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.

Topical and intradermal delivery of PpIX precursors for photodynamic therapy with intense pulsed light on porcine skin model.

In order to purposely decrease the time of the photodynamic therapy (PDT) sessions, this study evaluated the effects of PDT using topical and intradermal delivery of two protoporphyrin (PpIX) precursors with intense pulsed light (IPL) as irradiation source. This study was performed on porcine skin model, using an IPL commercial device (Intense Pulse Light, HKS801). IPL effect on different administration methods of two PpIX precursors (ALA and MAL) was investigated: a topical cream application and an intradermal application using a needle-free, high-pressure injection system. Fluorescence investigation showed that PpIX distribution by needle-free injection was more homogeneous than that by cream, suggesting that a shorter drug-light interval in PDT protocols is possible. The damage induced by IPL-PDT assessed by histological analysis mostly shows modifications in collagens fibers and inflammation signals, both expected for PDT. This study suggested an alternative protocol for the PDT treatment, possibility half of the incubation time and with just 3 min of irradiation, making the IPL-PDT, even more, promising for the clinical treatment.

Photodynamic therapy for the treatment of induced mammary tumor in rats.

The objective of this work was to evaluate photodynamic therapy (PDT) by using a hematoporphyrin derivative as a photosensitizer and light-emitting diodes (LEDs) as light source in induced mammary tumors of Sprague-Dawley (SD) rats. Twenty SD rats with mammary tumors induced by DMBA were used. Animals were divided into four groups: control (G1), PDT only (G2), surgical removal of tumor (G3), and submitted to PDT immediately after surgical removal of tumor (G4). Tumors were measured over 6 weeks. Lesions and surgical were LEDs lighted up (200 J/cm(2) dose). The light distribution in vivo study used two additional animals without mammary tumors. In the control group, the average growth of tumor diameter was approximately 0.40 cm/week. While for PDT group, a growth of less than 0.15 cm/week was observed, suggesting significant delay in tumor growth. Therefore, only partial irradiation of the tumors occurred with a reduction in development, but without elimination. Animals in G4 had no tumor recurrence during the 12 weeks, after chemical induction, when compared with G3 animals that showed 60 % recurrence rate after 12 weeks of chemical induction. PDT used in the experimental model of mammary tumor as a single therapy was effective in reducing tumor development, so the surgery associated with PDT is a safe and efficient destruction of residual tumor, preventing recurrence of the tumor.

Study of laser fluorescence spectroscopy in livers of rats with hypothermic ischemia.

PURPOSE: After partial hepatectomy (PH), the remaining liver (RL) undergoes regenerative response proportional to the host. Limited literature exists on hepatic viability after tissue injury during hypothermic preservation. Spectroscopy measures cellular fluorescence and is explored for tissue characterization and parameter investigation. This study aimed to assess fluorescence analysis (spectroscopy) in evaluating liver viability and its relationship with hepatic tissue regeneration 24 hours after PH. Additionally, we analyzed liver regeneration in RL after 70% partial hepatectomy under hypothermic conditions with laser irradiation. METHODS: Fifty-six Wistar rats were divided into four groups: total non-perfused liver (control), total perfused liver, partial hepatectomy "in situ", and partial hepatectomy "ex situ". Tissue analysis was performed at 0 and 24 hours using spectroscopy with laser devices emitting at 532 (green) and 405 nm (violet). RESULTS: Spectroscopy identified tissue viability based on consistent results with Ki67 staining. The fluorescence spectra and Ki67 analysis displayed similar patterns, linking proliferative activity and absorption intensity. CONCLUSIONS: Fluorescence spectroscopy proves to be promising for real-time analysis of cellular activity and viability. Metabolic activity was observed in groups of live animals and hypothermically preserved samples, indicating cellular function even under blood deprivation and hypothermic conditions.

Fluorescence spectroscopy for clinical transplantation liver grafts monitoring: possibilities offered by 408 nm excitation.

