Photodynamic therapy in the management of basal cell carcinoma: Retrospective evaluation of outcome

IntroductionPhotodynamic therapy (PDT) is a relatively new method of treating various kinds of pathologies. In this retrospective study, a total of 148 patients with basal cell carcinoma (BCC) were treated with surface illumination methyl aminolevulinate – photodynamic therapy (MAL-PDT) or meta-tetrahydroxyphenylchlorin (mTHPC-PDT). Comparisons with the clinical features, rate of recurrence and overall outcome were made.Materials and methodsSurface illumination PDT was offered under local or general anaesthesia. For thin BCCs, the 16% strength cream (MAL) was applied topically 3 h prior to tissue illumination. A single-channel 628 nm diode laser was used for illumination and light was delivered at 100J/cm² per site. For thick BCCs, 0.05 mg/kg mTHPC was administered intravenously prior to tissue illumination. A single-channel 652 nm diode laser was used for illumination and light was delivered at 20J/cm² per site. Lesion response evaluation was carried out according to RECIST.ResultsThe MAL-PDT sub-group included 86 patients with 127 thin BCCs; 80 patients had complete response (CR) after one round of treatment. The mTHPC-PDT sub-group included 62 patients with 116 thick BCCs; 60 patients had complete response after one round of treatment. Statistically significant factors associated with complete response to MAL-PDT included superficial BCC histotype (P < 0.001), ≤0.5 mm tumour thickness (P < 0.001) and lack of ulceration (P < 0.001). While for the mTHPC-PDT sub-group, both superficial and nodular types responded significantly better than invasive type (P < 0.001); the lack of ulceration was insignificant factor in achieving complete response.ConclusionPDT achieved high efficacy in the treatment of basal cell carcinomas with greatly reduced morbidity and disfigurement. The technique is simple, can commonly be carried out in outpatient clinics, and is highly acceptable to patients.     

Endobronchial photodynamic therapy under fluorescence control: Photodynamic theranostics

BackgroundPhotodynamic therapy (PDT) has several advantages. However, one of the disadvantages is its inability to be individualized according to biological characteristics of malignant tumors. The objective of this study was to investigate a strategy for individualized endobronchial PDT in the treatment of centrally located non-small cell lung cancer.MethodsNew approach suggests taking fluorescence-based measurements of chlorine E6 photosensitizer (PS) accumulation in the malignant tumor tissue, and assess PS consumption rate during PDT. Two randomized groups of 45 patients took part in the comparative study of standard PDT procedure, 662 nm, pulse-periodic mode, therapeutic light (reference group – RG) versus the investigated individualized approach under fluorescence control after irradiation with violet light, 408 nm, diagnostic light (study group – SG). The PDT-treatment parameters and results of follow-up bronchoscopy were compared between the groups.Results43 (96%) of 45 patients in SG demonstrated intense fluorescence in the area of the tracheal/bronchial tumor stenosis. 4 (9%) of 45 patients (SG) demonstrated fluorescence of mucosa areas distant from the main tumor lesion after violet light irradiation. Mean fluence during the whole PDT procedure was 95 ± 20 J/cm² (range 60–130 J/cm²), which was significantly lower than in RG (p = 0.01). Total exposure time was significantly lower in SG (365 ± 65 s), compared with RG (690 ± 65 s), P = 0.001. According to the follow-up bronchoscopy the difference in the PDT-treatment results between the groups is statistically insignificant.ConclusionsThe investigated strategy suggests using fluorescence control of the efficacy of PDT-treatment (photodynamic theranostics) to optimize and individualize the PDT procedure.     

Sub-additive effects of photodynamic therapy combined with erlotinib for the treatment of epidermoid carcinoma: An in vitro study

