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 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).

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.

Photodynamic therapy: occupational hazards and preventative recommendations for clinical administration by healthcare providers.

OBJECTIVE: Photodynamic therapy (PDT) as a medical treatment for cancers is an increasing practice in clinical settings, as new photosensitizing chemicals and light source technologies are developed and applied. PDT involves dosing patients with photosensitizing drugs, and then exposing them to light using a directed energy device in order to manifest a therapeutic effect. Healthcare professionals providing PDT should be aware of potential occupational health and safety hazards posed by these treatment devices and photosensitizing agents administered to patients. MATERIALS AND METHODS: Here we outline and identify pertinent health and safety considerations to be taken by healthcare staff during PDT procedures. RESULTS: Physical hazards (for example, non-ionizing radiation generated by the light-emitting device, with potential for skin and eye exposure) and chemical hazards (including the photosensitizing agents administered to patients that have the potential for exposure via skin, subcutaneous, ingestion, or inhalation routes) must be considered for safe use of PDT by the healthcare professional. CONCLUSIONS: Engineering, administrative, and personal protective equipment controls are recommendations for the safe use and handling of PDT agents and light-emitting technologies.

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.

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.

[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.

[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.

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.

Research progress of the anti-tumor effect of sonodynamic and photodynamic therapy / 生物医学工程学杂志

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.

Denture stomatitis treated with photodynamic therapy: five cases.

OBJECTIVE: Photodynamic therapy (PDT) is an effective method for Candida spp. inactivation in vitro and in vivo, but as yet, no clinical trial has been conducted. This report describes 5 cases of denture stomatitis (DS) treated with PDT. STUDY DESIGN: Five subjects with clinical and microbiologic diagnosis of DS were submitted to 6 sessions of PDT 3 times a week for 15 days. In each session, patients' dentures and palates were sprayed with 500 mg/L Photogem, and, after 30 minutes of incubation, irradiated by light-emitting diode light source at 455 nm (37.5 and 122 J/cm(2), respectively). Cultures of Candida spp. from dentures and palates and standard photographs of the palates were taken at baseline (day 0), at the end of the treatment (day 15), and at follow-up time intervals (days 30 and 60). RESULTS: Four patients showed clinical resolution of DS (no inflammation) after PDT sessions, and only 1 subject demonstrated reduction in palatal inflammation. Recurrence of DS was observed in 2 patients during the follow-up period. CONCLUSIONS: PDT appears to be an alternative treatment for DS.

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.

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.

[Pigment epithelial detachment in exudative macular degeneration: clinical characteristics and therapeutic options]. / Pigmentepithelabhebung bei exsudativer Makuladegeneration: Klinische Charakteristika und therapeutische Optionen.

Vascularized pigment epithelial detachment (PE detachment) can be viewed as a special form of occult choroidal neovascularization (CNV) owing to the natural course of the disease, its specific pathogenesis and its response to various forms of treatment. This applies to serous PE detachment associated with both occult CNV and also with retinal angiomatous proliferation (RAP). A tear in the retinal pigment epithelium (RIP) represents a serious complication of vascularized PE detachment and is often associated with acute vision deterioration that not uncommonly also involves massive subretinal hemorrhaging. The pathomechanism underlying the development of RIP has not yet been completely elucidated. The notion that the PED bursts as a result of the increased pressure stands in contrast to the theory that the CNV contracts and causes scarring which in turn causing secondary RIP. Anti-VEGF therapy is currently the preferred treatment. However, the initial stabilization of visual acuity after treatment could not be confirmed in long-term studies and after 2 years visual acuity deteriorated significantly. Furthermore, optimal VEGF treatment regimens have also not been defined and the criteria for repeated treatment have not been established as yet. Presently, visual deterioration and the presence of subretinal and intraretinal exudates seem to indicate that treatment will be effective. Here, high resolution OCT imaging should help to provide further insight into the matter.

Photoactivated disinfection of Streptococcus intermedius through dentin disc at clinically relevant intervals: an in vitro study.

In this present study we have tested the impact of porfimer sodium (Photofrin, AXCAN PHARMA Inc., Quebec, Canada) photoactivated disinfection (PD) on cells of Streptococcus intermedius in suspension. In order to provide basic data to support future clinical studies of PD in dentistry the study used exposure to Quartz-tungsten-halogen (QTH) dental curing light for clinically relevant time periods to activate Photofrin and measured its effectiveness under a variety of conditions including activation through dentin hard tissue. S. intermedius was grown in planktonic suspension for 48h. Nine groups were formed: three control groups (1-3) and six experimental groups (4-9). Groups 4-6 tested the use of Photofrin treatment combined with QTH light at various intervals of irradiation (5, 15 and 60s). Groups 7-9 were similar to groups 4-6 with the exception that irradiation commenced through a dentin disc. Following treatment, bacteria were plated. Colony counts were measured following 72h incubation at 37 degrees C. Statistical analysis was carried out by one-way ANOVA at a 95% confidence level. A significant reduction in S. intermedius colony counts was observed for all experimental groups and one control group. The reduction in numbers of colonies in the experimental groups varied from 79.28 to 99.40% with an average of 94.61%. Reduction in viable bacterial cells indicated a strong relationship between power density and irradiation interval. When curing light energy density was lower due to the irradiation through the 1mm dentin disc, prolonged irradiation interval enhanced bacterial kill. In conclusion, where direct irradiation is not possible for PD treatment, irradiation through dentin may still be done successfully within a clinically relevant interval.

Oxidative alterations induced in vitro by the photodynamic reaction in doxorubicin-sensitive (LoVo) and -resistant (LoVoDX) colon adenocarcinoma cells.

In photodynamic therapy (PDT) a tumor-selective photosensitizer is administered and then activated by exposure to a light source of appropriate wavelength. Multidrug resistance (MDR) is largely caused by the drug efflux from the tumor cell by means of P-glycoprotein, resulting in reduced efficacy of the anticancer therapy. This study deals with photodynamic therapy with Photofrin (Ph) on colon cancer cell lines (doxorubicin-sensitive and -resistant). The cells were treated with 15 and 30 microg/mL Ph and then irradiated by a light dose of 3 or 6 J/cm(2) (632.8 nm). After irradiation the cells were incubated for 0, 3 or 18 h. Crucial factors of oxidative stress (thiobarbituric acid reactive substances [TBARS], protein damage, thiazolyl blue tetrazolium bromide [MTT] assay), changes in cytosolic superoxide dismutase (SOD1) activity after photodynamic reaction (PDR), and the intracellular accumulation of photosensitizers in the cells were examined. Moreover, the expressions of glutathione S-transferase (GST)-pi, a marker protein for photochemical toxicity, and secretory phospholipase A(2), a prognostic and diagnostic marker for colon cancers, were determined. After PDR, increases in SOD1 activity and the level of TBARS were observed in both cell lines. The level of protein-associated -SH groups decreased after PDR. Both cell lines demonstrated stronger GST-pi and PLA(2) expression after PDR, especially after 18 h of incubation. The increasing level of reactive oxygen species following the oxidation of sulfhydryl cell groups and lipid peroxidation influence the activity of many transporters and enzymes. The changes in SOD1 activity show that photodynamic action generates oxidative stress in treated cells. Our study presents that PDR caused oxidative alterations in both examined colon adenocarcinoma cell lines. However, the MDR cells reacted more slowly and all oxidative changes occurred in the delay.

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.

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.