PURPOSE: Fluorescence spectroscopy techniques have been investigated aiming to reduce the invasiveness of methods for investigation of tissue. In transplantation procedures, it may offer the possibility of a complementary technique for the monitoring of liver grafts' conditions prior to and during the transplantation procedure stages involving cold perfusion. The objective of this study was to evaluate fluorescence spectroscopy under violet light excitation (408 nm) for the monitoring of clinical hypothermic liver transplantation procedures. METHODS: Organ grafts were monitored from before the removal of the donor's body to 1 h after the implant into the receptor's body. Fluorescence spectroscopy was assessed over five stages within these transplant stages. RESULTS: The study provided evidence of a correlation between fluorescence information collected during liver grafts transplantation and the survival of patients. CONCLUSIONS: Fluorescence spectroscopy can become a tool to monitor transplantation grafts, providing objective information for the final decision of surgeons to use organs.

Kidney decontamination during perfusion for transplantation procedure: In vitro and ex vivo viability analysis.

Organ transplantations have an increasing medical relevance. It is becoming a regular procedure with an increase in individuals waiting for organs. The increase in the number of discarded organs is mostly due to the donor bacterial and/or viral infection. In this article, we are demonstrating the feasibility of reduction of the bacterial load in kidney model by using ultraviolet-C as a germicidal agent in circulating liquids. Using Staphylococcus aureus as a bacteria model, we were able to demonstrate that in less than 30 min of liquid circulation and associated to irradiation, the bacterial load of the perfusate Custodiol HTK, histidine-tryptophan-ketoglutarate (solution with 5 log CFU mL-1 ), was fully eliminated. A modeling approach was created to verify the possibility of bacterial load decrease, when an organ (here, a renal experimental model) is present in the circuit, releasing a varied rate of microorganisms over time, while the solution is irradiated. Finally, we use an ex vivo model with swine kidney, circulating in the preservation solution with a Lifeport Kidney Transporter machine, to demonstrate that we can contaminate the organ and then promote the elimination of the microbiological load. The results show the feasibility of the technique.

Photodynamic and Sonodynamic Therapy with Protoporphyrin IX: In Vitro and In Vivo Studies.

Sono-photodynamic therapy is a promising anticancer technique based on the combination of sonodynamic and photodynamic therapy to improve the cancer treatment effectiveness. This study was aimed at analyzing the effects of the sono-photodynamic (SPD) activity on protoporphyrin IX (PpIX) solution and PpIX-loaded rat liver. In vitro, PpIX 5 µM solutions were irradiated with light (635 nm, 30-50 mW/cm2), ultrasound (1 MHz, 1-2 W/cm2) and both. The PpIX absorption spectra recorded over exposure time revealed that the PpIX decay rate induced by SPD activity (combined irradiation) was approximately the sum of those induced by photodynamic and sonodynamic activity. In vivo, rats were intraperitoneally injected with 5-aminolevulinic acid at the dose of 500 mg/kg weight. After 3 h of injection, the PpIX-loaded livers were irradiated with light (635 nm, 180 ± 9 J/cm2), ultrasound (1.0 MHz, 770 ± 40 J/cm2) and both using a single probe capable of illuminating and sonicating the liver simultaneously. After 30 h, the liver damage induced by each protocol was analyzed histologically. It was found that a greater necrosis depth was induced by the SPD activity. These results suggest that the SPD activity could improve the PpIX decay rate and have greater scope than photodynamic or sonodynamic activity. Further studies should be performed to gain a better understanding of this protocol.

Dissolving microneedles containing aminolevulinic acid improves protoporphyrin IX distribution.