BackgroundPhotodynamic therapy (PDT) is an antitumour treatment that employs the combination of a photosensitive compound, oxygen and visible light. To improve the antitumour activity of PDT, the present study used the strategy of combining PDT with erlotinib (ERL), a drug frequently used in the treatment of epidermoid carcinoma.MethodsAn MTT cell viability assay was used to evaluate the cytotoxicity of PDT combined with ERL on A431 epidermoid carcinoma cells in vitro. This study evaluated the cytotoxicity of the following treatments: red laser irradiation (660 nm) at different power densities (1.25–180 J/cm²), the photosensitizer methylene blue (MB) at concentrations of 0.39–100 μM, PDT (12.5 μM MB and laser power densities from 1.25 to 180 J/cm²), and PDT (12.5 μM MB and a laser density of 120 J/cm²) plus ERL (1 μM).ResultsThe laser power densities that were tested showed no cytotoxicity in A431 cells. MB showed a dose-dependent cytotoxicity. In PDT, an increase in the dose of light resulted in an increase in the cytotoxicity of MB. In addition, there was a sub-additive effect between PDT and ERL compared to the effect of each therapy alone.ConclusionsThe sub-additive effect between PDT and ERL suggests that their combination may be an important strategy in the treatment of epidermoid carcinoma.     

Photodynamic therapy using methylene blue in lung adenocarcinoma xenograft and hamster cheek pouch induced squamous cell carcinoma

BackgroundPhotodynamic therapy (PDT) is used to treat early proximal bronchial cancer during a flexible bronchoscopy. The technique relies on the excitation of a photosensitizer by an appropriate wavelength, which is delivered into the bronchus in close contact with the tumor.ObjectiveTo assess methylene blue (MB) as a PDT agent for the treatment of respiratory tract cancer in animal models.MethodsMB-induced PDT was performed on 7 subcutaneous NCI-H460 lung adenocarcinoma xenografts in nude mice and 9 induced squamous cell cancer in the hamster cheek pouch model. In mice, PDT was carried out on right-sided tumors after intratumoral injection of methylene blue 1% (w/v) and illumination at 630 nm at 200 J/cm (Diomed PDT 630), with the left tumor used as control (illumination alone or MB alone). The tumoral volume was assessed before and 15 days after PDT.ResultsFourteen xenografts were treated in mice, including seven treated with MB-PDT, producing a 52% mean tumor volume regression (1568 mm³ vs. 544 mm³) compared to seven control cases in which tumor volume increased (p = 0.007; Mann-Whitney test). Nine cheek pouch induced carcinomas were treated in the hamster group, with a mean volume decrease of 85.8% (from 44.8% to 100%) (initial mean volume = 210 mm³ vs. post PDT mean volume = 97 mm³). Histology analysis showed 4/9 complete responses.ConclusionIntratumoral MB appears efficient as PDT agent for cancer treatment in animal models. Further studies are needed to assess the safety and efficacy of MB-associated PDT for the treatment of lung cancer in humans.     

A randomized split-face clinical trial analyzing daylight photodynamic therapy with methyl aminolaevulinate vs ingenol mebutate gel for the treatment of multiple actinic keratoses of the face and the scalp

IntroductionDaylight photodynamic therapy with methyl aminolaevulinate (dlPDT) and ingenol mebutate gel (IMB) are approved therapeutic options for multiple actinic keratoses (AKs).The aim of this comparative, intra-patient, split-face, randomized clinical trial was to compare treatment outcomes of dlPDT and IMB.MethodsTwo symmetrical contralateral areas of 25 cm², harboring a similar (5–10) number of AKs, were selected and randomly assigned either to a 3 days’ IMB treatment cycle or to a single session of dlPDT. The day after the local skin reaction (LSR) score was registered. Patients’ scored pain (assessed through VAS method) after the treatment, and time needed for wound closure, were subsequently registered. After 90 days, the complete remission (CR) rate recorded for both single lesions and patients, the cosmetic outcome and the patients’ preference, were assessed.Results22 patients with a total of 311 AKs were enrolled. The mean pain VAS score was 3.55 ± 1.82 with IMB and 2.05 ± 0.72 with dlPDT (p < 0.01). The mean LSR score was 9.91 ± 4.24 and 4.59 ± 4.03 (p < 0.01), respectively. The mean days necessary for wound closure were 9.45 ± 3.51 and 4.36 ± 1.18 days (p < 0.01), respectively. After 3 months, 119 lesions with IMB and 120 lesions with dlPDT were healed and the CR rate with IMB (75.8%) was non-inferior to the CR rate with dlPDT (77.9%). The comparisons of CR rates of grade I and II AKs did not show any inferiority for one treatment compared to the other. Eight patients (36.4%) had all lesions cleared with IMB and 7 (31.8%) with dlPDT (p = NS). The cosmetic outcome was better with dlPDT and 17 patients evaluated dlPDT as their preferred treatment.ConclusionsA 3 days’ treatment cycle with IMB and a single session of dlPDT had a similar efficacy for both grade I AKs and grade II AKs but dl PDT showed lower pain and inflammation scores, quicker wound closure, better cosmetic outcome and higher patients’ preference.     

