Precancerous Skin Lesions. / Precáncer cutáneo.

Certain clinically and histologically recognizable skin lesions with a degree of risk of progression to squamous cell carcinoma have been traditionally grouped as precancerous skin conditions but now tend to be classified as in situ carcinomas. This consensus statement discusses various aspects of these lesions: their evaluation by means of clinical and histopathologic features, the initial evaluation of the patient, the identification of risk factors for progression, and the diagnostic and treatment strategies available today.

Side-by-side comparison of photodynamic therapy and pulsed-dye laser treatment of port-wine stain birthmarks.

BACKGROUND: Pulsed-dye laser (PDL)-mediated photothermolysis is the current standard treatment for port-wine stain (PWS) birthmarks. Vascular-targeted photodynamic therapy (PDT) might be an alternative for the treatment of PWS. OBJECTIVES: To compare clinical outcomes of PDT and PDL treatment of PWS. METHODS: Two adjacent flat areas of PWS lesions were selected from each of 15 patients (two male and 13 female; age 11-36 years) and randomly assigned to either single-session PDL or PDT. PDL was delivered using a 585-nm pulsed laser. PDT was carried out with a combination of haematoporphyrin monomethyl ether (HMME) and a low-power copper vapour laser (510.6 and 578.2 nm). Clinical outcomes were evaluated colorimetrically and visually during follow-up. RESULTS: A total of nine red PWS lesions and six purple PWS lesions were treated. For red PWS, colorimetric assessment showed that the blanching rates of PDL and PDT at 2 months ranged from -11% to 24% and 22% to 55%, respectively. For purple PWS, blanching rates of PDL and PDT ranged from 8% to 33% and 30% to 45%, respectively. Overall, there was a significant difference between the blanching effect of single-session PDL treatment and a single-session PDT treatment. CONCLUSIONS: This side-by-side comparison demonstrates that PDT is at least as effective as PDL and, in some cases, superior. The true value of PDT for the treatment of PWS deserves further investigation.

Efficacy and safety of photodynamic therapy with temoporfin in curative treatment of recurrent carcinoma of the oral cavity and oropharynx.

Therapeutic options for recurrent carcinoma of the upper aérodigestive tract (UADT) are limited. The prognosis of these tumours remains poor with significant rate of recurrence and a lower median survival time. Photodynamic therapy (PDT) is a relatively new therapeutic alternative which combines the use of a photosensitising agent and light to induce a cytotoxic effect on the tissues. This is a retrospective single-centre study carried out in patients with a recurrence of an oral cavity or oropharyngeal carcinoma or a second appearance of tumour in a previously irradiated area. There were no metastases in lymph nodes or other organs. Laser treatment was carried out 96 h after temoporfin (Foscan(®)) injection. In our series we had 14 cases with a complete response, 1 partial response. Overall survival at 1 year was 72 % and 36 % at 5 years. Disease-specific survival at 1 year was 82 % and 45 % at 5 years. Recurrence-free survival at 1 year was 52 % and 34 % at 5 years. Side effects mainly described are pain in the area of illumination, well controlled. PDT with Foscan(®) gives useful results in terms of survival and improvement in quality of life with few adverse events or severe complications. The fact that it has low toxicity and that treatment sessions can be repeated mean it should be considered in the therapeutic armamentarium for recurrent carcinoma of the UADT.

Hypericin-based photodynamic therapy induces surface exposure of damage-associated molecular patterns like HSP70 and calreticulin.