One important limitation of topical photodynamic therapy (PDT) is the limited tissue penetration of precursors. Microneedles (MNs) are minimally invasive devices used to promote intradermal drug delivery. Dissolving MNs contain drug-associated to polymer blends, dissolving after insertion into skin, allowing drug release. This study comprises development and characterization of a pyramidal model of dissolving MNs (500 µm) prepared with 5% wt/wt aminolevulinic acid and 20% wt/wt Gantrez AN-139 in aqueous blend. Protoporphyrin IX formation and distribution were evaluated in tumor mice model by using fluorescence widefield imaging, spectroscopy, and confocal microscopy. MNs demonstrated excellent mechanical resistance penetrating about 250 µm with minor size alteration in vitro, and fluorescence intensity was 5-times higher at 0.5 mm on average compared to cream in vivo (being 10 ± 5 a.u. for MNs and 2.4 ± 0.8 a.u. for cream). Dissolving MNs have overcome topical cream application, being extremely promising especially for thicker skin lesions treatment using PDT.

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.

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.

Photodynamic therapy of extrahepatic cholangiocarcinoma using digital cholangioscopy.

BACKGROUND: Photodynamic therapy (PDT) of an extrahepatic cholangiocarcinoma using a digital cholangioscopy to deliver the laser. BACKGROUND: Cholangiocarcinoma is an aggressive neoplasm that usually requires palliative biliary drainage. Photodynamic therapy (PDT) has been described as a successful adjunct treatment to malignant biliary obstruction. AIM: To describe the use of digital cholangioscope to help provide laser light during biliary PDT session using locally developed light source. METHOD: Patient receives intravenous photosensitizer 24 h before the procedure. It starts with a regular duodenoscopy. After identification of the major papilla and retrograde cannulation, the digital cholangioscope is introduced into the common bile duct. Then, the cholangioscopic examination helps to identify the neoplastic stricture. Under direct visualization lighting catheter is advanced through the cholangioscope. Repositioning is recommended every centimeter to cover all strictured area. At the end of the procedure, a final cholangioscopy assesses the bile duct for the immediate result and adverse events. RESULT: This procedure was applied in one 82-year-old male due to obstructive jaundice in the last two months. EUS and ERCP revealed a severe dilation of the common bile duct associated with choledocholithiasis. Besides, was revealed dilation of hepatic duct up to a well-circumscribed hypoechoic solid mass measuring 1.8x2 cm compressing the common hepatic duct. The mass was deemed unresectable and the patient was referred for palliative treatment with PDT. He remained asymptomatic for three months. He perished due to complications 15 months after the PDT session. CONCLUSION: Digital cholangioscopy-guided biliary PDT is feasible and seems safe and effective as an adjunct modality in the palliation of extrahepatic cholangiocarcinoma.

A threshold dose distribution approach for the study of PDT resistance development: A threshold distribution approach for the study of PDT resistance.

Photodynamic therapy (PDT) is a technique with well-established principles that often demands repeated applications for sequential elimination of tumor cells. An important question concerns the way surviving cells from a treatment behave in the subsequent one. Threshold dose is a core concept in PDT dosimetry, as the minimum amount of energy to be delivered for cell destruction via PDT. Concepts of threshold distribution have shown to be an important tool for PDT results analysis in vitro. In this study, we used some of these concepts for demonstrating subsequent treatments with partial elimination of cells modify the distribution, which represents an increased resistance of the cells to the photodynamic action. HepG2 and HepaRG were used as models of tumor and normal liver cells and a protocol to induce resistance, consisted of repeated PDT sessions using Photogem® as a photosensitizer, was applied to the tumor ones. The response of these cells to PDT was assessed using a standard viability assay and the dose response curves were used for deriving the threshold distributions. The changes in the distribution revealed that the resistance protocol effectively eliminated the most sensitive cells. Nevertheless, HepaRG cell line was the most resistant one among the cells analyzed, which indicates a specificity in clinical applications that enables the use of high doses and drug concentrations with minimal damage to the surrounding normal tissue.

Optical techniques for the diagnosis and treatment of lesions induced by the human papillomavirus - A resource letter.