Phototoxicity in a laryngeal cancer cell line enhanced by a targeting amphiphilic chlorin photosensitizer

BackgroundPhotodynamic therapy (PDT) has been established in several countries as an alternative therapy for the treatment of various malignancies. This therapy involves the incorporation of a photosensitizer (PS) that is activated by visible light and form reactive oxygen species leading to target cell death by apoptosis or necrosis. Previously, our group has demonstrated that CHL-T (semi-synthesized from chlorophyll a and containing a linked solubilizing group TRISMA^®) presented a pronounced potential to induce death in HeLa cell line after PDT. In the present study, besides confirm the high cytotoxicity in another cell line, we have further investigated the cell death mechanisms caused by CHL-T as a photosensitizer in laryngeal carcinoma cells.MethodsCells were exposed to different concentrations of three photosensitizers, namely, hypericin (HY), unmodified chlorin (CHL) and a synthesized amphiphilic chlorin derivative (CHL-T). PSs accumulation and localization were accessed by fluorescence assays. Photosensitization was induced at 6 J cm⁻² using red LEDs (630 ± 10 nm). Viability was assessed by mitochondrial function (MTT); whereas apoptosis/necrosis was evaluated by fluorescence microscopy and flow cytometry. Expression of pro-apoptotic p53 protein was studied by Western blot.Results and conclusionsAll PS showed similar localization profile in the HEp-2 cells. The use of CHL-T increased the percentage of apoptotic cells and also p53 expression in comparison with the use of HY and CHL as photosensitizers. This study shows a significant effect of CHLT associated with red light (630 ± 10 nm and 18 mW cm⁻²) irradiation on a cancer cell line, indicating the potential of this amphiphilic chlorin in enhancing the therapeutic effectiveness of Photodynamic Therapy (PDT).     

Photodynamic therapy using Photofrin and excimer dye laser treatment for superficial oral squamous cell carcinomas with long-term follow up

ObjectivesPhotodynamic therapy (PDT) is a very effective treatment for superficial malignancies that does not result in loss of normal tissue. Here, we report successful PDT treatment of superficial oral cancers and its clinical outcome with long-term follow up.Materials and methodsThirty-four superficial oral squamous cell carcinomas were treated with PDT, and the effects were evaluated. Each patient received Photofrin (2 mg/kg) intravenously 48 h prior to light irradiation. Photoradiation was performed at doses of 100–150 J/cm² using a 630-nm wavelength excimer dye laser.ResultsSix months after PDT, 30 patients (88.2%) showed complete responses while 9 patients (26.5%) had local relapses during long-term follow-up. The 5-year overall survival, disease-specific survival, and disease-free survival rates were 76.5%, 84.6%, and 63.3%, respectively. Lesions with red patches had a significantly higher recurrence rate than lesions with white patches. Accurate evaluation of the extent of lesions and appropriate photoradiation were important in improving outcomes. Adverse events observed included sunburn and sequestrum formation of alveolar bone. No abnormal laboratory values or systemic complications were observed.ConclusionPDT using Photofrin as the photosensitizer is an effective treatment modality for superficial oral carcinomas, with excellent healing and minimal side effects.     

Antimicrobial photodynamic therapy (aPDT) and photobiomodulation (PBM – 660 nm) in a dog with chronic gingivostomatitis

Chronic gingivostomatitis in dogs is an inflammatory syndrome of the oral cavity, which treatment and control of concomitant periodontitis allow healing in most of the cases. In the presence of recurrent lesions, invasive methods are necessary to treat lesions and pain. As a conservative adjuvant method, photobiomodulation (PBM) with low power laser is able to promote reduction of tissue pain and tissue inflammation besides increasing vascularization and healing, restoring the normal function of the irradiated organ in a shorter time. In veterinary medicine, there is no standardization of technique for its use in oral tissue for treating gingivostomatitis in dogs. In the present case, a dog was submitted to aPDT (7.2 J/point, 3 min/point, 180 J/cm²) and PBM (1.6 J/point, 40 s/point, 25 J/cm²), using a semiconductor diode laser, with wavelength of 660 nm, spot size of ​​0.04 cm² and output power of 40 mW. The established protocol proved to be effective as coadjutant treatment for chronic gingivostomatitis, restoring the integrity of dog’s affected mucosa and gingiva.     