Surface-exposed HSP70 and calreticulin are damage-associated molecular patterns (DAMPs) crucially involved in modulating the success of cancer therapy. Photodynamic therapy (PDT) involves the administration of a photosensitising (PTS) agent followed by visible light-irradiation. The reactive oxygen species that are thus generated directly kill tumours by damaging their microvasculature and inducing a local inflammatory reaction. PDT with the PTS photofrin is associated with DAMPs exposure, but the same is not true for other PTSs. Here, we show that when cancer cells are treated with hypericin-based PDT (Hyp-PDT), they surface-expose both HSP70 and calreticulin (CRT). Induction of CRT exposure was not accompanied by co-exposure of ERp57, but this did not compromise the ability of the exposed CRT to regulate the phagocytosis of Hyp-PDT-treated cancer cells by dendritic cells. Interestingly, we found that Hyp-PDT-induced CRT exposure (in contrast to anthracycline-induced CRT exposure) was independent of the presence of ERp57. Our results indicate that Hyp-PDT is a potential anti-cancer immunogenic modality.

[Extrahepatic cholangiocarcinoma: current state of palliation therapy]. / Extrahepatische Gallenwegstumoren: aktueller Stand der palliativen Therapie.

INTRODUCTION: Decompression of bile ducts is the priority objective in the non-curative stage of hilar cholangiocarcinoma. Only this will prevent or slow down infectious complications and secondary biliary cirrhosis thereby sustaining the quality of life. KEY STATEMENTS: At present, photodynamic therapy combined with insertion of an endoprosthesis seems to be best documented and most appropriate therapy. METHODS: Data from a selective literature search combined with our clinical experience were evaluated. CONCLUSIONS: Therapeutic measures should match the dissemination and stage of the tumor: in locally advanced or progressing disease (stage III) a local ablating therapy, in systemically progressing disease (stage IV) systemic chemotherapy should be utilised.

[Research progress of the anti-tumor effect of sonodynamic and photodynamic therapy].

Cancer, as a serious threat to human health, is one of the major killers. The treatment of cancer has attracted more and more attention. Currently, the means of treating cancer is also increasing, but there is no emergence of a fully satisfactory treatment. A combination of sonodynamic therapy (SDT) and photodynamic therapy (PDT), named sono-photodynamic therapy (S-PDT), is a new composite cancer therapy. Because the therapy can significantly improve the tumor curing effect, it has good application prospects in cancer prevention and treatment. The present article reviewed the progress of the anti-tumor mechanisms and influencing factors of S-PDT.

Efficacy and safety of HpD-PDT for Extramammary Paget's Disease refractory to conventional therapy: A prospective, open-label and single arm pilot study.

BACKGROUND: Extramammary Paget's Disease (EMPD) is an intraepithelial cancer that is prone to recurrence and sometimes refractory to therapy. A few EMPD cases have been treated with Photodynamic therapy (PDT), which reported high complete remission (CR) rates and low recurrence with hematoporphyrin derivatives (HpD) The aim of this study was to further explore the efficacy and safety of HpD-PDT for EMPD patients. METHODS: Open-label, single arm, pilot study was designed to investigate the role of HpD-PDT in EMPD. The HpD sensitizer was given intravenously at a dose of 3 or 5 mg/kg 48 h before light irradiation with a laser 630 nm red light at a dose level of 150-200 J/cm2. Clinical parameters involving gender, age, disease course, previous treatment, tumor thickness, long diameter of lesion, TNM staging, EMPD staging, HpD dosage, Visual Analogue Scale (VAS) score, 1st month visit result, subsequent treatment, follow up period and endpoint outcomes were collected to evaluate efficacy and safety of the intervention. RESULTS: Eleven patients with pathologic confirmed EMPD were treated with HpD-PDT. The thickness of skin lesions which were located in vulva, penis, scrotum, and perianal area is 0.8∼6.7 mm (mean thickness 2.9 mm). All patients were followed up for an average of 17.4 months (12∼27 months). Complete remission (CR) rate and partial remission (PR) rate at the 1st month were 90.1% (10/11) and 9.1% (1/11) respectively. At the end of follow-up, 72.7% of the subjects (8/11) showed CR. Pain, infection, photosensitivity and uroschesis are recorded as adverse events (AEs) in this population, and no event of hepatic impairment was reported. After treatment, all the eleven patients showed different degrees of scar in the treatment site, but none of them had any structural or functional abnormalities. CONCLUSIONS: According to our study, HpD-PDT in EMPD is able to offer acceptable disease outcomes including relatively high CR rate, with good cosmetic and functional outcomes, and could be considered a potential recommended therapy for patients with EMPD. TRIAL REGISTRATION: Chinese Clinical Trial Register (ChiCTR-1900024965).

