José Dirceu Vollet Filho

Experience and BCC subtypes as determinants of MAL-PDT response: Preliminary results of a national Brazilian project

Non-melanoma skin cancer is the most prevalent cancer type in Brazil and worldwide. Photodynamic therapy (PDT) is a noninvasive technique with excellent cosmetic outcome and good curative results, when used for the initial stages of skin cancer. A Brazilian program was established to determine the efficacy of methyl aminolevulinate (MAL)-PDT, using Brazilian device and drug. The equipment is a dual device that combines the photodiagnosis, based on widefield fluorescence, and the treatment at 630nm. A protocol was defined for the treatment of basal cell carcinoma with 20% MAL cream application. The program also involves the training of the medical teams at different Brazilian regions, and with distinct facilities and previous PDT education. In this report we present the partial results of 27 centers with 366 treated BCC lesions in 294 patients. A complete response (CR) was observed in 76.5% (280/366). The better response was observed for superficial BCC, with CR 160 lesions (80.4%), when compared with nodular or pigmented BCC. Experienced centers presented CR of 85.8% and 90.6% for superficial and nodular BCC respectively. A high influence of the previous doctor experience on the CR values was observed, especially due to a better tumor selection.

Photodynamic therapy: Progress toward a scientific and clinical network in Latin America.

Cancer is one of the major challenges for Latin America health services, since the skin cancer is the most frequent lesion. This manuscript addresses an initiative for the treatment of basal cell carcinomas (BCC) by photodynamic therapy (PDT) based on a government-funded national program in Brazil. The program provides clinical training and facilitates access to drugs/equipment and significantly reduces PDT costs. It also lays foundations for the establishment of a Latin American research network to improve prevention, early detection and treatment of diseases. Centers have been established by direct contact (conferences, visits to healthcare facilities and official departments). A local training was divided into complementary theoretical and practical parts. This is an ongoing project that has involved 10 countries: Brazil, Bolivia Chile, Ecuador, El Salvador, Colombia, Cuba, Mexico, Peru and Venezuela, The initial results are encouraging and have provided assessment of Latin America patients relating, for example, the most common skin phototypes with incidence of BCC in such countries. The network is expected to produce relevant scientific information for PDT introduction in many countries. The experience acquired by local teams shall enable them to innovate PDT protocols and increase the number of skilled contributors/researchers to broaden knowledge on the ever-crescent PDT field in Latin America. The establishment of a collaboration network and introduction of other projects and experience exchange shall become an easier process with time. This PDT clinical research network is a start for the strengthening of Science in South Hemisphere countries.

Interstitial PDT using diffuser fiber—investigation in phantom and in vivo models

Photodynamic therapy (PDT) has been used for local treatment of several types of tumors. Light penetration of biological tissue is one limiting factor in PDT, decreasing the success rates of the treatment of invasive and solid tumors. In those cases, a possible solution is to use interstitial PDT, in which both diffuser optical fibers are inserted into the tumor. The uniformity of the diffuser emission plays a crucial role in planning the delivery of the appropriate light fluence and in ensuring treatment success. In this study, we characterized a diffuser optical fiber concerning its homogeneity. We showed that the diffuser emission can be inhomogeneous and that the necrosis generated by interstitial PDT using such a diffuser for illumination is asymmetrical in volume as a result. This observation has relevant consequences in achieving success in PDT and phototherapies in general, as the delivered light fluence depends on adequate previous knowledge of the irradiation profile.

Evaluation of PpIX formation in Cervical Intraepithelial Neoplasia I (CIN) using widefield fluorescence images

Optical techniques has been described as auxiliary technology for screening of neoplasia because shows the potential for tissues differentiation in real-time and it is a noninvasive detection and safe. However, only endogenous fluorophores presents the lesion may be insufficient and needed of the administration of the fluorophores synthesized, such as, precursor molecule of protoporphyrin IX (PpIX) induced by 5- aminolevulinic acid and your derivatives. Topical application of methylaminolevulinate (MAL), induces formation of the endogenous photosensitizer, PpIX in tissues where carcinogenesis has begun. The PpIX tend to accumulate in premalignant and malignant tissues and the illumination with light with appropriate wavelength beginning to excitation of PpIX fluorescence, which helps to localize PpIX-rich areas and identify potentially malignant tissues. The aim of the study is to evaluate the production of PpIX in the cervix with CIN I through of the fluorescence images captured after 1 hour of cream application. It was possible to visualize PpIX fluorescence in cervix and it was possible to observe the selectivity in fluorescence in squamous-columnar junction, which a pre-cancerous condition (CIN) and usually is localized. Through the image processing it was possible to quantify the increase of red fluorescence. For the CIN I the increase of red fluorescence was approximately of 4 times indicating a good PpIX formation.