Effects of photodynamic therapy with talaporfin sodium on squamous cell carcinoma and sarcoma cells

BackgroundPhotodynamic therapy (PDT) uses a photosensitizer and light to destroy abnormal cells. Talaporfin sodium (NPe6) is a second-generation photosensitizer.MethodsWe evaluated the toxic effects of different combinations of laser and NPe6 doses on squamous cell carcinoma (KLN205) and sarcoma (Meth A) cell lines. The cells were incubated with 0, 5, 10, or 30 μg/mL NPe6 for 24 h. The cells were then irradiated with 0, 5, 15, or 30 mW/cm² of laser power, and 0, 1, 5, 10, or 20 J/cm² of laser energy. Cell viability was evaluated after 24 h. We also evaluated the cytotoxic effects of continuous wave or square-wave modulated laser irradiations (2, 5, or 10 Hz, 50% duty) on Meth A cells.ResultsThe median lethal doses of NPe6 against the KLN205 and Meth A cells after treatment at a fluence rate of 15 mW/cm² and a light dose of 20 J/cm² were 18.6 and 5.0 μg/mL, respectively. Meth A cells were more sensitive to PDT than KLN205 cells. There was no significant difference between the effects of continuous wave and square-wave modulated lasers on Meth A cell viability.ConclusionsNPe6 PDT induced cell death in a dose-dependent manner in KLN205 and Meth A cells. More work is required to evaluate the cytotoxic effects of square-wave modulated laser therapy at low light doses.     

Radiofrequency Coil for the Creation of Large Ablations: Ex Vivo and In Vivo Testing

PurposeVarious radiofrequency (RF) ablation electrode designs have been developed to increase ablation volume. Multiple heating cycles and electrode positions are often required, thereby increasing treatment time. The objective of this study was to evaluate the performance of a high-frequency monopolar induction coil designed to produce large thermal lesions (>3 cm) with a single electrode insertion in a treatment time of less than 10 minutes.Materials and MethodsA monopolar nitinol interstitial coil operated at 27.12 MHz and 200 W was evaluated. Ex vivo performance was tested in excised bovine liver (n=22). In vivo testing (n=10) was conducted in livers of seven Yorkshire pigs. Visual inspection, contrast-enhanced computed tomography (CT), and pathologic evaluation of ablation zones were performed.ResultsAverage ablation volumes in ex vivo and in vivo tests were 60.5 cm³±14.1 (5.9×4.4×4.4 cm) and 57.1 cm³±13.8 (6.1×4.5×4.1 cm), with average treatment times of 9.0 minutes±3.0 and 8.4 minutes±2.7, respectively. Contrast-enhanced CT ablation volume measurements corresponded with findings of gross inspection. Pathologic analysis showed morphologic and enzymatic changes suggestive of tissue death within the ablation zones.ConclusionsThe RF ablation coil device successfully produced large, uniform ablation volumes in ex vivo and in vivo settings in treatment times of less than 10 minutes. Ex vivo and in vivo lesion sizes were not significantly different (P=.53), suggesting that the heating efficiency of this higher-frequency coil device may help to minimize the heat-sink effect of perfusion.     