Photodynamic therapy of intravenous injection combined with intratumoral administration of photosensitizer in squamous cell carcinoma.

Cutaneous squamous cell carcinomas (cSCC) is one of the most common types of non-melanoma skin cancer (NMSC), and surgical excision is the primary regimen in most cases. However, in some circumstances of special lesion locations like lips, eyelids or vulva, old age or patient choice non-surgical therapy may be alternative. This is a case of one 93-year-old female cSCC patient who declined surgery. Treatment of hematoporphyrin derivatives photodynamic therapy (HpD-PDT) consisting of both intravenous and topical photosensitizers plus red light irradiation was prescribed. Clinical remission was achieved without evidence of recurrence and most cosmetic function was preserved.

Efficacy and safety of hemoporfin in photodynamic therapy for port-wine stain: a multicenter and open-labeled phase IIa study.

BACKGROUND/PURPOSE: This phase IIa study aimed to study the efficacy and safety of hemoporfin in photodynamic therapy (PDT) with a 532 nm continuous laser for port-wine stain (PWS). METHODS: In this 8-week open-labeled study in three centers, three different laser exposure times (532 nm continuous laser for 20, 30 and 40 min) were used in stage I, group A, stage II, group B and stage III, group C, respectively. Primary efficacy assessment was performed by an independent group of experts, who reviewed the standardized photos. Secondary efficacy assessment consisted of the subjective grading of the PWS fading by the investigators and the patients. Treatment reactions and adverse events (AE) were recorded separately. RESULTS: Forty patients were initially enrolled in the study, but stage III had to be cancelled eventually for the safety of the patients. Patients in groups A and B showed similar satisfactory results in efficacy assessments, the total 'response' rate being 80.0% and 94.7% in groups A and B, respectively. The AE rates were also similar in the two groups. Self-limiting photosensitive dermatitis and hyperpigmentation were the most frequently observed AE. CONCLUSION: Hemoporfin-PDT is effective and safe for patients with PWS aged 16-50.

Photodynamic therapy using intra-articular Photofrin for murine MRSA arthritis: biphasic light dose response for neutrophil-mediated antibacterial effect.

BACKGROUND AND OBJECTIVE: Bacterial arthritis does not respond well to antibiotics and moreover multidrug resistance is spreading. We previously tested photodynamic therapy (PDT) mediated by systemic Photofrin® in a mouse model of methicillin-resistant Staphylococcus aureus (MRSA) arthritis, but found that neutrophils were killed by PDT and therefore the infection was potentiated. STUDY DESIGN/MATERIALS AND METHODS: The present study used an intra-articular injection of Photofrin® and optimized the light dosimetry in order to maximize bacterial killing and minimize killing of host neutrophils. MRSA (5 × 10(7) CFU) was injected into the mouse knee followed 3 days later by 1 µg of Photofrin® and 635-nm diode laser illumination with a range of fluences within 5 minutes. Synovial fluid was sampled 6 hours or 1-3, 5, and 7 days after PDT to determine MRSA colony-forming units (CFU), neutrophil numbers, and levels of cytokines. RESULTS: A biphasic light dose response was observed with the greatest reduction of MRSA CFU seen with a fluence of 20 J cm(-2), whereas lower antibacterial efficacy was observed with fluences that were either lower or higher. Consistent with these results, a significantly higher concentration of macrophage inflammatory protein-2, a CXC chemokine, and greater accumulation of neutrophils were seen in the infected knee joint after PDT with a fluence of 20 J cm(-2) compared to fluences of 5 or 70 J cm(-2). CONCLUSION: PDT for murine MRSA arthritis requires appropriate light dosimetry to simultaneously maximize bacterial killing and neutrophil accumulation into the infected site, while too little light does not kill sufficient bacteria and too much light kills neutrophils and damages host tissue as well as bacteria and allows bacteria to grow unimpeded by host defense.