Effect of irradiation with different laser wavelengths on oxidative stress of non-hepatectomized rats

PURPOSE To assess the effect of two laser wavelengths, either separate or combined, on intact rat livers. METHOD Nineteen male Wistar rats (200-300 g) were submitted to laser irradiation at 5 different sites on the liver surface.Wavelengths 660 and 780 nm were used, with a dose of irradiation of 60 J/cm2/site.The animals were divided into the groups:control (C) and animals irradiated with 660 nm laser (L1), with 780 nm laser (L2) or withboth wavelengths (L3).Mitochondrial function, mitochondrial swelling, and hepatocellular malondialdehyde (MDA) levels were determined.Data were analyzed by the Mann-Whitney test, with the level of significance set at 5%. RESULTS There was a reduction of ADP-activated respiration (state 3) in group L1 compared to group C (p=0.0016), whereas the values of group L2 were similar to control.Group L3 also showed a reduction of state 3 (p=0.0159).There was a reduction of RCR in group L1 compared to control (p=0.0001) and to group L2 (p=0.0040).Mitochondrial swelling only differed between group L3 and control (p=0.0286).There was a increase in MDA levels in group L3 compared to control (p=0.0476) and to group L2 (p=0.0286) and in group L1 compared to group L2 (p=0.0132). CONCLUSION Although laser irradiation reduced mitochondrial function,it did not interfere with the hepatocellular energy status.

The relevance of light diffusion profiles for interstitial PDT using light-diffusing optical fibers

Photodynamic therapy (PDT) is a technique used for several tumor types treatment. Light penetration on biological tissue is one limiting factor for PDT applied to large tumors. An alternative is using interstitial PDT, in which optical fibers are inserted into tumors. Cylindrical diffusers have been used in interstitial PDT. Light emission of different diffusers depends on the manufacturing process, size and optical properties of fibers, which make difficult to establish an adequate light dosimetry, since usually light profile is not designed for direct tissue-fiber contact. This study discusses the relevance of light distribution by a cylindrical diffuser into a turbid lipid emulsion solution, and how parts of a single diffuser contribute to illumination. A 2 cm-long cylindrical diffuser optical fiber was connected to a diode laser (630 nm), and the light spatial distribution was measured by scanning the solution with a collection probe. From the light field profile generated by a 1 mm-long intermediary element of a 20 mm-long cylindrical diffuser, recovery of light distribution for the entire diffuser was obtained. PDT was performed in rat healthy liver for a real treatment outcome analysis. By using computational tools, a typical necrosis profile generated by the irradiation with such a diffuser fiber was reconstructed. The results showed that it was possible predicting theoretically the shape of a necrosis profile in a healthy, homogeneous tissue with reasonable accuracy. The ability to predict the necrosis profile obtained from an interstitial illumination by optical diffusers has the potential improve light dosimetry for interstitial PDT.

PDT and emerging therapies for Actinic Keratosis—A resource letter

Aktinic Keratosis is common and if left untreated may develop into life threatening squamous cell carcinoma. Therefore early intervention is the standard of care. While many treatments are available PDT continues to move to the for - front for this indication (Brito et al., 2016 [31]). Topical PS is commercially available that are able to reliably ablate these lesions. Innovative protocols including sunlight, large volume LED arrays and maneuvers to improve treatment parameters and cosmesis continue to make this a worldwide treatment of choice for AK.

Monitoring of Ehrlich tumor growth using thermal image

In this study, we injected Ehrlich tumor cell in the dorsal region of nine Swiss mouse. The tumor in growth was assessed using thermography to monitor temperature changes and to observe the minimal tumor size that can be detected.

Evaluation of the Necrosis Profile Induced by ALA-PDT with the Association of Tissue Micromachining Using Femtosecond Laser Ablation

Abstract: The aim of this study was the investigation of the 5-aminolevulinic acid (a tissue precursor for protoporphyrin-IX) penetration in rats’ liver after tissue micromachining obtained by femtosecond laser ablation.