Effects of root debridement and adjunctive photodynamic therapy in residual pockets of patients on supportive periodontal therapy: A randomized split-mouth trial

BackgroundThe study aims to compare the effects of adjunctive photodynamic therapy (PDT) with scaling and root debridement alone on periodontal parameters and inflammatory cytokines in residual pockets of patients undergoing maintenance therapy.Methods27 subjects, each with at least 2 residual pockets ≥5 mm, were recruited for this randomized, split-mouth controlled trial, providing total of 72 sites. Probing pocket depth (PPD), recession, clinical attachment loss (CAL), plaque and bleeding on probing of all sites were examined at baseline, 3 and 6 months. Gingival crevicular fluids (GCFs) were collected to determine levels of IL-1β, IL-6, IL-8, TNF-α and MMP-8 via enzyme-linked immunosorbent assay. At baseline, all sites received subgingival instrumentation and polishing. In addition, test sites received a single application of PDT using Fotosan^® with toluidine blue O solution photosensitizer. At 3 and 6 months, site level analysis was performed for changes in clinical parameters and cytokine level.ResultsBased on mixed model analysis, at 3 months, test sites showed significant reduction in CAL (p = 0.016) and PPD (p = 0.027) (from 6.14 ± 0.28 mm to 5.49 ± 0.20 mm and 5.42 ± 0.16 mm to 4.65 ± 0.18 mm respectively) compared to control sites (from 6.32 ± 0.24 mm to 6.08 ± 0.17 mm and 5.32 ± 0.13 mm to 5.15 ± 0.15 mm respectively). At 6 months, these differences were no longer significant (p = 0.510). Adjunctive PDT did not offer additional reduction in levels of GCF cytokines.ConclusionsA single application of PDT to residual pockets provided a modest improvement of CAL and PPD over 3 months. Application of adjunctive PDT may lead to faster resolution of residual pockets and may be recommended for periodontal patients with slower healing capacity.     

Aluminium salt-based antiperspirant coated prosthesis liners do not suppress local sweating during moderate intensity exercise in hot and temperate conditions

ObjectiveTo determine whether coating prosthesis liners with a 5% aluminium zirconium tetrachlorohydrate antiperspirant solution (AZCH) reduces local sweating on the thigh.DesignDouble-blinded counter-balanced crossover designMethodsFourteen able-bodied participants (age: 28 ± 5 y; body mass: 73.9 ± 7.9 kg, height: 1.73 ± 0.09 m; peak oxygen consumption [VO_2peak]: 50.7 ± 9.1 mlO₂⋅ kg⁻¹⋅ min⁻¹) simultaneously wore a prosthesis liner on each leg, one treated with AZCH and one untreated, for four days prior to running at 50% of VO_2peak for 60 min in a temperate (23.7 ± 0.7 °C and 42.2 ± 2.6% relative humidity) or hot (34.0 ± 1.6 °C and 40.8 ± 6.1% relative humidity) environment. Rectal temperature (T_re) and whole-body sweat rates (WBSR) were measured to characterize thermal strain. Local sweat rate (LSR) was measured bilaterally underneath the liners, continuously, and heat-activated-sweat gland density (HASGD) was measured bilaterally every 15 min.ResultsIn temperate condition, the mean change in T_re was 1.2±0.4 °C and WBSR was 723 ± 129 g⋅ h⁻¹, whereas in the hot condition, change in T_re was 1.2±0.5 °C and WBSR was 911 ± 231 g⋅ h⁻¹. In the temperate condition, AZCH treatment did not alter LSR (treated: 0.50±0.17 mg·cm^–2 min^–1, untreated: 0.50±0.17 mg·cm^–2 min^–1; P = 0.87) or HASGD (treated: 54±14 glands·cm^–2, untreated 55±14 glands·cm^–2; P = 0.38). In the hot condition, AZCH treatment paradoxically increased LSR (treated: 0.88 ± 0.38 mg·cm^–2 min^–1, untreated: 0.74 ± 0.28 mg·cm^–2 min^–1; P = 0.04) but not HASGD (treated: 52 ± 17 glands·cm^–2, untreated: 48 ± 19 glands·cm^–2; P = 0.77).ConclusionThese results indicate coating prosthesis liners with 5% AZCH is ineffective at reducing local sweating.     