Prevalence and predictors of recurrent neoplasia after ablation of Barrett's esophagus.

BACKGROUND: The incidence and risk factors for recurrence of dysplasia after ablation of Barrett's esophagus (BE) have not been well defined. OBJECTIVE: To determine the rate and predictors of dysplasia/neoplasia recurrence after photodynamic therapy (PDT) in BE. SETTING: Retrospective analysis of a prospective cohort of BE patients seen at a specialized BE unit. METHODS: Patients underwent a standard protocol assessment with esophagogastroduodenoscopy and 4-quadrant biopsies every centimeter at 3-month intervals after ablation. Recurrence was defined as the appearance of any grade of dysplasia or neoplasia after 2 consecutive endoscopies without dysplasia. Entry histology, demographics, length of BE, presence and length of diaphragmatic hernia, EMR, stricture formation, nonsteroidal anti-inflammatory drug use, smoking, and the presence of nondysplastic BE or squamous epithelium were assessed for univariate associations. Time-to-recurrence analysis was done by using Cox proportional hazards regression. A multivariate model was constructed to establish independent associations with recurrence. RESULTS: A total of 363 patients underwent PDT with or without EMR. Of these, 261 patients were included in the final analysis (44 lost to follow-up, 46 had residual dysplasia, and 12 had no dysplasia at baseline). Indication for ablation was low-grade dysplasia (53 patients, 20%), high-grade dysplasia (152 patients, 58%), and intramucosal cancer (56 patients, 21%). Median follow-up was 36 months (interquartile range 18-79 months). Recurrence occurred in 45 patients. Median time to recurrence was 17 months (interquartile range 8-45 months). Significant predictors of recurrence on the multivariate model were older age (hazard ratio [HR] 1.04, P=.029), presence of residual nondysplastic BE (HR 2.88, P=.012), and a history of smoking (HR 2.68, P=.048). LIMITATIONS: Possibility of missing prevalent dysplasia despite aggressive surveillance. CONCLUSION: Recurrence of dysplasia/neoplasia after PDT ablation is associated with advanced age, smoking, and residual BE.

The attenuation effect of 3,4-dihydroxy-phenyl lactic acid and salvianolic acid B on venular thrombosis induced in rat mesentery by photochemical reaction.

3,4-dihydroxy-phenyl lactic acid (DLA) and salvianolic acid B (SAB) are two major water-soluble components of Salvia miltiorrhiza (SM). Previous works have revealed the ability of DLA and SAB to scavenge oxygen free radicals, inhibiting the expression of adhesion molecules CD11b/CD18 in neutrophil. Cardiotonic pills (CP), which is a traditional Chinese medicine compound preparation containing DLA and SAB, was found to inhibit venular thrombosis induced by photochemical reaction (PR) in rat mesentery. The present study addressed the effect of DLA and SAB on PR-induced thrombosis in rat mesentery by utilizing a microcirculation dynamic viewing system. The result demonstrated that both DLA and SAB delayed thrombus-initiation time, while DLA also prolonged thrombus half-size time. The experiments explored the mechanism underlying that the dihydrorhodamine 123 (DHR) fluorescence in the mesenteric venular walls after PR challenge was diminished by pretreatment with either DLA or SAB, the expression of CD18 in neutrophils elicited by PR was depressed by administration of DLA, while mast cell degranulation in rat mesentery induced by PR was damped by SAB. The antioxidant potential of the two substances is likely to be responsible for their most beneficial effects on thrombosis, through either directly scavenging the peroxides produced and/or indirectly depressing the expression of adhesion molecules in neutrophil.

