, and is feasible for clinical measurements. The instrument response function measured was about 300 ps, and the system is properly calibrated. At the clinical study, the system showed to be reliable, and the achieved spectroscopy results support its potential use as an auxiliary tool for skin diagnostics.

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

BACKGROUND: Topical 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. METHODS: Fluorescence measurements were used to investigate the build up of PpIX within the tumour tissue during the 3h 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. RESULTS: It 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. CONCLUSIONS: The study extends and supports previous knowledge of PpIX production during the occlusive treatment phase.

Laptop computer induced erythema ab igne: a new presentation of an old disease.

Erythema ab igne is a condition characterized by skin changes due to chronic exposure to moderate temperature. We describe a female patient with continuous use of a laptop computer on exposed legs for 6 months and consequent development of reticulated hyperpigmentation at the area. Histopathological examination revealed epidermal atrophy, collagen fragmentation, and vacuolar changes in the basal layer, among other signs. We consider this case to be a modern cause of erythema ab igne.

Oral chronic graft-versus-host disease: analysis of dendritic cells subpopulations.

The graft-versus-host disease is the major cause of morbidity and mortality in patients who have undergone hematopoietic stem cell transplantation. Aiming at contributing to the understanding of the role of myeloid and plasmacytoid dendritic cells, and natural killer cells in chronic graft-versus-host disease, we examined biopsies of jugal mucosa of 26 patients with acute myeloid leukemia who had undergone allogenic hematopoietic stem cell transplantation. Half of these patients developed oral chronic graft-versus-host disease. Microscopic sections were immunohistochemically stained for anti-CD1a, anti-CD123 and anti-CD56. We calculated the number of immunostained cells in the corium per square millimeter and applied the Mann-Whitney test. Results showed a statistically significant increase of myeloid dendritic cells (CD1a+; p=0,02) and natural killer cells (CD56; p=0,04) in patients with oral chronic graft-versus-host disease. CD123 immunostaining showed no statistical difference between groups. It was concluded that myeloid dendritic cells and natural killer cells participate in the development of oral chronic graft-versus-host disease.

Chronic graft-versus-host disease: clinical presentation of multiple lesions of lichenoid and atrophic pattern.

Graft-versus-host disease is observed mainly in recipients of hematopoietic cell transplantation and is expressed by cutaneous or systemic signals and symptoms. Graft-versus-host disease is clinically classified as acute or chronic. Chronic Graft-versus-host disease occurs in up to 70% of hematopoietic cell transplanted patients and its clinical manifestations have important impact on morbidity and quality of life. The authors report an expressive cutaneous, oral and adnexal involvement in a patient with chronic Graft-versus-host disease with multiple lesions of lichenoid and atrophic pattern.