In vitro evaluation of adhesion/proliferation of human gingival fibroblasts on demineralized root surfaces by toluidine blue O in antimicrobial photodynamic therapy

BackgroundAntimicrobial photodynamic therapy (aPDT) in Dentistry has important effects as bacterial destruction in areas with periodontal disease. Some dyes applied in aPDT could present low pH and, consequently, result in tooth demineralization. This study evaluated demineralization produced by aPDT with toluidine blue O (TBO) at low pH and analyzed adhesion/proliferation of human gingival fibroblasts (HGF).MethodsIn the 1st phase, bovine enamel and root dentin fragments received 2 treatments: PDT4 group (TBO–100 μg/ml—pH 4–60 s) plus laser (660 nm, 45 J/cm², 1.08 J, 30 mW, 30 s, spot 0.024 cm², 1.25 W/cm², sweeping, non-contact) and CA group (citric acid plus tetracycline—pH 1–180 s). Surface hardness loss and tooth wear were statistically analyzed (Student’s t test, ANOVA/Tukey, p < 0.05). In the 2nd phase, human dentin fragments were divided in C (control group—scaling and root planing), PDT4 and CA. HGF (10⁴, 5th passage) were cultured on these fragments for 24, 48 and 72 h and counted in scanning electron microscopy photographs. Number of HGF was analyzed using repeated-measures ANOVA and Tukey (p < 0.05).ResultsPercentage of surface hardness loss was similar in dentin for PDT4 (71.5%) and CA (76.1%) (p > 0.05) and higher in enamel for CA (68.0%) compared to PDT4 (34.1%) (p < 0.05). In respect to wear, no difference was found between PDT4 (dentin: 12.58 μm, enamel: 12.19 μm respectively) and CA (dentin: 11.74 μm and enamel: 11.03 μm) (p > 0.05). Number of HGF was higher after 72 h in CA group (2.66, p < 0.05) compared to PDT4 (2.2) and C (1.33).ConclusionPDT4 is not as aggressive as CA for enamel. However, dentin demineralized promoted by PDT4 does not stimulate HGF adhesion and proliferation as CA.     

Gonarthritis photodynamic therapy with chlorin e6 derivatives

BackgroundThe new methods of osteoarthritis treatment are in constant demand due to the complexity of the early diagnosis and therapy. Specific features of Сhlorin e6 derivative (Ce6) accumulation in knee joint tissues and the efficiency of photodynamic therapy (PDT) of gonarthritis were studied.MethodsThe experimental research was conducted on the model of posttraumatic gonarthritis on rabbits. The analysis of dynamics of change of Ce6 concentration in tissues of a knee joint was carried out by the method of fluorescent diagnostics. The intra-joint PDT was carried out using 662 nm laser with energy density of 120–150 J/cm² and a sapphire diffuser. An analysis of slices was conducted to confirm the anti-inflammatory effect through apoptosis.ResultsThe method of fluorescent spectroscopy revealed that the highest amount of Ce6 was accumulated in the synovial membrane of a damaged knee joint 2.5 h after its intravenous introduction. On 14th day after gonarthritis modeling but before PDT the synovial membrane showed signs of synovitis. On 21st day after PDT the synovial membrane possessed noticeable villous structure, and no cells of inflammatory nature were observed.ConclusionFluorescent diagnostics in knee joint tissues can be used in clinical practice of gonarthritis before, during and after PDT for monitoring the Ce6 accumulation and for treatment control. Optimal radiation energy density was determined to be 150 J/cm². In the studied time intervals (5–25 min) no dependency of PDT effect on irradiation time at the same energy density was observed. The analysis of results of clinical and morphological research shows that PDT is a low-invasive method of gonarthritis treatment with a high degree of efficiency and selectivity.     

In vitro effects of photodynamic therapy induced by chloroaluminum phthalocyanine nanoemulsion

BackgroundThe photodynamic therapy (PDT) has been used to treat cancer mainly by inducing oxidative stress. Our aim was to evaluate the effect of PDT and its combination with methoxyamine (MX), a blocker of base excision repair (BER), in cells expressing high levels of the APE1 protein, which is involved in cell oxidative damage response.MethodsThe HeLa and A549 cells were treated for 3 h with chloroaluminum phthalocyanine incorporated into a well-designed nanoemulsion (ClAlPc/NE); and then irradiated by visible light (@670 nm) with doses of 0.1, 0.5 and 1.0 J/cm². A simultaneous combination of MX + ClAlPc/NE was performed and then irradiated with the selected dose of 0.5 J/cm². The treatments were evaluated in terms of viability, clonogenicity, DNA fragmentation, and cell death mechanism by apoptosis and/or necrosis.ResultsThe APE1 protein expression observed was higher in HeLa than in A549. Both cell lines exhibited substantial differences in cell cytotoxicity. The PDT decreased the clonogenicity of HeLa by inducing apoptosis (sub-G1 and annexin detection). Additionaly, the MX potentiates the PDT-effects in HeLa. Otherwise, low cytotoxicity was observed in A549 cells.ConclusionThe PDT induced apoptosis in high APE1 expressive HeLa cells, and the blockage of BER by MX increased its effects.     