Hematoporphyrin-based photodynamic therapy for cutaneous squamous cell carcinoma in cats.

Photodynamic therapy (PDT) using a haematoporphyrin derivative (Photogem, General Physics Institute and clustes Ltda) as photosensitizer and light emitting diodes (LEDs) as the light source was evaluated in 12 cats with cutaneous squamous cell carcinoma. Lesions were illuminated with LEDs, (300 J/cm for 30 min) 24 h after the administration of the photosensitizer. Clinical responses were classified as complete disappearance of the tumour with total re-epithelialization; partial response (a reduction greater than 50%); and no response (less than 50% reduction). Tumours localized to the pinna treated with one (n = 3) or two (n = 4) applications of PDT yielded no response. Highly invasive tumours of the nose and nasal planum also showed no response, after two treatments (n = 2). A combination of PDT and surgery was performed in three cases. Two cats showed partial response and one complete response with one application of therapy 30 days after nasal surgery. Small and noninfiltrative lesions (n = 3) of the nasal planum showed a PR with one application (n = 2) and a CR with two applications (n = 1). This study shows that PDT using Photogem and LEDs can provide local control of low-grade feline squamous cell carcinoma. The addition of PDT to surgery in more invasive cases may help prevent recurrence.

Drug-induced photosensitivity.

(1) Photosensitivity reactions are cutaneous disorders due to exposure to ultraviolet (UV) radiation of natural or artificial origin. They occur or are more prevalent on unprotected skin. The main clinical manifestations are burns, eczema-like rash, urticaria, pigmentation, or onycholysis; (2) Many drugs increase cutaneous sensitivity to UV, sometimes for therapeutic purposes, but it is generally an unwanted effect.

New treatments for age-related macular degeneration.

As the estimated life expectancy of the U.S. population increases, so will the incidence of age-related macular degeneration (AMD). Exudative (or "wet") AMD, which is characterized by choroidal neovascularization, carries a high risk of extreme central vision loss and can severely compromise an individual's independence and quality of life. The increasing burden of AMD has created an acute need for more effective treatments. During the last several years, treatment of exudative AMD with intravitreal injection of antivascular endothelial growth factor (anti-VEGF) has dramatically reduced the severe visual loss usually associated with this disorder. This article summarizes the clinical presentation of AMD and reviews the treatments that are currently available.

Photodynamic therapy for Barrett's esophagus: does light still have a role?

Photodynamic therapy was the first treatment to have been shown to significantly decrease high-grade dysplasia and cancer in patients with Barrett's esophagus. However, its use has been limited, primarily because of the side effects, which include esophageal strictures, cutaneous photosensitivity, chest pain, and nausea and vomiting. The tolerability aspects of photodynamic therapy, as well as the dosimetry, though, can be improved with existing technologies to further develop this therapy into truly a widely applicable therapy. Studies have recently been done to help identify patients more likely to suffer stricture after photodynamic therapy. In addition there has been evidence to suggest that the efficacy of photodynamic therapy also can be limited by genetic abnormalities in the mucosa. By combining knowledge of tissue biology, optical properties of the tissue, and dosimetry issues with ablation, photodynamic therapy can still have a potentially bright future.

The use of photodynamic therapy for diseases of the esophagus.

This is a review of the uses, history, and current status of photodynamic therapy for diseases of the esophagus, specifically Barrett's dysplasia and early esophageal carcinoma. This paper describes the clinical experience of photodynamic therapy and compares the use of various photosensitizer drugs. Finally, important biophotonics developments are discussed, including their anticipated impact for improved endoscopic detection of dysplasia and carcinoma. In addition, methods for real-time photodynamic therapy and light dosimetry are provided in order to optimize ablation treatment outcomes while minimizing the risk of complications.

Factors associated with increased survival after photodynamic therapy for cholangiocarcinoma.