Human papillomaviruses (HPV) are the most common sexually-transmitted virus, and carcinogenic HPV strains are reported to be responsible for virtually all cases of cervical cancer and its precursor, the cervical intraepithelial neoplasia (CIN). About 30% of the sexually active population are considered to be affected by HPV. Around 600 million people are estimated to be infected worldwide. Diseases related to HPV cause significant impact from both the personal welfare point of view and public healthcare perspective. This resource letter collects relevant information regarding HPV-induced lesions and discusses both diagnosis and treatment, with particular attention to optical techniques and the challenges involved to the implementation of those approaches.

Prophylactic application of laser light restores L-FABP expression in the livers of rats submitted to partial ischemia.

OBJECTIVES: The objective of the present study was to evaluate the protective effect of pre-conditioning treatment with laser light on hepatic injury in rats submitted to partial ischemia using mitochondrial function and liver fatty acid binding protein as markers. METHODS: Rats were divided into four groups (n=5): 1) Control, 2) Control + Laser, 3) Partial Ischemia and 4) Partial Ischemia + Laser. Ischemia was induced by clamping the hepatic pedicle of the left and middle lobes of the liver for 60 minutes. Laser light at 660 nm was applied to the liver immediately prior to the induction of ischemia at 22.5 J/cm2, with 30 seconds of illumination at five individual points. The animals were sacrificed after 30 minutes of reperfusion. Blood and liver tissues were collected for analysis of mitochondrial function, determination of malondialdehyde and analysis of fatty acid binding protein expression by Western blot. RESULTS: Mitochondrial function decreased in the Partial Ischemia group, especially during adenosine diphosphate-activated respiration (state 3), and the expression of fatty acid binding protein was also reduced. The application of laser light prevented bioenergetic changes and restored the expression of fatty acid binding protein. CONCLUSION: Prophylactic application of laser light to the livers of rats submitted to partial ischemia was found to have a protective effect in the liver, with normalization of both mitochondrial function and fatty acid binding protein tissue expression.

Study of laser fluorescence spectroscopy in livers of rats with hypothermic ischemia

Purpose: After partial hepatectomy (PH), the remaining liver (RL) undergoes regenerative response proportional to the host. Limited literature exists on hepatic viability after tissue injury during hypothermic preservation. Spectroscopy measures cellular fluorescence and is explored for tissue characterization and parameter investigation. This study aimed to assess fluorescence analysis (spectroscopy) in evaluating liver viability and its relationship with hepatic tissue regeneration 24 hours after PH. Additionally, we analyzed liver regeneration in RL after 70% partial hepatectomy under hypothermic conditions with laser irradiation. Methods: Fifty-six Wistar rats were divided into four groups: total non-perfused liver (control), total perfused liver, partial hepatectomy "in situ", and partial hepatectomy "ex situ". Tissue analysis was performed at 0 and 24 hours using spectroscopy with laser devices emitting at 532 (green) and 405 nm (violet). Results: Spectroscopy identified tissue viability based on consistent results with Ki67 staining. The fluorescence spectra and Ki67 analysis displayed similar patterns, linking proliferative activity and absorption intensity. Conclusions: Fluorescence spectroscopy proves to be promising for real-time analysis of cellular activity and viability. Metabolic activity was observed in groups of live animals and hypothermically preserved samples, indicating cellular function even under blood deprivation and hypothermic conditions.

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.

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.

Photodynamic therapy of extrahepatic cholangiocarcinoma using digital cholangioscopy / Terapia fotodinâmica em colangiocarcinoma extra-hepático utilizando colangioscopia digital