Does supplemental photodynamic therapy optimize the disinfection of bacteria and endotoxins in one-visit and two-visit root canal therapy? A randomized clinical trial

AimTo evaluate the effectiveness of supplemental photodynamic therapy (PDT) in optimizing the removal of bacteria and endotoxins from primarily infected root canals after one-visit and two-visit treatments.MethodologyTwenty-four primarily infected root canals with apical periodontitis were selected and randomly divided into one-visit (n = 12) and two-visit treatment groups (n = 12). Chemo-mechanical preparation (CMP) was performed by using the single-file reciprocating technique + 2.5% NaOCL and a final rinse with 17% EDTA. The photosensitizer agent (methylene blue 0.1 mg/mL) was applied to root canals for 60 s before application of laser with a potency of 60 mW and energy density of 129 J/cm² for 120 s after CMP in the one-visit treatment and after 14-day inter-appointment medication with Ca(OH)₂ + Saline solution (SSL) in the two-visit treatment. Samples were collected before and after root canal procedures. Endotoxins were quantified by chromogenic limulus amebocyte lysate assay. Culture techniques were used to determine bacterial colony-forming unit counts.ResultsBacteria and endotoxins were detected in 100% of the initial samples, with median values of 1.97 × 10⁵ CFU/mL and 24.983 EU/mL, respectively. The CMP using single-file reciprocating technique was effective in the reduction of bacteria and endotoxins (All, p < 0.05). The supplemental PDT was effective in reducing bacterial load in the one-visit (p < 0.05) but not in the two-visit treatment after use of Ca(OH)₂ medication for 14 days (p > 0.05). In the two-visit group, after 14 days of inter-appointment medication with Ca(OH)₂, a significant reduction in the median levels of endotoxins was found in comparison to CMP alone (from 1.041 to 0.094 EU/mL) (p < 0.05). Despite the type of treatment, the supplemental PDT was not effective against endotoxins (p > 0.05).ConclusionsThe photodynamic therapy optimized the disinfection of bacteria from root canals in one-visit but not for two visit treatment modality with the accomplishment of calcium hydroxide medication. Despite the type of treatment, the supplemental PDT was not effective against endotoxins.     

Photodynamic therapy: An option in mycosis fungoides

BackgroundPhotodynamic therapy (PDT) is a well-known and effective treatment for non-melanoma skin-cancer. Numerous studies have also shown its effectiveness in mycosis fungoides. The aim of the study was to analyse MF patients treated with PDT at the Dermatology Unit of Bologna University.MethodsWe retrospectively analysed MF patients treated with PDT over the last ten years. Each PDT protocol consisted of the appliance for 3 h under an occlusive film dressing on each lesion of a one-mm-thick layer of 16% methyl aminolaevulinate (MAL) 160 mg/g cream (Metvix^®, Galderma, Paris, France). The cream was then removed and the skin was exposed to 630 nm red light from a diode lamp (Aktilite^®, Galderma Benelux, Rotterdam, the Netherlands), with a total radiation dose of 37 J/cm2 for 9 mins. A protocol of one session every month was scheduled. The treated lesions were clinically examined, before each treatment.ResultsFour cases, three male and one female, had been treated with PDT. Two patch lesions on the plantar area, one leg and the pubic area were treated. The number of PDT sessions ranged from 4 to 9. Two complete remissions and two partial remissions were observed. A low-to-mild burning sensation was reported during the treatment, and persisted over the next day; no further side effects were observed.ConclusionsOur series shows that PDT can be considered an effective second-line treatment in patients characterised by a disease located in difficult-to-treat anatomical areas such as the feet and the pubic area.     