BACKGROUND & AIMS: Recent studies have shown a survival advantage using photodynamic therapy (PDT) in patients with unresectable cholangiocarcinoma. Factors associated with increased survival after PDT are unknown. METHODS: Twenty-five patients with cholangiocarcinoma who were treated with PDT at the Mayo Clinic Rochester from 1991 to 2004 were studied. Porfimer sodium (2 mg/kg) was administered intravenously to patients with Bismuth type I (3 patients), type III a/b (13 patients), and type IV (9 patients) tumors. Forty-eight hours later, PDT was administered using a 1.5- to 2.5-cm diffusing fiber that was advanced across the tumor by either retrograde (20 patients) or percutaneous (5 patients) cholangiography. Laser light was applied for a total energy of 180 J/cm2 in 1-3 applications. Patients received PDT treatments every 3 months. Plastic biliary stents (10-11.5 F) were inserted to decompress the biliary system after PDT. Survival analysis was performed using Kaplan-Meier curves and Cox proportional hazards models. RESULTS: Patients were 64 (standard error of the mean, +/-2.6) years of age; 20 (80%) were men. The median overall survival period was 344 days. The median survival period after PDT was 214 days. The 1-year survival rate was 30%. On multivariate analysis, the presence of a visible mass on imaging studies (hazard ratio, 3.55; 95% confidence interval, 1.21-10.38), and increasing time between diagnosis and PDT (hazard ratio, 1.13; 95% confidence interval, 1.02-1.25) predicted a poorer survival rate after PDT. A higher serum albumin level (hazard ratio, 0.16; 95% confidence interval, 0.04-0.59) predicted a lower mortality rate after PDT. CONCLUSIONS: Patients with unresectable cholangiocarcinoma without a visible mass may benefit from earlier treatment with PDT.

Influence of heating on the activity of xanthine oxidase in tumor cells subjected to the phototoxic action of hematoporphyrin derivative.

The aim of this study was to clarify the mechanism of the stimulatory effect of heat stress on generation of superoxide radical (O2-*) in tumors subjected to photodynamic therapy (PDT) with hematoporphyrin derivative (HPD). For this purpose, the effect of heating on the activity of xanthine oxidase (XOD) in tumor cells upon their photosensitization with HPD was examined; this enzyme is participated in purine catabolism and has the ability to generate O2-*, a precursor of H2O2 and very cytotoxic hydroxyl radical. The study was carried out on Ehrlich ascites carcinoma (EAC) cells, which were loaded with HPD in a serum-free medium and then irradiated with red light (lambda max = 630 nm) at 3 different temperatures (30, 37 and 44 degrees C). In the cells, the activity of XOD was assayed fluorometrically, using pterine as the substrate, whereas the production of O2-* by the nitro blue tetrazolium method. It was found that increasing of the temperature from 30 to 44 degrees C strongly (by approximately 2.5-fold) enhanced the generation of O2-* in EAC cells that correlated well with an increase in the rate of their photosensitized killing. Experiments showed that the intensification of O2-* formation could be mediated by the stimulatory effects of heating on the activity of XOD; namely, the 12 min treatment of EAC cells by HPD-PDT at a control (30 degrees C) temperature caused an about 2-fold growth in the activity of XOD, whereas the same light exposure at 44 degrees C led already to a 2.7-fold increase in the activity of this enzyme. However, incubation of EAC cells in the dark even at a hyperthermic (44 degrees C) temperature had no effect on their XOD activity. Thus, our findings strongly suggest that upon PDT with HPD the mild hyperthermia (approximately 44 degrees C) produced by photoirradiation might enhance the PDT-induced oxidative stress and, as a result, its tumoricidal effect via a rise in the activity of XOD. Besides, the obtained results suggest that severe hyperthermia (> 45 degrees C) could induce, contrary to mild hyperthermia, a reduction in the efficiency of HPD-PDT; we found that in EAC cells the raising temperature of an environment from 30 to 44 degrees C induced more than 2-fold increase in the activity of XOD, whereas further heating from 44 to 60 degrees C led to inactivation of this enzyme.