ABSTRACT Background: Cholangiocarcinoma is an aggressive neoplasm that usually requires palliative biliary drainage. Photodynamic therapy (PDT) has been described as a successful adjunct treatment to malignant biliary obstruction. Aim: To describe the use of digital cholangioscope to help provide laser light during biliary PDT session using locally developed light source. Method: Patient receives intravenous photosensitizer 24 h before the procedure. It starts with a regular duodenoscopy. After identification of the major papilla and retrograde cannulation, the digital cholangioscope is introduced into the common bile duct. Then, the cholangioscopic examination helps to identify the neoplastic stricture. Under direct visualization lighting catheter is advanced through the cholangioscope. Repositioning is recommended every centimeter to cover all strictured area. At the end of the procedure, a final cholangioscopy assesses the bile duct for the immediate result and adverse events. Result: This procedure was applied in one 82-year-old male due to obstructive jaundice in the last two months. EUS and ERCP revealed a severe dilation of the common bile duct associated with choledocholithiasis. Besides, was revealed dilation of hepatic duct up to a well-circumscribed hypoechoic solid mass measuring 1.8x2 cm compressing the common hepatic duct. The mass was deemed unresectable and the patient was referred for palliative treatment with PDT. He remained asymptomatic for three months. He perished due to complications 15 months after the PDT session. Conclusion: Digital cholangioscopy-guided biliary PDT is feasible and seems safe and effective as an adjunct modality in the palliation of extrahepatic cholangiocarcinoma.

RESUMO Racional: Colangiocarcinoma é neoplasia agressiva que geralmente exige drenagem biliar paliativa. A terapia fotodinâmica (TFD) tem sido descrita como tratamento adjunto bem-sucedido para tratar obstrução biliar maligna. Objetivo: Descrever o emprego do colangioscópio digital para ajudar a fornecer luz de laser durante sessão de TFD biliar usando fonte de luz desenvolvida localmente. Método: Paciente recebe fotossensibilizador intravenoso 24 h antes do procedimento que começa com duodenoscopia regular. Após a identificação da papila principal e da canulação retrógrada, o colangioscópio digital é introduzido no ducto biliar comum. Em seguida, o exame colangioscópico ajuda a identificar a estenose neoplásica. Sob visualização direta, o cateter de iluminação avança através do colangioscópio. Reposicionamento é feito a cada centímetro. Ao final colangioscopia avalia o ducto biliar quanto ao resultado imediato e a eventos adversos. Resultado: Este procedimento foi aplicado em um homem de 82 anos devido à icterícia obstrutiva nos últimos dois meses. EUS e CPRE revelaram dilatação grave do ducto biliar comum associada à coledocolitíase. Além disso, havia dilatação do ducto hepático até massa sólida hipoecóica bem circunscrita, medindo 1,8x2 cm, comprimindo o ducto hepático comum. Ela foi considerada irressecável e paciente encaminhado para tratamento paliativo com TFD que permaneceu assintomático por três meses. Morreu devido a complicações 15 meses após a sessão de TFD. Conclusão: A TFD biliar guiada por colangioscopia digital é viável e parece segura e eficaz como modalidade auxiliar na paliação de colangiocarcinoma extra-hepático.

Prophylactic application of laser light restores L-FABP expression in the livers of rats submitted to partial ischemia

OBJECTIVES: The objective of the present study was to evaluate the protective effect of pre-conditioning treatment with laser light on hepatic injury in rats submitted to partial ischemia using mitochondrial function and liver fatty acid binding protein as markers. METHODS: Rats were divided into four groups (n=5): 1) Control, 2) Control + Laser, 3) Partial Ischemia and 4) Partial Ischemia + Laser. Ischemia was induced by clamping the hepatic pedicle of the left and middle lobes of the liver for 60 minutes. Laser light at 660 nm was applied to the liver immediately prior to the induction of ischemia at 22.5 J/cm2, with 30 seconds of illumination at five individual points. The animals were sacrificed after 30 minutes of reperfusion. Blood and liver tissues were collected for analysis of mitochondrial function, determination of malondialdehyde and analysis of fatty acid binding protein expression by Western blot. RESULTS: Mitochondrial function decreased in the Partial Ischemia group, especially during adenosine diphosphate-activated respiration (state 3), and the expression of fatty acid binding protein was also reduced. The application of laser light prevented bioenergetic changes and restored the expression of fatty acid binding protein. CONCLUSION: Prophylactic application of laser light to the livers of rats submitted to partial ischemia was found to have a protective effect in the liver, with normalization of both mitochondrial function and fatty acid binding protein tissue expression.