Methylene blue,curcumin and ion pairing nanoparticles effects on photodynamic therapy of MDA-MB-231 breast cancer cell

PurposeThe aim of current study was to use methylene blue-curcumin ion pair nanoparticles and single dyes as photosensitizer for comparison of photodynamic therapy (PDT) efficacy on MDA-MB-231 cancer cells, also various light sources effect on activation of photosensitizer (PS) was considered.MethodIon pair nanoparticles were synthesized using opposite charge ions precipitation and lyophilized. The PDT experiments were designed and the effect of PSs and light sources (Red LED (630 nm; power density: 30 mW cm⁻²) and blue LED (465 nm; power density: 34 mW cm⁻²)) on the human breast cancer cell line were examined. The effect of PS concentration (0–75 μg. mL⁻¹), incubation time, irradiation time and light sources, and priority in irradiation of blue or red lights were determined.ResultsThe results show that the ion pairing of methylene blue and curcumin enhance the photodynamic activity of both dyes and the cytotoxicity of ion pair nanoparticles on the MDA-231 breast cancer cell line. Blue and red LED light sources were used for photo activation of photosensitizers. The results demonstrated that both dyes can activate using red light LED better than blue light LED for singlet oxygen producing.ConclusionNano scale ion pair precipitating of methylene blue-curcumin enhanced the cell penetrating and subsequently cytotoxicity of both dyes together.     

Streptococcus mutans photoinactivation using a combination of a high potency photopolymerizer and rose bengal

BackgroundLong treatment periods to reach a substantial inactivation of microorganisms are one of the critical challenges in the photodynamic therapy field.MethodsPlanktonic suspensions of Streptococcus mutans were treated in different groups: presence of rose bengal (RB at 2 μM) and light exposure by a new high potency photopolymerizer (L at wavelength = 440–480 nm; dosimetry = 96 J/cm² – 40 s of irradiation; potency density = 1200 mW/cm²; dosage = 48 J) – RB+L+ (PDT), just with dye – RB+L−, just with light – RB−L+ and absence of light and dye RB−L− (control group). Aliquots of each group were transferred to Petri dishes to colony counting (CFU/mL) with the data transformed in log₁₀. The results were submitted to ANOVA and Tukey test at 5%.ResultsPDT group presented total eradication of microorganisms showing statistical difference with all the other groups (5.82 log reduction ≅ 99%).ConclusionThe high potency photopolymerizer in pulsed emission at an extra short irradiation and low concentration of rose bengal could be considered as a progressive alternative to the control of S. mutans suspensions.     

Treatment of peritoneal carcinomatosis with photodynamic therapy: Systematic review of current evidence

BackgroundPeritoneal carcinomatosis results when tumour cells implant and grow within the peritoneal cavity. Treatment and prognosis vary based on the primary cancer. Although therapy with intention-to-cure is offered to selective patients using cytoreductive surgery with chemotherapy, the prognosis remains poor for most of the patients. Photodynamic therapy (PDT) is a cancer-therapeutic modality where a photosensitiser is administered to patients and exerts a cytotoxic effect on cancer cells when excited by light of a specific wavelength. It has potential application in the treatment of peritoneal carcinomatosis.MethodsWe systematically reviewed the evidence of using PDT to treat peritoneal carcinomatosis in both animals and humans (Medline/EMBASE searched in June 2017).ResultsThree human and 25 animal studies were included. Phase I and II human trials using first-generation photosensitisers showed that applying PDT after surgical debulking in patients with peritoneal carcinomatosis is feasible with some clinical benefits. The low tumour-selectivity of the photosensitisers led to significant toxicities mainly capillary leak syndrome and bowel perforation. In animal studies, PDT improved survival by 15–300%, compared to control groups. PDT led to higher tumour necrosis values (categorical values 0–4 [4 = highest]: PDT 3.4 ± 1.0 vs. control 0.4 ± 0.6, p < 0.05) and reduced tumour size (residual tumour size is 10% of untreated controls, p < 0.001).ConclusionPDT has potential in treating peritoneal carcinomatosis, but is limited by its narrow therapeutic window and possible serious side effects. Recent improvement in tumour-selectivity and light delivery systems is promising, but further development is needed before PDT can be routinely applied for peritoneal carcinomatosis.